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What ARE Turmeric and Curcumin? |
Turmeric is a spice obtained
from the dried root rhizomes of Curcuma longa, a
medicinal plant from the ginger family of
herbs, the Zingiberaceae. The rhizomes are dried and crushed in order to produce a yellow-orange powder. The biologically active compound
within this powder is curcumin, one of the most studied
phytochemicals in science. Turmeric powder contains
2% to 8% curcumin, which
we isolate to 95% standardized medicinal extract for research and nutritional supplementation. |
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What are the health properties of Curcumin? |
"Over 10,000 research papers and over 1000 review articles have
been published to discuss the molecular basis of curcumin’s
attributed antioxidant, anti-inflammatory, antibacterial,
antiapoptosis, anticancer, and antiaging activities." -
Stem Cells Translational Medicine | 2024
"Distinguished by its unique molecular structure, curcumin
exhibits potent biological activities including
anti-inflammatory, antioxidant, and potential anticancer
effects. The research points towards curcumin’s growing
importance as a multi-faceted natural compound in the medical
and scientific community. In the realm of contemporary science,
curcumin has sparked considerable interest due to its potential
health benefits. Studies have delved into its effectiveness
against chronic illnesses such as cancer, Alzheimer’s disease,
heart diseases, and inflammatory conditions. This interest is
fueled by its properties as an antioxidant, anti-inflammatory,
and role in cancer prevention. Scientists are examining how
curcumin influences various cellular processes by interacting
with multiple signaling molecules, including growth factors,
cytokines, and the genes involved in cell life cycle and
division. In summary, curcumin, with its deep-rooted history in
traditional healing practices and its promising prospects in
modern medical research, continues to be an area of keen
scientific focus. As research progresses to elucidate the
complexity of its chemistry and the breadth of its
pharmacological actions, curcumin stands as a key player in the
treatment of a diverse spectrum of health conditions." -
International
Journal of Molecular Sciences | 2024
"Curcumin is one of the most powerful natural
anti-inflammatories in existence." -
Curcumin in Alzheimer’s Disease and Depression | 2024
"Intensive studies carried out within the past 3 decades
confirmed that the anti-inflammatory and antitumor properties of
turmeric are attributable to its active component, curcumin.
Curcumin is a natural compound isolated from the rhizome of the
plant Curcuma longa (turmeric) that has been used to
treat inflammation, cancer and neurodegenerative diseases such
as multiple sclerosis (MS) and Parkinson’s disease. A large number of studies including both animal model
experiments and clinical trials, have verified the
anti-inflammatory and immunomodulatory properties of curcumin."
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Frontiers in Pharmacology | 2024
"Almost 7000 scientific papers on turmeric and almost 20,000
on curcumin have been published in PubMed. These studies
show that the golden spice has enormous health and medicinal
benefits for humans." -
Pharmacology
& Translational Science | 2023 |
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Where
to purchase Curcumin? |
Since 2000,
TURMERIC-CURCUMIN.COM has
offered Curcumin 95% extract
supplements to research institutions, physicians, and university medical centers. Quality control tests, laboratory analysis
certification, and rigorous
cGMP manufacturing
standards all ensure freshness, potency, and purity of contents. Orders are shipped
FedEx
or USPS Priority Air for fast and secure delivery. Contact
support@turmeric-curcumin.com
for bulk ordering, private
labeling, contract manufacturing or any other questions. Multiple bottle orders
will receive increasing quantity discounts listed below. Case purchases (12
bottles) will also
receive free US shipping. |
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200
capsules per bottle,
500
mG
OF Curcumin
95%
per capsule.
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Our label clearly
indicates the
contents (curcumin
extracted from turmeric root),
purity (95% standardized),
amount
per capsule (500mg) and number of
capsules per bottle (200). Each 12-bottle case contains
over 2.6 lbs (1.2 kg) of curcumin 95% turmeric root extract.
Since 2000, the geographical source of our curcumin
extract is turmeric grown in India. Within India, we are
extensively networked with selected farms in the
Eastern Ghats highlands, known for
turmeric with the highest natural
curcumin
content in the world, at 8.8%
and
the West Jaintia Hills district of Meghalaya, India, where Lakadong
turmeric is one of the world's finest with a curcumin content of
about 7.5%. From this high quality
turmeric (Curcuma
longa) root, we extract curcumin to a minimum 95%
concentration. Within this extraction is the full spectrum of curcuminoids -
curcumin, demethoxycurcumin, and bisdemethoxycurcumin - in their
natural composition ratio of 76:19:5 for maximum potency. This is the
same extract
used
in clinical trials and medical studies,
free of added chemicals, treatments, unknown "formulas",
"complexes" or "proprietary blends" which do not even disclose
how much of each ingredient the product contains. Our supplement
contains just two active ingredients; 500mg Curcumin 95% and 5mg
of Piperine.
You will receive a
100% natural, additive-free product.
There are no
synthetics, no starch, no sugars or sweeteners, no artificial colors or flavors, no sodium, no soy,
no yeast, no wheat, no corn, no rice or other grains, no gluten, no dairy, no preservatives, no
gums, no dyes, and no GMO.
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What is the suggested usage?
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"For optimal pharmacological effects, an oral dose of more than
8.0 grams per day is often required. Numerous clinical studies
demonstrated that a daily intake of 12 grams of curcumin is well
tolerated and safe." -
Pharmaceutics |
2024
"Researchers concluded that if you want to receive the maximum benefits
from curcumin, 30 mg per kilogram is the most effective dose." -
Molecular Neurobiology | 2024
"Curcumin's protective effect is
proportional to the dose, and the efficacy may be further
increased at a concentration of more than 200 mg per kg. Results
indicated that the efficacy of curcumin improved with higher
administered doses within the concentration range of 200 mg per
kg. The results from the fitted curves suggest that efficacy may
further improve at concentrations exceeding 200 mg/kg." -
Cardioprotective Effects of Curcumin Against Diabetic
Cardiomyopathie | 2024
"In a study on curcumin treatment
of drug-resistant tumor cells, a low dose of curcumin showed no
effect on antioxidant proteins, whereas a high dose resulted in
the inhibition of antioxidant proteins. Furthermore, high-dose
curcumin treatment has been reported to exacerbate the effects
on damaged mitochondria. This results in mitochondrial and DNA
damage and subsequent activation of the cell death pathway,
providing possible approaches for cancer therapy." -
Oncology Letters | 2024
"A study used two
dosages (2000 mg and 4000 mg) of curcumin powder daily for 30
days in 40 participants, aiming to decrease procarcinogenic
factors. Only the higher dose group showed a 40% reduction in
these foci, correlating with a significant increase in plasma
curcumin levels." -
Curcumin in
Cancer and Inflammation | 2024
"Curcumin
supplementation in doses of 3000 mg/day over 8–12 weeks showed
reductive effect on total cholesterol levels, however curcumin
therapy with doses less of 1000 mg per day has had no
significant effect." -
Complementary Therapies in Medicine Volume | 2024
"The US Food and Drug Administration
has permitted curcumin's safety. Because of multiple medical
research on the safety and harmfulness of curcumin, a tolerable
dosage of 4 – 8 grams per day is regarded to achieve the best
therapeutic results" -
Food and Agricultural Immunology | 2023
"The dose-dependent action of curcumin observed in our results
highlights the importance of considering its concentration in
cancer treatment. We found that increasing concentrations of
curcumin led to a proportional decrease in cell viability,
migration, and invasion in gastric cancer cells. This suggests
that the efficacy of curcumin in inhibiting cancer cell
progression is influenced by its dose, with higher
concentrations resulting in more pronounced effects. The
dose-dependent response may be attributed to curcumin's complex
interactions with multiple cellular targets and signaling
pathways. At lower concentrations, curcumin may predominantly
target specific pathways, while higher concentrations may engage
multiple pathways, leading to a more potent inhibitory effect."
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Dose-Response | 2023 |
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how are "curcumin"
products deceptively marketed and advertised?
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When selecting a
curcumin extract product, it is important to know the difference
between curcumin and turmeric.
Turmeric
root
contains only 3%
curcumin on average.
Consumers may be misled by deceptive marketing to believe there
is more curcumin per capsule than there actually is.
Unfortunately, these deceptions are not uncommon in the supplement
industry today:
HeartWise Inc., doing business as NatureWise, was hit with a
class action lawsuit for falsely advertising that its
dietary supplements contain “2250 mg Per Day” of curcumin,
when each pill actually only contains 750 mg. Plaintiff
Martha Valentine says the dietary supplement actually
requires three capsules to provide the advertised 2250 mg
dosage. She maintains that she was led to believe each of
the 180 capsules in the container contains 2250mg of the
curcumin supplement after reading and relying on the
product’s label that represented “2250 mg Per Day” of
curcumin and “180 vegetarian capsules.” She says that at the
time of her purchase, she did not know the product required
her to take three capsules to reach the full dosage of 2250
mg of curcumin, and if she had known the truth regarding
NatureWise’s misrepresentations and omissions, she would not
have purchased the product. She maintains that this
representation led her to believe that each of the capsules
contained 2250 mg of the curcumin supplement. However, upon
closer inspection of the bottle, NatureWise reveals that
three capsules must be consumed to provide the 2250 mg per
day serving. NatureWise’s misleading representations and
omissions lead consumers to pay a premium for the
supplements because they falsely believe that they are
receiving three times as much curcumin as they actually
receive in each bottle. “NatureWise intentionally fails to
adequately disclose to consumers that more than one capsule
is required to obtain the labeled dosage amount. Defendant
knew and intended that consumers would purchase, and pay a
premium for, a supplement labeled as having a 2250 mg of
curcumin per day, leading consumers to believe that by
taking 1 capsule per day they would be able to get all the
benefits of consuming a large dosage of curcumin." -
Valentine et al v. HeartWise Inc. d/b/a NatureWise and
HeartWise Wonder Inc., Case No. 20-cv-4302, N.D. Cal.
Sam’s West Inc's Member’s Mark
supplements was hit with a class action lawsuit on March 23, 2023 in a Tennessee federal court
for falsely advertising its turmeric curcumin complex
health supplement. According to the lawsuit filed by
plaintiff Matthew Casella, the product’s
front label representations say it contains 500 mg of
“standardized extract” of “turmeric curcumin complex” and
the Supplement Facts on the back label specify that “95%
Standardized Turmeric (Curcuma longa) Extract” was used.
These representations give consumers the impression the
product contains 95% (475mg) of curcuminoids per serving,
Casella says. “However, lab testing conducted by ConsumerLab.com revealed that instead of the expected 475
mg, the product contains only 9.7 mg of curcuminoids per
serving,” he alleges. The ingredients list states that “CurcuWIN
Turmeric Extract” is the extract used, however a report from
ConsumerLab found that “CurcuWin is only 20% curcuminoids.”
If the product contains CurcuWIN, as listed in the
ingredients, the extract cannot also be “95% Standardized
Turmeric (Curcuma longa) Extract,” as listed in the
supplement facts, Casella reasons. “As a result of the false
and misleading representations, the product is sold at
premium price.” -
Matthew Casella, et al. v. Sam’s West Inc., Case No.
3:23-cv-00102, in the U.S. District Court for the Eastern
District of Tennessee.
"Doctor's Curcumin" on the front of the label,
but the details confirm that each capsule is 100% turmeric
spice.
"Turmeric
Curcumin 500mg Enhanced Formula"
only contains 200mg Curcumin extract, and the remainder is 300mg turmeric.
"1000mg Super Complex Curcumin (25%)" is actually
just 250mg of Curcumin extract and the
remaining 750mg is turmeric.
"Turmeric
Curcumin Proprietary Blend 1000mg" but
contains only 50mg Curcumin 95%
extract per capsule, or 3,000mg per bottle (60 capsules x
50mg) and yet is priced higher than our bottle, which
contains a total of 100,000mg of Curcumin 95% extract.
"Premium Turmeric Curcumin
Complex Plus 1500" contains 150mg of Curcumin and 600mg of turmeric spice
per serving, and the serving size is two capsules, meaning
only 75mg of Curcumin 95% extract per capsule.
Actual labels from
"Curcumin" bottles:
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does piperine improve absorption, enhance
bioavailability, and work synergistically with Curcumin?
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"The association with piperine, an alkaloid derived from black
pepper (Pipernigrum L), is capable of increasing the
bioavailability of some drugs by inhibiting intestinal and
hepatic glucuronidation. In humans, administration of 20mg of
piperine with 2g of curcumin increased its bioavailability by
2000% compared to administration of 2g of curcumin alone. When
curcumin (20 and 40mg/kg) was co-administered with piperine
(bioavailability enhancer) at a dose of 2.5mg/kg, its
pharmacological effects were intensified. Piperine is capable of
increasing absorption, plasma concentration, and bioavailability
of curcumin in both rats and humans without significant side
effects. The administration of 20mg/kg of piperine with 2g/kg of
curcumin in rats increases its bioavailability by 154% compared
to administration of 2g/kg of curcumin alone. Piperine is a
non-specific drug metabolism inhibitor, with low discrimination
between different forms of cytochrome P-450. In rats, orally
administered piperine strongly inhibits the hepatic activity of
aryl hydrocarbon hydroxylase (AHH) and UDP-glucuronyl
transferase, with a potent inhibitory effect on pharmacological
metabolism." -
Curcumin in Alzheimer’s Disease and Depression: Therapeutic
Potential and Mechanisms of Action | 2024
"Curcumin and piperine supplementation applied before and after
exercise positively affects the muscle damage of athletes after
exercise." -
Examination of the effect of curcumin supplementation on liver
enzymes and some physiological parameters in volleyball players
| 2024
"The bioavailability of curcumin can be enhanced by piperine (an
alkaloid derived from black pepper). Using piperine combined
with curcumin significantly increased serum levels of curcumin
in humans and animals by 2,000 times because of the extensive
absorption and bioavailability." -
The Use of Curcumin in the Treatment of Colorectal, Breast,
Lung, and Prostate Cancers: An In Vivo study Update | 2024
"When analyzed in humans, 2 grams of isolated curcumin
showed undetectable or very low serum levels. After the
concomitant administration of 20 mg of piperine, an increase in
concentrations was observed within the time frame of 0.25 to 1
hour after administration. In those rats in which piperine
pre-administration was performed before receiving curcumin,
there was a significant increase in the oral bioavailability of
curcumin, especially at 6 hour after piperine administration.
Piperine, when administered concomitantly with 2 grams of
curcumin in healthy human volunteers, increased the curcumin
bioavailability by 2000%. Curcumin and piperine supplementation
for obese mice under caloric restriction may increase the loss
of body fat and suppresses HFD-induced inflammation." -
Antioxidants |
2024
"Both curcumin and piperine suppress proliferation of
leukemia cells and their IC50 value has reported to be 30 μM and
25 μM, respectively. These anti-cancer agents have capacity of
inducing apoptosis in leukemia cells via mitochondrial pathway.
Besides, curcumin and piperine induce autophagy and mediate S
arrest.The current section clearly demonstrated that curcumin
and its combination with other therapies can suppress leukemia
progression." -
Journal of Herbal Medicine, The Effects of Curcumin on
Neurodegenerative Diseases: a Systematic Review | 2024
"To improve the bioavailability of curcumin, one of the
potential strategies is adding piperine when administering
curcumin orally. Piperine also has antioxidant,
immunomodulatory, and anti-inflammatory activities. Piperine can
increase the in vivo bioavailability of curcumin by
inhibiting its metabolism and reducing the required dose of
curcumin in the clinical setting. Piperine binds to several
areas of the enzyme to form a hydrogen bond complex with
curcumin that can increase its bioavailability up to twenty
times." -
Vitamin D
and Curcumin Piperine Attenuates Disease Activity and Cytokine
Levels in Systemic Lupus Erythematosus Patients | 2024
"Studies have shown that combining curcumin with piperine, a
compound found in black pepper, can increase its bioavailability
by inhibiting metabolism." -
PLoS One | January 2024
"Black pepper (Piper nigrum) family piperaceae,
with the main active ingredient piperine, has a hypoglycemic
effect (Panda & Kar, 2003). Turmeric (Curcuma longa),
family Zingiberaceae, in which a vital active ingredient is
curcumin, has been revealed to have hypoglycemic, antioxidant,
and lipid-lowering effects in many investigational studies (Khaliq
et al., 2015). Earlier studies revealed that both herbs work in
synergy in lowering postprandial blood glucose levels It was
hypothesized that black pepper and turmeric together have a
greater effect on lowering postprandial glycemia." -
A
Review on the Extraction Process and Therapeutic Activity of
Curcumin on Diabetes Mellitus and Cancer | 2024
"Piperine enhances bioavailability when combined with
curcumin in a complex. This was connected previously with 2000%
increase in curcumin bioavailability. Several organic compounds
have also been utilized to boost curcumin bioavailability, the
majority of which reduce the metabolism of curcumin and enhance
its absorption. Most of these compounds were developed to slow
down the metabolism of curcumin and improve its bioavailability.
Piperine, the primary active component of black pepper, is the
most widely used." -
Biomedicine & Pharmacotherapy | 2024
"Piperine
has been found to increase the bioavailability of curcumin
significantly. Curcumin (oral, 1 g/d plus piperine 10 mg/day for
12 weeks) reduced cardiovascular risk and enhanced antioxidant
capacity in type 2 diabetes mellitus through decreasing serum
levels of total cholesterol and non-HDL-cholesterol." -
Pharmacological Research | 2023
"Piperine increased the bioavailability of curcumin by
154%. Curcumin combined with piperine exhibited higher
intestinal absorption (78%). When co-administered with piperine,
the half-life of curcumin was increased from 12.8h to 28.9h.
Co-administration of piperine (20 mg/kg) and curcumin (2 mg/kg)
increased the plasma concentration of curcumin in a short time,
i.e. within 1-2h, peak time was increased, elimination half-life
decreased, and clearance decreased. In humans, even with a
2g load of curcumin, the serum level was undetectable. A higher
extent of absorption and higher bioavailability of curcumin
(2000%) was observed in humans using 20mg piperine." -
Review of Curcumin and Its Different Formulations:
Pharmacokinetics, Pharmacodynamics and
Pharmacokinetic-Pharmacodynamic Interactions | 2023
"Piperine is known to enhance curcumin absorption and tissue
uptake, while also reducing curcumin hepatic metabolism. Once
absorbed, curcumin is metabolized within the epithelial cells
and/or effluxed back into the intestinal lumen. This efflux is
thought to occur due to the presence of efflux transporters
within the intestinal cell membranes. Piperine from black
pepper, as well as certain catechins from green tea, are able to
inhibit these transporters, thus increasing the amount of
curcumin that remains in the body. A preclinical study
administrated an orally delivered powder of curcumin (2
g/kg/day) and piperine (20 mg/kg/day) and concluded that
piperine significantly increases the serum concentration of
curcumin, resulting in a 154% improvement in its relative
bioavailability. Similarly, a clinical study conducted with the
combined oral administration of curcumin and piperine dissolved
in water (2 g of curcumin powder, 20 mg of piperine and 150 mL
of water). The study found that piperine significantly increased
the serum concentration of curcumin, resulting in a relative
bioavailability increase of 2000%" -
Effect of Curcumin Consumption on Inflammation and Oxidative
Stress in Patients on Hemodialysis: A Literature Review | 2023
"The bioavailability of curcumin was significantly increased
by 2000% when piperine, which is extracted from black pepper,
was also taken as a supplement." -
Effect of
Curcumin and Coenzyme Q10 Alone and in Combination on Learning
and Memory in an Animal Model of Alzheimer’s Disease | 2023
"Piperine is an adjuvant that can greatly improve
bioavailability of curcumin. Piperine slows the metabolism of
curcumin by inhibiting hepatic and intestinal glucuronidation.
Previous studies have shown that administering curcumin with
piperine can increase serum concentrations of curcumin by up to
2000%, indicating that glucuronidation inhibition may be the
major mechanism of increasing curcumin bioavailability. As such,
the formulation of the supplement administered in the current
study, 1,400 mg of curcumin and 10 mg of piperine, may have
helped to increase serum concentrations of curcumin such that it
could exert its biological action." -
Frontiers in Nutrition, Sport and Exercise Nutrition | 2023
"The study has found that curcumin (oral, 1 gram per day
plus piperine 10 mg/day for 12 weeks) reduced cardiovascular
risk and enhanced antioxidant capacity in T2DM through
decreasing serum levels of TC, non-HDL-c and MDA, while also
increasing serum adiponectin, SOD or HDL-C levels." -
Pharmacological Research | 2023
"The combination of curcumin with piperine has better
gastrointestinal absorption and reduces curcumin's systemic
excretion. Piperine increases the bioavailability of curcumin by
binding to the enzyme glucuronidase in the intestine, preventing
glucuronidation and reducing the excretion of curcumin from the
stool" -
The effect of curcumin-piperine on cardiometabolic, inflammatory
and oxidative stress factors and macular vascular density | 2023
"Curcumin + piperine decreased waist circumference, systolic
blood pressure, total cholesterol, low-density
lipoprotein-cholesterol, fasting blood glucose, alanine
transaminase and aspartate transaminase compared with placebo.
Curcumin + piperine may be considered as an adjunct therapy to
improve anthropometric measures, blood pressure, lipid profile,
blood glucose, and liver function in Non-alcoholic Fatty Liver
Disease patients." -
Efficacy of
curcumin plus piperine co-supplementation in moderate-to-high
hepatic steatosis | 2023
"Curcumin-piperine
supplementation for 12 weeks resulted in significant reductions
in serum levels of total cholesterol, triglycerides, weight,
waist circumference, and systolic and diastolic blood pressure
in patients. To improve pharmacokinetic features,
co-administration of curcumin with piperine has been introduced
as an alternative. Piperine, which is a naturally occurring
alkaloid from pepper, has been shown to increase the
bioavailability of curcumin and reduce its glucuronidation." -
The effects of curcumin-piperine supplementation on
inflammatory, oxidative stress and metabolic indices in patients
with ischemic stroke in the rehabilitation phase: a randomized
controlled trial | 2023
"Recent studies
demonstrated that piperine potentiates curcumin’s inhibitory
effect on tumor progression via enhancing its delivery and
therapeutic activity. Among the numerous candidates tested so
far, curcumin, piperine and certain types of cannabinoids
performed promisingly well in colon carcinoma models as
monotherapy agents. Piperine, a dietary polyphenol isolated from
black and long peppers, distinguished with its intrinsic
features, improves not only curcumin’s existing anti-cancer
activity, but also its extremely poor bioavailability. As a
single agent, piperine alone also displays anti-mutagenic and
anti-tumor activities." -
Frontiers in Pharmacology | 2023
"Several
studies done by using curcumin in conjunction with various
anticancer compounds, as in piperine...have shown significant
suppression, reduction/inhibition of IL-6, IL-1β, IL-19, TNF-α
and COX-2 (Al-Dossari et al., Citation2020; X. Q. Hu et al.,
Citation2016; Neyrinck et al., Citation2013; Tremmel et al.,
Citation2019; Yan et al., Citation2019)." -
Curcumin: recent updates on gastrointestinal cancers | 2023
"Black pepper piperine is one of the most effective boosters
of curcumin bioavailability. The simultaneous administration of
curcumin and piperine to humans or animals boosted the serum
levels by more than a thousandfold. Piperine contained in black
pepper can improve the uptake of curcumin by 2,000% (20 times).
The vast metabolism of turmeric in the hepatic tissues and
intestinal walls increased its bioavailability, which improved
through piperine. Taking these two substances with an oil rich
in unsaturated fatty acids further strengthens this benefit.
Zeng et al. examined the effect of piperine pre-administration
on oral curcumin bioavailability. In this investigation, rats
were given 20 mg/kg piperine first, followed by 200 mg/kg
curcumin at intervals of 0.5–8 h after piperine treatment. The
pre-treatment with piperine before curcumin administration
significantly increased curcumin oral bioavailability in all
tested rats. Recent research suggests that oral administration
of curcumin and piperine for symptomatic COVID-19 therapy might
dramatically reduce mortality and morbidity (53). The
conjugation between piperine and curcumin may be a safe and
natural option for preventing post-COVID symptoms." -
Impacts of turmeric and its principal bioactive curcumin on
human health: Pharmaceutical, medicinal, and food applications:
A comprehensive review | 2023
"The combination
of Curcumin with piperine was associated with a 2000%
improvement in Curcumin bioavailability." -
Health Science Reports | 2023
"Another
promising approach is the simultaneous administration of
curcumin with piperine, an alkaloid from black pepper and long
pepper. Piperine significantly increases the bioavailability of
curcumin—up to 2000%—by preventing its metabolism." -
An Overview
of the Enhanced Effects of Curcumin and Chemotherapeutic Agents
in Combined Cancer Treatments | 2023
"Curcumin has
received worldwide attention for its multiple health benefits,
which are best achieved when curcumin is combined with agents
such as piperine to increase its bioavailability significantly.
Pawar et al reported that the administration of oral curcumin
with piperine as symptomatic adjuvant therapy in COVID 19
treatment could substantially reduce morbidity and mortality and
ease the logistical and supply related burdens on the healthcare
system. Askari et al reported that 46 outpatients with COVID 19
disease were randomly allocated to receive two capsules of
curcumin - piperine for 14 days. There was a significant
improvement in dry cough, sputum cough, ague, sore throat,
weakness, muscular pain, headache and dyspnoea in curcumin -
piperine groups. Kumar et al reported that using curcumin, Piper
Nigrum Piperine and catechin could cure and prevent COVID 19
outbreaks and infection. Curcumin and piperine interact and form
a π–π intermolecular complex, which enhances curcumin's
bioavailability." -
Therapeutic potential of curcumin in ARDS and COVID 19 | 2023
"Curcumin by itself has very low bioavailability due to
ineffective absorption, and fast metabolism and excretion. This
issue can be solved by combining curcumin with piperine (a key
active ingredient in black pepper) to create a curcumin complex
that is readily absorbed and metabolized in the body. Curcumin
is more active when combined with piperine to provide major
health benefits. These benefits are maximized when curcumin is
coupled with agents such as piperine, that significantly
increase its bioavailability." -
The Therapeutic Role of Curcumin in Inflammation | 2023
"Curcumin has received worldwide attention for its multiple
health benefits, which appear to act primarily through its
anti-oxidant and anti-inflammatory mechanisms. These benefits
are best achieved when curcumin is combined with agents such as
piperine, which increase its bioavailability significantly." -
Department of Nutrition, Central Michigan University | 2023
"Coadministration of piperine and curcumin enhances the oral
bioavailability of curcumin, and thereby, its therapeutic
efficacy. It has been proved that piperine can increase the
delivery of curcumin to systemic circulation due to its ability
to improve the pharmacokinetic profiles of curcumin. Piperine
was reported to increase the bioavailability of oral curcumin:
154% and 2000% increase in curcumin concentration in the plasma
was observed in rats and humans, respectively. The increased
concentration of curcumin in the bloodstream is due to the
ability of piperine to decrease the rate of metabolism of
curcumin in the intestine and liver. In the intestine, piperine
regulates membrane lipid dynamics and inhibits the intestinal
metabolism of curcumin, leading to enhanced curcumin retention
in the intestine. Furthermore, piperine reduces the rate of
curcumin metabolism in the liver. In addition, curcumin and
piperine interacted synergistically, reducing proinflammatory
mediators. The combination also demonstrated better
compatibility profiles with neuronal cells. Curcumin and
piperine significantly ameliorate inflammation. Curcumin and
piperine synergistically attenuate inflammatory response
in-vitro. The curcumin-piperine combination at the highest dose
exhibited significantly lesser expression of pro-inflammatory
cytokines compared to the individual treatment at respective
concentrations. Curcumin-piperine combination showed better
compatibility with neuronal cells compared to individual
treatments. The combination of curcumin and piperine
synergistically interacts in suppressing pain. Curcumin and
piperine interacted synergistically, suppressing inflammatory
mediators with favorable compatibility with neuronal cells. The
combination of curcumin and piperine elicited a greater
antinociceptive effect compared to that of either curcumin or
piperine alone." -
CM Journal | 2022
"Curcumin-piperine supplementation led to fewer
thromboembolic episodes following recovery from COVID-19
infections." -
Effectiveness of Curcumin on Outcomes of Hospitalized COVID-19
Patients: A Systematic Review of Clinical Trials, Nutrients |
2022
"The combination of curcumin and piperine
had synergistic additive effects. Furthermore, the combination
of piperine and curcumin can enhance the bioavailability of
curcumin in human and animal models.The absorption,
distribution, metabolism, excretion, and toxicity of a
therapeutic could be achieved by combining with bioenhancers
like piperine." -
Evidence-Based Complementary and Alternative Medicine | 2022
"The most common way to increase curcumin’s poor
pharmacokinetic profile is the combination of curcumin with the
natural alkaloid of black pepper—piperine (Piper nigrum) that is
a strong inhibitor of glucuronidation process. This formulation
resulted in 3-fold increase of curcumin concentrations, as
compared to pure curcumin, when 5 mg of piperine was added to 2
g of curcumin." -
Curcumin in Ulcerative Colitis - Current Overview, Nutrients |
2022
"Piperine can increase the uptake of
curcumin. The most important findings of this study were the
administration of curcumin associated with piperine can inhibit
the elevation of plasmatic levels of some cytokines. This result
shows the capacity of curcumin to modulate an inflammatory
response acutely induced by exercise. The anti-inflammatory
action of curcumin associated with piperine prevented the
expression of inflammatory cytokines. Supplementation of 500
mg curcumin with piperine for seven days
was able to inhibit the inflammatory response after an
experimental protocol of running on a treadmill until voluntary
fatigue." -
The
Curcumin Supplementation with Piperine Can Influence the Acute
Elevation of Exercise-Induced Cytokines: Double-Blind Crossover
Study, Biology | 2022
"Studies have shown that
using higher oral doses of curcumin results in appropriate
levels of curcumin necessary for clinical activity.
Coadministration with piperine, an extract of black pepper or
with lecithin can enhance solubility, and the former can
increase plasma bioavailability by up to 2000%." -
A Review
On Curcuma Longa Effect On Human Health, Journal of Emerging
Technologies and Innovative Research | 2022
"Piperine behaves as a bio-enhancer and inhibits
drug-metabolizing enzymes to aid curcumin absorption and
bioavailability. It has numerous pharmacological effects and
some health benefits, particularly against chronic diseases
(decrease in insulin resistance, anti-inflammatory properties,
amelioration of hepatic steatosis. Shoba et al. reported that
curcumin bioavailability improved by 2000% at 45 min after
concomitant orally administrated piperine." -
Molecules | 2022
"A study examined the
effects of curcumin combined with piperine (from black pepper
extract used to improve the bioavailability of curcumin) as an
add-on to the ongoing antipsychotic treatment. At the end of 16
weeks, both groups showed significant improvements in total
scores and general psychopathology subscale of the Positive and
Negative Syndrome Scale (PANSS). Both the doses were tolerated
well without much adverse effects." -
Role of Curcumin in the Management of Schizophrenia: A Narrative
Review | 2022
"Improvement in weakness was
more in the curcumin-piperine group than with placebo group.
Conclusion: The present study results showed that
curcumin-piperine cosupplementation in outpatients with COVID-19
could significantly reduce weakness." -
The efficacy of curcumin-piperine co-supplementation on clinical
symptoms, duration, severity, and inflammatory factors in
COVID-19 outpatients: a randomized double-blind,
placebo-controlled trial, Trials | 2022
"For
centuries, turmeric containing curcumin and Piper nigrum
containing piperine have been used as food additives and folk
medicine, including Traditional Chinese Medicine. Curcumin and
piperine have been shown to interact synergistically in various
preclinical pharmacological studies. Many recent studies
reported synergistic effects of curcumin and piperine
combination in various pharmacological models, including lung
cancer, aging, and hepatocellular carcinoma. Pharmacodynamically,
the combination of curcumin and piperine could simultaneously
inhibit multiple sites of action in the pain pathway. The
ability of curcumin and piperine to modulate diverse pathways of
pain could lead to robust inhibition of pain transmission when
those are coadministered." -
CM Journal | 2022
"Piperine, an alkaloid
responsible for the pungency of black pepper, dramatically
increases the serum levels of curcumin in rats and humans." -
Protective
Effects of Curcumin in Cardiovascular Diseases - Impact on
Oxidative Stress and Mitochondria, Cells | 2022
"Piperine together with curcumin could improve its
bioavailability and make its anti-epileptic action even more
effective." -
New
Promising Therapeutic Avenues of Curcumin in Brain Diseases, Molecules
| 2022
"Piperine (found in black
pepper) increases your body's ability to hold onto curcumin by
up to 2,000%. Piperine slows down the metabolization of
turmeric's active compound, leaving it available for your body
to absorb. If you're going the supplement route, it's best to
choose options that also contain piperine to improve the
potential effects." -
The Untold Truth Of Turmeric, Mashed | 2022
"Curcumin + piperine treatment was associated with a significant
reduction in the mean serum levels of immunoglobulin E (IgE).
Curcumin plus piperine might have positive effect on serum
immunoglobulin E (IgE) levels." -
Effects of curcumin-piperine supplementation on systemic
immunity in young women | 2022
"There is evidence that the
combination of piperine in black pepper with curcumin in
turmeric increases the bioavailability of curcumin by 2000% and
inhibits the intestinal and hepatic glucuronidation of
curcumin." -
Curcumin-Rich Curry Consumption and Neurocognitive Function from
4.5-Year Follow-Up of Community-Dwelling Older Adults, Nutrients
| 2022
"Bioavailability enhancer
curcumin-piperine considerably increased the curcumin blood
levels." -
Role of Curcumin in Retinal Diseases, Clinical and Experimental
Ophthalmology | 2022
"One pilot study concluded
that an oral dosage of 500 mg of curcumin with piperine
could restore lipid peroxidation in patients suffering from
tropical pancreatitis." -
A Comprehensive Review on the Therapeutic Potential of
Curcuma longa in Relation to its Major Active Constituent
Curcumin, Frontiers in Pharmacology | 2022
"Piperine, a bio-enhancer improves the absorption of curcumin.
Of note, piperine (10 mg/day) was used to increase the
bioavailability of curcumin." -
An Update on the Exploratory Use of Curcumin in Neuropsychiatric
Disorders, Antioxidants | 2022
Archived studies on curcumin and piperine |
|
|
HAS THE SAFETY OF CURCUMIN
95%
BEEN ESTABLISHED?
|
The safety, tolerability, and
nontoxicity of curcumin at high doses has been well
established by human clinical trials.
The
US FDA classifies Turmeric as
GRAS (Generally
Recognized As Safe). Preclinical
and clinical studies indicate that curcumin is well tolerated
and the overwhelming safety profile of curcumin is evident.
Before using any herbs or dietary supplements in amounts greater
than usually found in foods, consult a health care provider.
"Clinical studies have shown that curcuminoids, including
curcumin, bisdemethoxycurcumin, and demethoxycurcumin, have
safety characteristics at daily doses of 4000–8000 mg at 95%
concentration. The US Food and Drug Administration (FDA) has
given curcumin the " generally recognized as safe" (GRAS)
designation. Various studies have shown that curcumin is safe,
well-tolerated, and useful in the prevention and treatment of a
variety of chronic diseases, such as cancer, heart disease,
diabetes, neurological disorders, skin conditions, liver
complications, and infectious diseases." -
Biomedicine & Pharmacotherapy | 2024
"Long-term studies have shown that curcumin is safe and
protective when used in the diet. In one study, high doses of
curcumin (8 g/day) do not cause side effects. In another study,
curcumin was administered at doses up to 12 g/day for three
months with no apparent toxicity." -
Review of the Protective Mechanism of Curcumin on Cardiovascular
Disease | 2024
"As
an antioxidant, anti-infection, anti-inflammatory, and
anti-tumor compound, curcumin has been approved by the United
States Food and Drug Administration as a safe compound." -
Molecular Neurobiology | 2024
"Curcumin has been demonstrated to be safe even when it is
administered at high doses. A phase 1 human trial in which as
much as 8000 mg of curcumin per day was administered for 3
months to patients with high-risk or premalignant lesions
reported no toxic effects. No serious side effects were reported
in RA patients receiving 500 mg of curcumin per day over a
period of 8 weeks. Curcumin treatment has no obvious toxic
effect on liver or kidney functions; therefore, curcumin is
generally recognized as a safe compound by the U.S. Food and
Drug Administration." -
Frontiers in Pharmacology | 2024
"The European Food Safety Authority (EFSA) established
an acceptable daily intake of curcumin at 3 mg/kg body weight.
For optimal pharmacological effects, an oral dose of more than
8.0 g/day is often required. Numerous clinical studies
demonstrated that a daily intake of 12 g of curcumin is well
tolerated and safe." -
Pharmaceutics |
2024
"Curcumin has been used as a dietary supplement for centuries
and is considered pharmacologically safe." -
International Journal For Multidisciplinary Research | 2024
"A series of authoritative international institutions, such as
the Food and Drug Administration (FDA) in the USA and the Joint
FAO/WHO Expert Committee on Food Additives, have confirmed the
safety of curcumin in daily use and clinical treatment." -
Toxics | 2023
"According to the Joint Nations and World Health Organization
Expert Committee on Food Additives (JECFA), curcumin is regarded
as a safe chemical and is hence appropriate for everyday dietary
usage and can be taken by patients of any age for a longer
period of time without experiencing any negative side effects."
-
Biomedicine |
2023
"Curcumin is one of the most promising anticancer agents as it
combines high biological safety for normal cells/tissues with
potent cytotoxic activity against various human cancers." -
International Journal of Molecular Sciences | 2023
"According to the US Food and Drug Administration (FDA) report,
curcumin has been considered as “Generally Recognized as Safe”
(GRAS) even at doses between 4000 and 8000 mg/day" -
Evidence-Based Complementary and Alternative Medicine | 2023
"The safety of curcumin and turmeric products has been confirmed
by the Food and Drug Administration (FDA), the Food and
Agriculture Organisation (FAO) and the World Health Organisation
(WHO). Curcumin has shown a very promising safety profile.
According to reports by JECFA (Joint Expert Committee on Food
Additives of the United Nations and the World Health
Organisation) and EFSA (European Food Safety Authority), the
acceptable daily intake (ADI) of curcumin is 0–3 mg/kg body
weight. Several studies in healthy volunteers have confirmed the
safety and efficacy of curcumin." -
An Overview
of the Enhanced Effects of Curcumin and Chemotherapeutic Agents
in Combined Cancer Treatments | 2023
"Curcumin has also been recognized as safe by the US Food and
Drug Administration (FDA). In most studies, very few adverse
effects or no severe adverse effects occurred with turmeric
extract and curcumin supplements, showing that it’s well
tolerated globally. None of the patients required rescue
medication for adverse effects management. Overall, the benefits
of Curcuma longa extract and curcumin supplementation
were significantly greater than their risks. Therefore, it can
be recommended for musculoskeletal conditions." -
Safety and Efficacy of Turmeric (Curcuma longa) Extract and
Curcumin Supplements in Musculoskeletal Health | 2023
"Curcumin has been shown to be safe in numerous human studies,
with only minor toxicity associated with this polyphenol.
Therefore, curcumin is increasingly being viewed as a
biomolecule capable of being administered for an extended period
without causing adverse effects. The findings of the current
study indicate that there were no significant adverse events
associated with the short term use of PPI and curcumin." -
BMJ British Medical Journal | 2023
"Curcumin is labeled as safe by the Food and Drug Administration
(FDA, USA), and has achieved therapeutic pursuit in treating
metabolic diseases, immune-related diseases, and cancer, owing
to its vast biological target and with practically no
aftereffects. Curcumin is an active natural compound that
exhibits therapeutic effects on different diseases, including
antiviral, antibacterial, anti-amyloid, thrombo-suppressive,
antiarthritic, antioxidation, anti-inflammatory, and anticancer,
with minimal aftereffects. Curcumin is safe in humans and has
chemopreventive and chemotherapeutic effects. In vitro
experimental evidence indicates that curcumin has excellent
anticancer ability and can target cancer via diverse mechanisms
by modulating several cellular signal pathways." -
Curcumin a
Natural Phenol and Its Therapeutic Role in Cancer | 2023
"Genotoxicity and mutagenicity assessments suggest that
curcumin extract does not induce DNA damage or mutations.
Furthermore, carcinogenicity studies demonstrate no evidence of
increased cancer risk associated with the curcumin extract." -
Department of Nutrition, Central Michigan University | 2023
"The Joint Food and Agriculture
Organization (FAO), World Health Organization (WHO) Expert
Committee on Food Additives (JECFA) and the European Food Safety
Authority (EFSA) allocated an acceptable daily intake (ADI) for
curcumin of 3 mg/kg body weight." -
Nutrients |
2022
"Curcumin is considered a safe
compound and authorized as a GRAS compound (generally recognized
as safe) by US FDA (United States Food and Drug Administration).
It is well tolerated at a higher dose of 12g in humans. Cells
treated with the curcumin-piperine combination at their EC90
concentration showed no toxicity to neuronal cells. Reduction in
locomotive behaviors was not observed with the curcumin-piperine
combination, indicating no potential CNS side effects of
curcumin-piperine combination at its highest therapeutic doses.
We found no effects of the combination on the spontaneous
locomotor activity at their high doses. The results indicate no
potential central nervous system (CNS) side effects of the
curcumin and piperine combination." -
CM Journal | 2022
"Curcumin is “generally recognized as safe” (GRAS) as a dietary
supplement by the U.S Food and Drug Administration (FDA) and the
European Food Safety Authority (EFSA) and has been catalogued
with the E100 code of the European Union." -
Curcumin: A
Novel Way to Improve Quality of Life for Colorectal Cancer
Patients? International Journal of Molecular Sciences | 2022
"According to the US Food and Drug Administration, curcumin is
classed as safe for both human consumption and pharmacological
purposes without any known side effects." -
Life |
2022
"Studies have shown that systemic exposure to
curcumin-containing products at doses of up to 8,000 mg/day was
safe and tolerable and did not cause serious adverse events." -
Curcumin (Curcuma, Turmeric) and Cancer, PDQ Integrative,
Alternative, and Complementary Therapies Editorial Board | 2022
"According to relevant clinical trials on
safety and toxicity, the acceptable dose of curcumin for maximum
efficacy is 4 – 8 grams per day. It has been reported that
humans can tolerate treatment with curcumin at a dose up to 12 grams
per day." -
Frontiers in Pharmacology | 2022
"The US Food and Drug Administration has marked curcumin as a
"By and large Recognized As Safe" item. The United Nations and
World Health Organization Expert Committee on Food Additives and
European Food Safety Authority suggested the everyday admission
of 0-3 mg/kg body weight of curcumin. Furthermore, curcumin
supplementation in a few clinical preliminaries exhibited
wellbeing profiles at dosages in the range of 4000 and 8000 mg/
day." -
Journal of Antimicrobial Agents, Prevention of Female
Reproductive Disorders with the Help of Curcumin | 2022
Archived studies on
the safety of curcumin |
|
Why NATURAL curcumin 95%
extract from turmeric root without nanoparticles or
other highly processed synthetic polysorbates and emulsifiers? |
"In the
last few years questions have been raised regarding the
potential toxicity of carbon nanotubes (CNTs) to humans and
environment. It is believed that the physico-chemical
characteristics of these materials are key determinants of CNT
interaction with living organisms, and hence determine their
toxicity." -
Determinants of carbon nanotube toxicity | 2023
"This
study evaluated the toxic events of curcumin nanoparticles with
alterable surface polarity in alveolar macrophages. In
conclusion, the cytotoxicity of curcumin nanoparticles on
alveolar macrophages is surface-charge dependent, which in turn
is associated to the uptake pathway and localization of curcumin
nanoparticles in cells." -
Toxicity of curcumin nanoparticles towards alveolar macrophage,
Food and Chemical Toxicology | 2022
"The
harmfulness of nanoparticles is impacted by their condition of
conglomeration and mechanical properties, which are reliant upon
their creation and decontaminating strategies. Worries about the
poisonousness of nanoparticle-based conveyance strategies
incorporate neuroinflammation, excitotoxicity, and unfavorably
susceptible responses." -
Alternative & Integrative Medicine | 2022
"Curcumin
nanomicelle suppressed spermatogenesis, increased
immunoreactivity of 8-oxodG, stimulated the Hsp70–2a and Hsp90
expressions, and resulted in severe DNA and mRNA damages.
Moreover, the curcumin nano-micelle received animals exhibited
remarkable reductions in the spermatozoa count, motility and DNA
integrity. In conclusion, chronic and high dose consumption of
curcumin nanomicelle results in remarkable oxidative stress." -
Curcumin nano-micelle induced testicular toxicity in healthy
rats; evidence for oxidative stress, Biomedicine &
Pharmacotherapy | 2021
"A number of
nanoparticles have negative impacts on male germ and somatic
cells which could ultimately affect fertility or the ability to
produce healthy offspring." -
Toxicity mechanisms of nanoparticles in the male reproductive
system | 2021
"Nanoparticles may act as
reproductive toxicants depending on several factors, and induce
damage to the male reproductive system by affecting the
seminiferous tubules and spermatogenesis. This is mainly due to
the fact that nanoparticles can easily enter the blood
circulatory system and reach the testes by crossing the blood
testes barrier. The bioaccumulation of nanoparticles in the
testes causes seminiferous tubule histopathology and severely
affects the sperm number, motility and morphology. Moreover,
nanoparticles also induce disturbances to the Leydig cells,
causing decline in the testosterone level with consequent
testicular injury and reduced sperm production." -
Perspectives of Nanoparticles in Male Infertility: Evidence for
Induced Abnormalities in Sperm Production | 2021
"Curcumin nanoparticles suppressed the proliferation of
testicular cell lines in vitro. In the
present study, we disclosed the acute damage on mouse
spermatogenesis and sperm parameters by nano-curcumin. Our
results suggested that the reproductive toxicity of
nanoformulated curcumin needs to be prudently evaluated before
its application." -
Acute Damage to the Sperm Quality and Spermatogenesis in Male
Mice Exposed to Curcumin-Loaded Nanoparticles, International Journal of
Nanomedicine | 2020
"Nanoparticles are able to pass
certain biological barriers and exert toxic effects on crucial
organs, such as the brain, liver, and kidney. Only recently,
attention has been directed toward the reproductive toxicity of
nanomaterials. Nanoparticles can pass through the blood–testis
barrier, placental barrier, and epithelial barrier, which
protect reproductive tissues, and then accumulate in
reproductive organs. nanoparticles accumulation damages organs
(testis, epididymis, ovary, and uterus) by destroying Sertoli
cells, Leydig cells, and germ cells, causing reproductive organ
dysfunction that adversely affects sperm quality, quantity,
morphology, and motility or reduces the number of mature oocytes
and disrupts primary and secondary follicular development. In
addition, nanoparticles can disrupt the levels of secreted
hormones, causing changes in sexual behavior. However, the
current review primarily examines toxicological phenomena. The
molecular mechanisms involved in nanoparticles toxicity to the
reproductive system are not fully understood, but possible
mechanisms include oxidative stress, apoptosis, inflammation,
and genotoxicity. Previous studies have shown that nanoparticles
can increase inflammation, oxidative stress, and apoptosis and
induce ROS, causing damage at the molecular and genetic levels
which results in cytotoxicity." -
Potential adverse effects of nanoparticles on the reproductive
system
"Recent studies have shown that
nanoparticles disturb the developing oocyte by invading the
protective barrier of theca cells, granulosa cell layers and
zona pellucida. Nanoparticles disrupt sex hormone levels through
the hypothalamic–pituitary-gonadal axis or by direct stimulation
of secretory cells, such as granule cells, follicle cells,
thecal cells and the corpus luteum. Some nanoparticles can cross
the placenta into the fetus by passive diffusion or endocytosis,
which can trigger fetal inflammation, apoptosis, genotoxicity,
cytotoxicity, low weight, reproductive deficiency, nervous
damage, and immunodeficiency, among others." -
Nanoparticles and female reproductive system: how do
nanoparticles affect oogenesis and embryonic development
"Females are particularly more
vulnerable to nanoparticle toxicity, and toxicity in this
population may affect reproductivity and fetal development.
Moreover, various types of nanoparticles have negative impacts
on male germ cells, fetal development, and the female
reproductive system." -
Toxicity of Nanoparticles on the Reproductive System in Animal
Models: A Review |
|
What are
the pharmacological actions of Curcumin? |
|
First shown to have
anti-bacterial activity in 1949, curcumin has
since been shown to have anti-inflammatory,
anti-oxidant, pro-apoptotic, chemopreventive,
chemotherapeutic, anti-proliferative, wound
healing, anti-nociceptive, anti-parasitic, and
anti-malarial properties as well. Numerous
clinical and preclinical studies and trials
evaluating curcumin's safety and efficacy have
revealed its potential against a wide range of human diseases
and ailments have been completed. These
pathologies include diabetes, obesity, neurologic and
psychiatric disorders, and cancer, as well as
chronic illnesses affecting the eyes, lungs,
liver, kidneys, and gastrointestinal and
cardiovascular systems. Curcumin has
also been shown to regulate numerous transcription
factors, cytokines, protein kinases, adhesion
molecules, redox status and enzymes that have
been linked to inflammation. Growing experimental evidence reveals that
curcumin exhibits multitarget biological
implications signifying its crucial role in
health and disease, with pharmacological effects
against numerous diseases like neuronal,
cardiovascular, metabolic, kidney, endocrine,
skin, respiratory, infectious, gastrointestinal
diseases and cancer. The ability of curcumin to
modulate the functions of multiple signal
transductions are linked with attenuation of
acute and chronic diseases.
Extensive research over the past
half century has shown that curcumin
(diferuloylmethane), a component of the golden
spice turmeric (Curcuma longa), can
modulate multiple cell signaling pathways.
Extensive clinical trials over the past quarter
century have addressed the pharmacokinetics,
safety, and efficacy of this nutraceutical
against numerous diseases in humans. Some
promising effects have been observed in patients
with various pro-inflammatory diseases including
cancer, cardiovascular disease, arthritis,
uveitis, ulcerative proctitis, Crohn’s disease,
ulcerative colitis, irritable bowel disease,
tropical pancreatitis, peptic ulcer, gastric
ulcer, idiopathic orbital inflammatory
pseudotumor, oral lichen planus, gastric
inflammation, vitiligo, psoriasis, acute
coronary syndrome, atherosclerosis, diabetes,
diabetic nephropathy, diabetic microangiopathy,
lupus nephritis, renal conditions, acquired
immunodeficiency syndrome, β-thalassemia,
biliary dyskinesia, Dejerine-Sottas disease,
cholecystitis, and chronic bacterial
prostatitis.
|
Curcumin has also shown protection against
hepatic conditions, chronic arsenic exposure, and alcohol intoxication.
Extensive preclinical
studies over the past three decades have indicated curcumin’s
therapeutic potential against a wide range of human diseases. In
addition, curcumin has been shown to directly interact with
numerous signaling molecules. These preclinical studies have
formed a solid basis for evaluating curcumin’s efficacy in
clinical trials. The clinical trials conducted thus far have
indicated the therapeutic potential of curcumin against a wide
range of human diseases. Curcumin has a potential to prevent
and/or manage various diseases due to its anti-inflammatory,
anti-oxidant and anti-apoptotic properties with an excellent
safety profile. In contrast, the anti-cancer effects of curcumin
are reflected due to induction of growth arrest and apoptosis in
various premalignant and malignant cells. Curcumin reduces the
risk of osteoporosis via amelioration of mitochondrial membrane
function, PKB phosphorylation, microRNA-365 activation,
osteoblasts proliferation. It reduced ulcerative colitis by
inhibiting neutrophil chemotaxis. The gastroprotective effect is
due to inhibition of acid release, amelioration of blood flow,
angiogenesis and collagenization of gastric tissue. Curcumin
shows hepatoprotective action due to inhibitory activity against
NF-jB. Additionally, curcumin reduced liver marker enzymes,
cholesterol levels and replication of hepatitis B and C viruses.
Curcumin treatment reduces asthma and allergy symptoms mainly
due to inhibition of histamine release, attenuation of IgE,
inhibition of COX-2 enzyme, suppression of JNK54/56, ERK 42/44
and p38 MAPK, stimulation of Nrf-2/HO-1 pathway, upregulation of
Notch1, Notch2 receptors, GATA3 etc. Curcumin blocks certain
cytokines and enzymes, inhibits ROS generation, downregulate
NF-kB activation, induce extracellular matrix production,
upregulate collagen and fibronectin expressions thereby reduce
inflammatory diseases. Curcumin treatment reduces fibronectin
and collagen IV expressions, suppresses TGF-bsignaling and
exhibits antioxidant, anti-inflammatory and anti-apoptotic
potential thereby ameliorates kidney functions. Studies have indicated the
anticancer effects of curcumin by evaluating its effect on a
variety of biological pathways involved in cell cycle
regulation, apoptosis, tumorigenesis, mutagenesis and
metastasis.
|
Curcumin mediates its effects
by modulation of various molecular targets including
transcription factors, enzymes, cell cycle proteins, receptors,
cell surface adhesion molecules, neurotransmitters etc. Curcumin
exhibits antioxidant, anti-inflammatory and anti-apoptotic
potential thereby reduce neurodegenerative, cardiovascular,
metabolic, gastrointestinal, respiratory and inflammatory
diseases. Clinical and preclinical data have conclusively proved
that curcumin modulates neurotransmitter levels and reduces
neurodegeneration thereby ameliorate neuronal and behavioral
dysfunctions. Curcumin reduces Alzheimer’s pathology by reducing
Abplaques and tau phosphorylation. The anti-depressant and
anxiolytic mechanism of curcumin includes inhibition of brain
MAO activity, modulation of serotonin receptor and amelioration
of neurotrophic factors. Curcumin reduces drug addiction and
withdrawal symptoms, possibly through modulation of HAT, DNA
methyl transferases, CREB, BDNF and CaMKIIalevels. Curcumin
administration reduced Huntington’s disease by reducing
huntingtin aggregates. In cardiovascular disease, the
anti-atherosclerotic mechanism of curcumin includes the
inhibition of platelet aggregation and modulation of cholesterol
homeostasis. Curcumin effectively reduce hypertension by
blocking angiotensin I receptor, reducing circulating
angiotensin-converting enzyme and inducing vasodilation. The
antiarrhythmic mechanisms of curcumin are due to modulation of
Ca 2þ homeostasis and blockade of potassium channels.
The
anti-fungal mechanisms of curcumin includes the leakage of
intracellular component, disruption of plasma membrane,
generation of oxidative stress, induction of apoptosis,
inhibition hyphae development, upregulation of chitin synthase
and PKC etc. Curcumin treatment downregulated genomic
transcription and translation, inhibited viral oncoproteins,
suppressed the Akt/SREBP-1 pathway, inhibited hemagglutination,
proteases, integrase and Tat protein acetylation resulting in
antiviral effects. Curcumin
administration reduces cerebral infracts size and volume during
stroke. During metabolic diseases, curcumin treatment
ameliorates b-cell dysfunction, insulin signaling and GLP-1
secretion while reduces glucose intolerance, hyperglycemia,
hyperinsulinemia and hyperlipidemia.
|
|
|
|
what studies and
research papers on
Curcumin have been published in medical literature and scientific journals? |
March 2024
Curcumin for
COVID-19: 26 studies from 225 scientists and 14,736 patients in
10 countries
c19curcumin.com | March 2024
Curcumin reduces risk for COVID-19 with very high confidence for
mortality, hospitalization, recovery, and in pooled analysis,
high confidence for viral clearance. Statistically significant
improvements are seen for mortality, hospitalization,
progression, recovery, and viral clearance. Statistically
significant improvements are seen for mortality, ventilation,
hospitalization, progression, recovery, and viral clearance. 16
studies from 14 independent teams in 6 different countries show
statistically significant improvements in isolation (9 for the
most serious outcome). Meta analysis using the most serious
outcome reported shows 45% improvement. Results are similar for
Randomized Controlled Trials, similar after exclusions, and
similar for peer-reviewed studies. Other meta analyses for
curcumin can be found showing significant improvements for
mortality, hospitalization, recovery, and symptoms.
Cytotoxic evaluation of curcumin and quercetin in
MCF-7 cell lines World Journal of Biology
Pharmacy and Health Sciences | March 2024 Curcumin, a
naturally occurring compound found in turmeric, has been
extensively studied for its potential anticancer properties,
including its effects on MCF-7 cell lines. MCF-7 cells are
commonly used as a model for studying breast Anti-Inflammatory
Effects: Both curcumin and quercetin possesses anti-inflammatory
properties, and chronic inflammation is often associated with
cancer development. By reducing inflammation, curcumin may
indirectly contribute to the cytotoxic effect on cancer cells.
In this study, the cytotoxic potential of a curcumin was found
to be greater than the cytotoxic potential of quercetin in the
individual testing, however the phyto nutrient combination &
natural extracts of both curcumin and quercetin shows the better
cytotoxic potential in the MCF7 Breast cancer cell line. The
combination of both the phytoconstituents shows an effective
synergistic effect that can elicit a powerful cytotoxic response
on the breast cancer cells. The synergistic effects observed in
the combination of curcumin and quercetin on MCF-7 cells suggest
that the compounds may act through complementary mechanisms,
enhancing their individual anticancer activities.
Impact of Curcumin on Aging: Manifestations and
Limitations Curcumin and Neurodegenerative
Diseases | March 2024 Due to its potential for treating
cancer and Alzheimer’s disease, turmeric, which contains
curcumin, has gained considerable attention in recent years. The
primary reason why curcumin is effective is its
anti-inflammatory properties. Age-related redox imbalance
results in overexpression of reactive oxygen species levels.
Curcumin reduces oxidative stress associated with cellular
senescence and can benefit aging individuals.
Exploring the molecular mechanism of action of
curcumin for the treatment of diabetic retinopathy, using
network pharmacology, molecular docking, and molecular dynamics
simulation Integrative Medicine Discovery |
March 2024 A wide range of pharmacological properties have
been attributed to curcumin, including antioxidant,
anti-inflammatory, antimutagenic, etc. Researchers found that
curcumin had a beneficial effect on the expression of vascular
endothelial growth factor (VEGF), tumor necrosis factor-alpha
(TNF-α), and pro-inflammatory cytokines in the retina of
diabetic rats. In addition, curcumin has also been demonstrated
to have the capability of slowing down or even reversing the
progression of certain fundus diseases, making it a new option
for the treatment of retinal diseases. As a result of this
study, curcumin may exert a role in the treatment of diabetic
retinopathy through multi-target and multi-pathway regulation,
which indicates a possible direction of future research. In
summary, through network pharmacology, molecular docking, and MD
simulations, the present study investigated the potential
mechanisms of curcumin in the treatment of diabetic retinopathy.
Following its introduction into the body, curcumin has multiple
targets and pathways for treating diabetic retinopathy. Several
targets were shown to be used by curcumin to exert anti-diabetic
retinopathy effects, including AKT1, IL-1B, IL-6, ALB, and
TNF-α, and regulating several signaling pathways such as
PI3K-Akt signaling pathway, lipid and atherosclerosis signaling
pathway, and AGE-RAGE signaling pathway in diabetic
complications.
Curcuma longa: A Natural Ally in Alzheimer’s Disease
Management Curcumin and Neurodegenerative
Diseases | March 2024 Curcuma longa, commonly known
as turmeric or saffron, contains a compound called curcumin that
possesses potential biopharmacological activity. Curcumin is
considered safe by the American Food and Drug Administration
(FDA) and does not exhibit any side effects when consumed in
moderate amounts. Numerous studies have been conducted on
curcumin due to its therapeutic potential in various diseases,
particularly in neurodegenerative disorders such as Alzheimer’s
disease. Research indicates that this substance holds remarkable
potential as an effective and safe treatment.
Curcumin activates the JNK signaling pathway to
promote ferroptosis in colon cancer cells
Chemical Biology & Drug Design | March 2024 Recent evidence
has proved that curcumin as a natural polyphenol has anticancer
and anti-proliferative effects in cancer cells. Curcumin
suppressed SW-480 cancer cells viability in dose-dependent
manner. Cell treatment with curcumin led to accumulation of ROS
and iron within cells and increase in the intracellular levels
of lipid peroxidation. In addition, curcumin modulated the mRNA
and protein expression levels of ferroptosis-related proteins
including ACSL4, GPx4 and FTH1 and suppression of JNK signaling.
Curcumin may exhibit its anticancer effect on colorectal cancer
by downregulating JNK signaling to induce ferroptosis in SW-480
cells.
Longevity and anti-aging effects of curcumin
supplementation GeroScience | March 2024
Curcumin demonstrated a positive impact on slowing down the
aging process by postponing age-related changes. Curcumin may
have anti-aging properties by changing levels of proteins
involved in the aging process, such as sirtuins and AMPK, and
inhibiting pro-aging proteins, such as NF-κB and mTOR. In
clinical research, this herbal compound has been extensively
examined in terms of safety, efficacy, and pharmacokinetics.
There are numerous effects of curcumin on mechanisms related to
aging and human diseases.
Curcuminoids with Antineurodegenerative Properties:
Current Trends and Future Perspectives
Curcumin and Neurodegenerative Diseases | March 2024
Curcuminoids are bioactive compounds found in Curcuma longa
Linn. (Zingiberaceae), a species commonly known as turmeric or
turmeric root, widely used in traditional medicine for
centuries. Recent research has demonstrated the potential of
these metabolites as antineurodegenerative agents, substances
that can help prevent or treat neurodegenerative diseases such
as Alzheimer’s disease, Parkinson’s disease, and multiple
sclerosis. Studies have focused on understanding the molecular
mechanisms by which curcuminoids exert their
antineurodegenerative properties, as well as developing more
effective and bioaccessible formulations of these compounds to
improve their bioavailability and ability to cross the
blood–brain barrier. Additionally, research has explored the
combination of curcumin with other substances or therapies, such
as combining them with other natural compounds, conventional
drugs, or non-pharmacological therapies like deep brain
stimulation.
Curcumin protects mice with myasthenia gravis by
regulating the gut microbiota, short-chain fatty acids, and the
Th17/Treg balance Heliyon | March 2024
Curcumin modified the gut microbiota composition, increased
microbial diversity, and, in particular, reduced
endotoxin-producing Proteobacteria and Desulfovibrio levels in
T-AChR-induced gut dysbiosis. Moreover, we found that curcumin
significantly increased fecal butyrate levels in mice with T-AChR-induced
gut dysbiosis. In addition, curcumin repressed the increased
levels of lipopolysaccharide (LPS), zonulin, and FD4 in plasma.
Curcumin enhanced Occludin expression in the colons of MG mice
induced with T-AChR, indicating dramatically alleviated gut
permeability. Furthermore, curcumin treatment corrected T-AChR-induced
imbalances in Th17/Treg cells. Curcumin modifies gut microbiota
composition and increases the abundance of SCFA-producing
bacteria. Curcumin reduced FD4 concentrations as well as LPS and
zonulin levels in serum. Curcumin supplementation
increased the level of butyrate and regulated the TH17/Treg
balance. Curcumin is an effective constituent of the
traditional Asian medicine turmeric with antioxidant,
anti-inflammatory and neuroprotective properties. Of note,
curcumin has been recently proposed for the management of
neurological diseases by regulating the gut microbiota and
improving gut barrier function. It was reported that curcumin
could considerably alter the ratio of pathogenic and beneficial
bacteria by reducing the relative abundance of genera including
Prevotellaceae, Coriobacterales, Enterobacteria, and
Enterococci while increasing the relative abundance of
favorable genera including Bifidobacteria and
Lactobacilli. Hence, curcumin seems to have promising
clinical applications. We found that curcumin alleviated the
clinical symptoms, corrected the microbiota imbalance, increased
SCFA-producing bacteria, reduced intestinal permeability, and
regulated the Th17/Treg balance in T-AChR-induced MG mice.
Considering the protective effect of curcumin on the gut
microbiota and the regulation of immune responses by SCFAs, we
evaluated the concentrations of SCFAs in the feces by using
GC‒MS. In the T-AChR-induced EAMG group, fecal acetic acid and
butyric acid concentrations were decreased, whereas curcumin
administration reversed this reduction. These changes may be
directly correlated to the abundance of the genera
Oscillospira, Akkermansia, and Allobaculum.
Curcumin has been proven to be neuroprotective and
anti-inflammatory in both humans and animals; furthermore,
curcumin is used to treat Huntington's disease, Alzheimer's
disease, and cerebral ischemia.According to our study, curcumin
alleviated the clinical symptoms of MG mice, which was
consistent with previous reports. In addition, curcumin altered
the gut microbiota composition, increased SCFA-producing
bacteria, reduced intestinal permeability, and regulated the
Th17/Treg balance of T-AChR-induced MG mice. Curcumin and
its metabolites have been demonstrated to affect the gut
microbiota. Our findings have revealed that curcumin could
restore the original gut microbial composition in T-AChR-induced
MG mice and increase the abundance of a few important bacterial
species. However, the disorders of the gut microbiota during
EAMG were restored after treatment with curcumin, which mainly
manifested as an increase in gut microbial diversity and
richness. Consistently, curcumin increased the frequency of CD4+
CD25+ Foxp3+ Tregs and decreased the frequency of CD4+ IL-17A+
Th17 cells in spleens and inguinal lymph nodes. This shows that
curcumin has the ability to restore the imbalance of Th17/Treg
cells in T-AChR-induced MG mice. As a result, the host's immune
system contributes to the beneficial effects.
Curcumin Promotes Diabetic Foot Ulcer Wound Healing
by Inhibiting miR-152-3p and Activating the FBN1/TGF-β Pathway
Molecular Biotechnology | March 2024 Curcumin has been used
as a traditional remedy for inflammation and wound healing, and
it works at diverse stages, such as inflammation, maturation,
and proliferation, thereby accelerating the entire process of
wound healing. Studies have shown that curcumin treatment can
cause fibroblasts to infiltrate into the wound site and
accelerate wound healing. In addition, curcumin has been found
to be beneficial for diabetic foot ulcer and may be a
potential candidate for treatment. Curcumin inhibited the
apoptosis of fibroblasts, promoted their migration ability, and
alleviated the damage of fibroblasts stimulated by HG.
Furthermore, curcumin treatment promoted angiogenesis and
accelerated wound healing in diabetic foot ulcer rats.
This suggests that curcumin plays an important role in the
process of alleviating diabetic foot ulcer. According to
previous studies, there are many miRNAs involved in the
treatment of different diseases by curcumin. Studies have shown
that curcumin can attenuate vascular calcification through the
exosomal miR-4b-92p/KLF3 axis, and curcumin therapy protects
PC12 cells from high glucose-induced inflammatory responses.
Curcumin alleviates the progression of diabetic foot ulcer
by inhibiting miR-152-3p. In summary, curcumin activates
the FBN1/TGF-β pathway by inhibiting miR-152-3p, thereby
inhibiting HG-induced fibroblast apoptosis, promoting fibroblast
proliferation and migration, alleviating HG-induced fibroblast
damage, and promoting angiogenesis in diabetic foot ulcer
rats, thereby accelerating wound healing in diabetic foot
ulcer rats. This provides a new theoretical basis for curcumin
treatment of DFU and may become a potential therapeutic target
for diabetic foot ulcer.
Cardioprotective Effects of Curcumin Against
Diabetic Cardiomyopathies: A Systematic Review and Meta-Analysis
of Preclinical Studies Traditional and
Western Medicine Center for Cardiovascular | March 2024
Meta-analysis showed that curcumin significantly improved
cardiac function indices, decreased markers of myocardial
injury, HW/BW ratio and randomized blood glucose compared to the
control group, in addition to showing beneficial effects on
mechanistic indices of myocardial oxidation, inflammation,
apoptosis, and autophagy. Curcumin may exert cardioprotective
effects in DCM through its antioxidant, anti-inflammatory,
autophagy-enhancing, and anti-apoptotic effects. Modern studies
have shown that curcumin can attenuate damage in DCM by being
anti-inflammatory(Wei et al., 2023), anti-oxidative stress(Wu et
al., 2022), anti-apoptosis(Ren et al., 2020), modulation of
autophagy(Sadeghi et al., 2023), and anti-fibrotic(Wang et al.,
2022). thus, curcumin emerges as a potential cardioprotective
candidate for ameliorating DCM. Our results suggest that
curcumin may play a cardioprotective 486 role in DCM through its
antioxidant, anti-inflammatory, autophagy-enhancing, and
anti-apoptotic effects.
Curcumin inhibits prostate cancer by upregulating
miR-483-3p and inhibiting UBE2C Journal of
Biochemical and Molecular Toxicology | March 2024 Evidence
has shown the efficacy of curcumin in inhibiting the progression
of prostate cancer. In this research, curcumin was found
to suppress the proliferation and enhance the apoptotic rate in
in vitro prostate cancer cell models in a dose- and
time-dependent manner. In humans, the expression levels of
UBE2C are significantly higher in prostate cancer versus
benign prostatic hyperplasia. Treatment with curcumin decreased
the expression of UBE2C, whereas it increased miR-483-3p
expression. In summary, curcumin exerts its antitumor effects
through regulation of the miR-483-3p/UBE2C axis by decreasing
UBE2C and increasing miR-483-3p. The findings may also provide
new molecular markers for prostate cancer diagnosis and
treatment.
Curcumin and turmeric extract inhibit SARS-CoV-2
pseudovirus cell entry and spike-mediated cell fusion
bioRxiv | March 2024 Our study shows that turmeric extract
and curcumin are potential inhibitors of SARS-CoV-2 infection at
entry points, either by direct or indirect infection models.
Curcumin has been tested for its anti-SARS-CoV-2 activities by
plaque assay in Vero cells. Using the original virus, curcumin
inhibits SARS-CoV-2 infection. Curcumin may inhibit SARS-CoV-2
viral replication as indicated by reduced N protein expression
following viral infection. Here, we showed that curcumin and TE
reduced PSV entry in331 293T/hACE2/TMPRSS2 cells, in which 10 μM
curcumin and 10 μg/ml TE significantly affected the number of
GFP dots. From the previous studies, Marin-Palma et al. reported
that 10 μM curcumin can inhibit SARS-CoV-2 infection in Vero E6
cells. It is also reported that curcumin inhibits SARS-CoV-2
infection at concentrations of 3-10 μM.28. Furthermore, curcumin
inhibited PSV339 entry in 293/hACE2 cells. These results
corroborate curcumin effects against SARS-CoV-2340 infection
with our data representing curcumin inhibition at PSV cell entry
point. It has been known that curcumin affects the early stages
of viral replication cycles, including viral-receptor
attachment, internalization, and fusion that have been studied
against several types of viruses which involve influenza,
dengue, zika, chikungunya, pseudorabies, and VSV. Moreover,
curcumin and TE inhibit secondary infection via cell-to-cell
transmission in a syncytia formation model mediated by
SARS-CoV-2 spike expression. Cells treated with curcumin and TE
showed smaller syncytia with fewer nuclei than control cells.
Curcumin can also interact with SARS-CoV-2 spike. These data
align with our results that curcumin inhibited PSV350 entry and
syncytia formation. Our in vitro study using PSV and syncytia
models revealed that both curcumin and TE are potential
inhibitors of SARS-CoV-2 infection. Curcumin can interfere with
the spike-receptor binding during direct viral or
intercellular transmission, hindering viral infection and cell
fusion.
Interleukin-4 from curcumin-activated OECs emerges
as a central modulator for increasing M2 polarization of
microglia/macrophage in OEC anti-inflammatory activity for
functional repair of spinal cord injury
Cell Communication and Signaling | March 2024
Curcumin, a bioactive polyphenol extracted from rhizome of the
Curcuma longa, possesses a variety of pharmacological and
biological effects properties, such as anti-inflammatory,
antioxidant, anticancer, immunomodulatory, autophagy-enhancing,
and anti-microbial, etc. [34,35,36,37,38]. In addition to the
reported benefits, numerous studies have shown that Curcumin
exerts distinct neuroprotective and neutrophic effects on
neuronal cells and glia by modulating their related signalling
pathways [39,40,41]. Noteworthy, several recent reports have
demonstrated that Curcumin can improve OEC proliferation,
migration, morphologic changes, secretion of neurotrophic
factors and phagocytic activity [29, 42]. That is, Curcumin
significantly enhance the activation of OECs. In this regard,
Curcumin potentiates the beneficial behavior of OECs including
anti-inflammation and immunomodulation. As a result, aOECs could
function as the most promising candidates for cell-based
transplantation therapy targeting the CNS injury and
neurodegenerative diseases.
Efficacy and safety of curcumin therapy for knee
osteoarthritis: A Bayesian network meta-analysis
Journal of Ethnopharmacology | March 2024 Compared with
placebo, curcumin significantly reduced the visual analogue
scale pain score and total WOMAC score. Compared with NSAIDs,
curcumin and curcumin + NSAIDs had a reduced incidence of
adverse reactions. The surface under the cumulative ranking
curve results indicated that curcumin monotherapy, curcumin +
chondroprotective agents, and curcumin + NSAIDs have good
clinical value in osteoarthritis treatment. Curcumin, either
alone or in combination with other treatments, is considered to
have good clinical efficacy and safety in osteoarthritis
treatment. Drug combinations containing curcumin may have the
dual effect of enhancing efficacy and reducing adverse
reactions. Curcumin has anti-inflammatory, antitumour,
antioxidant, lipid-regulating, anticoagulant and other
pharmacological effects (Benameur et al., 2023; Luo et al.,
2023; Moballegh Nasery et al., 2020; Zhang et al., 2018).
Curcumin is a bioactive natural substance with great potential
clinical application value and is widely used in traditional
Chinese medicine to treat osteoarthritis and rheumatoid
arthritis (Akaberi et al., 2021; Feng et al., 2022; Henrotin et
al., 2022). Curcumin has anti-inflammatory and analgesic effects
similar to those of NSAIDs for arthritis and has a lower
incidence of adverse reactions (Chopra et al., 2013). Curcumin
is believed to exert an anti-inflammatory effect by inhibiting
the biological activity and synthesis of important proteases
that mediate the inflammatory process, such as cyclooxygenase-2,
lipoxygenase and inducible nitric oxide synthase (iNOS) (Paulino
et al., 2016). In addition, curcumin is believed to protect
cartilage (Comblain et al., 2016; Liu et al., 2018). Prior to
the current work, some clinical studies preliminarily confirmed
the clinical efficacy of curcumin in the treatment of arthritis
(Atabaki et al., 2020; Jamali et al., 2020). There are also
traditional head-to-head meta-analyses in the literature that
provide further evidentiary support for treating arthritis with
curcumin (Feng et al., 2022; Wang et al., 2021). In terms of
reducing RM use, curcumin, curcumin + NSAIDs and NSAIDs are
better than placebo, and curcumin + NSAIDs are better than
NSAIDs alone. These results indicate that the use of curcumin
may reduce the total amount of analgesic drugs used by knee
osteoarthritis patients. In terms of the incidence of adverse
reactions, both curcumin and curcumin + NSAIDs were lower than
NSAIDs alone. The results found that curcumin, curcumin + CP,
and curcumin + NSAIDs have good clinical value in treating knee
osteoarthritis. The results of SUCRA indicate that the two best
treatment measures for reducing VAS pain scores are curcumin and
curcumin + CP. Curcumin and NSAIDs are the preferred options for
reducing the total WOMAC score. Curcumin + NSAIDs is the best
medication for reducing the use of RM. Curcumin + NSAIDs and
curcumin + CP are the best two drug regimens for reducing the
incidence of AE. The above results suggest that curcumin can not
only have better clinical efficacy in the treatment of knee
osteoarthritis but also reduce the incidence of AE by its
combination with NSAIDs, but this situation still needs more
clinical data for verification. The conclusion of this NMA will
provide a new perspective for clinical decision-making on the
use of curcumin in the treatment of KOA, and we believe that the
combination of curcumin with other drugs should be studied
further. Experimental research (Guan et al., 2022; Hamdalla et
al., 2022; Zhang and Zeng, 2019) suggests that curcumin has a
good effect in the treatment of knee osteoarthritis, which can
promote chondrocyte proliferation, inhibit chondrocyte
apoptosis, inhibit the destruction of inflammatory factors on
cartilage, and maintain the balance of the internal environment
of articular cartilage. Shakibaei et al. found that curcumin can
inhibit the expression of MMP-3 and MMP-9 induced by IL-1β/TNF-α
in human chondrocytes (Shakibaei et al., 2007), which indicates
that curcumin can inhibit the decomposition of cartilage matrix
and play a role in treating KOA. The experiment with human
chondrocytes as the research object shows that curcumin can
downregulate the expression of inflammatory factors in cells,
such as nitric oxide, prostaglandin 2, TNF-a, IL-6, and IL-8,
reduce cartilage inflammation, and then inhibit cartilage damage
(Crivelli et al., 2019; Kim and Kim, 2019). In this context,
combined with our NMA results, we believe that curcumin has
great clinical application value in the treatment of knee
osteoarthritis and may become a substitute for NSAIDs.
Therapeutic advantages of curcumin, a polyphenol,
against traumatic brain injury through interaction with
different inflammatory signaling pathways and their effects on
levels of cytokines and related biomarkers Molecular
Neurobiology | March 2024 The recent findings on curcumin
demonstrate its remarkable versatility as a molecule that
interacts with a variety of molecular targets. Various central
nervous system disease models have been shown to be susceptible
to curcumin's anti-inflammatory properties, including
intracerebral hemorrhage, global brain ischemia, and
neurodegeneration, all of which are associated with the
inflammation of the central nervous system. Similarly, curcumin
exerts neuroprotective effects in mammals when it crosses the
blood–brain barrier. Curcumin has been shown to reduce cerebral
edema, enhance membrane and energy homeostasis, and influence
synaptic plasticity following traumatic brain injury in studies.
Curcumin has been shown by numerous studies to be effective in
reducing inflammation. Research has shown that curcumin
suppresses the activation of NF-κB by inhibiting the
phosphorylation and degradation of IκB; as a result, curcumin
reduces the inflammation caused by NF-κB. The effects of
curcumin have been shown to be not only reduced post-traumatic
brain injury neuroinflammation, but also decreased levels of
inflammatory mediators that are produced following a traumatic
brain injury. The anti-inflammatory effects of curcumin were
demonstrated in an in vitro study using 100 mg/kg of curcumin.
According to the report, curcumin was able to reduce the amounts
of damage after traumatic brain injury induction and apoptosis,
particularly in the cortical cell model derived from embryonic
15-day pregnant mice, resulting in reduced damage. One study in
rats with traumatic brain injury administered 30 and 50 mg/kg of
curcumin daily for 35 days reduced levels of NLRP3, IL-1β, IL-6,
IL-18, and TNF-α. There was a reduction in neuroinflammation and
subsequent complications of TBI when curcumin was administered.
Furthermore, curcumin (at 500 mg/kg/day) decreased injury in the
ipsilateral cortex as a result of its ability to enhance
neutrophil infiltration (weight drop model-TBI). Curcumin
reduced apoptosis in cells and increased antioxidant activity,
suggesting potential neuroprotective effects. The pain levels
decreased when curcumin (50 mg/kg) was administered to
surgically induced traumatic brain injury rats. Curcumin has
been found to inhibit non-selective histone acetyltransferases,
suggesting potential benefits through histone acetylation. In a
rat model of TBI induced by FPI, curcumin (100 mg/kg) exerted
neuroprotective properties by activating the Nrf2 pathway. BDNF,
synapsin I, and CREB levels were reduced in animal models
following TBI after curcumin treatment (500 ppm). When given
oral doses of 100 mg/kg of curcumin per day, oxidative damage
was decreased, and omega-3 fatty acid DHA levels and 4-HNE (an
indicator of membrane lipid peroxidation) increased. Curcumin
supplements may have neuroprotective effects after brain injury
and may increase the activity of docosahexaenoic acid and fatty
acid-transport protein. According to Sharma et al.'s study
published in 2010, curcumin reduced iPLA2, 4-HNE, and STX-3,
which improved learning progress and relieved complications
associated with traumatic brain injury. Several studies, such as
the one by Zahedi et al., suggest promising effects of curcumin,
developing effective therapeutic strategies necessitates
rigorous preclinical studies and clinical trials.
Curcumin mitigates acrylamide-induced ovarian
antioxidant disruption and apoptosis in female Balb/c mice: A
comprehensive study on gene and protein expressions
Food Science & Nutrition | March 2024 Curcumin is known for
its antioxidant properties.Evidence has shown that curcumin
exhibits anti-inflammatory, antioxidants, anti-cancer activities
(Khajeh pour et al., 2023; Mailafiya et al., 2023). These
advantageous features are attributed to its elevated antioxidant
activity, stemming from the hydroxyl and methylene groups within
the β-diketone moiety present in its chemical structure (Chen et
al., 2023; Wang et al., 2017). There are several studies that
explored the positive effects of curcumin on the ovary tissue.
Azami et al. (2020) showed that curcumin could prevent ovarian
aging by increasing ovarian volume and the number of follicles.
Lv et al. (2021) also suggested that curcumin had beneficial
effects on the ovary and reproductive organs by regulating the
PTEN-AKT-FOXO3a pathway. Furthermore, ACR exposure led to a
significant increase in estradiol, luteinizing hormone,
testosterone, ovarian tumor markers such as CA125, and
carcinoembryonic antigen (CEA), while serum progesterone,
follicle-stimulating hormone, and total antioxidant capacity
decreased in female rats. Curcumin treatment restored
serological indices toward normal levels (Elsawi et al., 2023).
In our study, ACR exposure adversely affected ovarian
antioxidant defense thereby leading to increased pro-apoptotic
markers. Notably, curcumin treatment effectively mitigated these
effects, restored antioxidant potential, and reduced
acrylamide-induced toxicity in female mouse ovaries. Our
findings indicate that the administration of curcumin at doses
of 100 and 200 mg/kg efficiently restores the expression of
antioxidant genes, demonstrating a significant improvement at
the 200 mg/kg dose compared to the 100 mg/kg dose. Several
studies have illustrated the efficacy of curcumin in mitigating
oxidative stress-related concerns, encompassing factors like
total antioxidant capacity, malondialdehyde (MDA), and
superoxide dismutase (SOD) within physiological conditions (Chen
et al., 2022; Khayatan et al., 2023). In a recent systematic
review and meta-analysis of randomized controlled trials,
curcumin exhibited a substantial influence on indicators of
oxidative stress, including total antioxidant capacity,
malondialdehyde, and SOD levels (Dehzad et al., 2023). In
various animal models of ovarian diseases, curcumin has
demonstrated the ability to enhance overall ovarian function (Eser
et al., 2015; Wang et al., 2017). Furthermore, the
administration of curcumin has been proven beneficial in
addressing gynecological diseases in women, as highlighted in
studies (Kamal et al., 2021; Shen et al., 2022). For instance,
curcumin supplementation has beneficial effects on weight loss,
glucose and lipid metabolism, metabolic parameters, and androgen
levels in polycystic ovary syndrome patients (Ghanbarzadeh-Ghashti
et al., 2023; Sohaei et al., 2019). Curcumin causes a reduction
in serum nitric oxide release in women with primary dysmenorrhea
and premenstrual syndrome pain (Farrokhfall et al., 2023). It
also decreases the total score of primary symptoms of menopause
by affecting oxidative Stress Biomarkers (Farshbaf-Khalili et
al., 2022). Importantly, curcumin treatment emerged as a
promising therapeutic intervention, effectively restoring
antioxidant potential and mitigating acrylamide-induced toxicity
in the ovaries of female mice. These results contribute to a
deeper understanding of the molecular mechanisms involved in
ACR-induced reproductive toxicity and underscore the potential
of curcumin as a protective agent against such detrimental
effects.
Curcumin abrogates cobalt-induced neuroinflammation
by suppressing proinflammatory cytokines release, inhibiting
microgliosis and modulation of ERK/MAPK signaling pathway.
Journal of Chemical Neuroanatomy | March 2024 Curcumin
treatment significantly reduced tissue levels of proinflammatory
cytokines TNF-α and IL-1β. Microglial activation and ERK protein
upregulation induced by cobalt were attenuated by curcumin.
Results showed that curcumin abrogated neuroinflammation by
suppressing the release of proinflammatory biomarkers, reducing
microgliosis, and modulating the ERK MAPK pathway. Extensive
studies have suggested that curcumin possesses anti-inflammatory
(Wang et al., 2017), neuroprotective (Teter et al., 2019),
antioxidant (Memarzia et al., 2021), anti-cancer (Dou et al.,
2017), hepatoprotective (Macías-Pérez et al., 2019). Curcumin
significantly suppressed the release of neuroinflammation
markers and reduced microgliosis in the hippocampus of the rats.
In addition, the significant correlation between ERK expression
and proinflammatory biomarkers and microgliosis has offered some
mechanistic insight into curcumin's neuroprotective properties.
Curcumin in Cancer and Inflammation: An In-Depth Exploration of
Molecular Interactions, Therapeutic Potentials, and the Role in
Disease Management International Journal of
Molecular Sciences | March 2024 Curcumin, a polyphenolic
compound, is extracted from the turmeric plant. The significance
of curcumin’s structure, especially its conjugated enol-ketone
system, lies in its ability to engage in diverse molecular
interactions. In colorectal cancer, early studies indicated
potential benefits of curcumin in reducing polyp number and size
in familial adenomatous polyposis (FAP) patients, suggesting its
role in managing precancerous lesions. For head and neck cancer,
particularly oral leukoplakia, curcumin showed a significant
clinical response compared to placebo. It is also noteworthy
that the combination of clinical and histological responses
indicated a more pronounced effect of curcumin, suggesting its
potential utility in the early-stage management of oral
leukoplakia. In the context of multiple myeloma, particularly in
patients with monoclonal gammopathy of undetermined significance
(MGUS) or smoldering multiple myeloma (SMM), curcumin
demonstrated some promise. The promising results in certain
areas warrant continued research to optimize curcumin’s
formulation, delivery, and dosing to maximize its clinical
benefits.
Curcumin effects on glycemic indices, lipid profile,
blood pressure, inflammatory markers and anthropometric
measurements of non-alcoholic fatty liver disease patients: A
systematic review and meta-analysis of randomized clinical trial
Complementary Therapies in Medicine Volume | March 2024
Curcumin supplementation was associated with significant changes
in fasting blood glucose and homeostatic model assessment for
insulin resistance in adults with NAFLD. Curcumin
supplementation was associated with significant changes in
triglyceride, total cholesterol, and low density lipoprotein in
adults with NAFLD. Curcumin supplementation in doses of
50−3000 mg/day over 8–12 weeks was associated with significant
reductions in levels of FBG, HOMA-IR, TG, TC, LDL, weight and
BMI in patients with NAFLD. Previous studies have reported
curcumin as a safe complementary therapy for several diseases. A
systematic review suggested that curcumin is effective in
lowering low density lipoprotein, cholesterol (LDL-C), TG,
fasting blood glucose (FBG), homeostatic model assessment for
insulin resistance (HOMA-IR), and weight in NAFLD patients, and
it is well tolerated. Another study revealed that curcumin
supplementation has favorable effects on metabolic markers and
anthropometric parameters in patients with NAFLD. Also,
results of a randomized controlled trial suggest that curcumin
supplementation reduces serum lipids in patients with NAFLD.
A study showed curcumin supplementation has a favourable effect
on total cholesterol (TC), and BMI in participants with NAFLD.
Therefore, promoting curcumin as adjuvant treatment on NAFLD
patients might be justified. In conclusion, our study indicated
that curcumin supplementation in doses of 50 − 3000 mg/day over
8–12 weeks was associated with significant changes in FBG,
HOMA-IR, TG, TC, LDL, weight and BMI in adults with NAFLD.
Curcumin suppresses metastasis of triple-negative
breast cancer cells by modulating EMT signaling pathways: An
integrated study of bioinformatics analysis
Medicine | February 2024 Curcumin demonstrates potential
anticancer properties in the treatment of triple-negative breast
cancer cells. The findings suggest that the inhibitory effect of
curcumin on the motility of triple-negative breast cancer cells
could be attributed to the concurrent downregulation of specific
signaling pathways, through influencing the EMT signaling
process. This study employs a comprehensive approach that
integrates bioinformatics analysis with in vitro experimental
methodologies, providing substantial evidence supporting
curcumin’s potential in breast cancer therapy. Curcumin exhibits
its therapeutic potential in triple-negative breast cancer cells
by modulating multiple signaling pathways. These findings
provide experimental evidence for considering curcumin as a
potential therapeutic strategy in the treatment of
triple-negative breast cancer cells. This study concentrates on
curcumin, a yellow phenolic pigment derived from turmeric,
renowned for its anti-inflammatory, antioxidant, and
immunomodulatory properties. Recent research has shown that
curcumin is crucial in treating several tumors by modulating
typical cell biological effects such as cell proliferation,
apoptosis, cell cycle, and metastasis. Thus, curcumin may play a
significant role in the initiation and progression of various
cancers, including breast, lung, and liver cancers, through
affecting multiple signaling and molecular pathways, such as Rb,
P53, mitogen-activated protein kinase, phosphatidylinositol 3-K
(PI3K)/protein kinase B, and NF-kappaB (nuclear factor kappa B
cells, NF-κB). Previous studies have demonstrated curcumin’s
capacity to inhibit cell proliferation and invasion in human
triple-negative breast cancer cells. This study is significant
for its exploration of curcumin’s potential clinical
applications in treating triple-negative breast cancer cells. By
elucidating the antitumor mechanisms of curcumin in TNBC cells,
it establishes a crucial foundation for developing innovative
therapeutic strategies. Curcumin significantly inhibited the
proliferation of Hs578T and MDA-MB-231 cells. Flow cytometry
results showed that curcumin induced apoptosis in these cells
and arrested the cell cycle at the G2/M phase. Additionally,
Transwell assay results showed that curcumin effectively reduced
the motility of Hs578T and MDA-MB-231 cells. Enrichment analysis
of RNA sequencing data showed that the mechanism of action of
curcumin was significantly associated with signaling pathways
such as pathways in cancer, focal adhesion, and PI3K-Akt
signaling pathways. Finally, Western blotting analysis showed
that curcumin significantly decreased the expression levels of
key proteins including Fibronectin, mTOR, β-Catenin, p-Akt, Akt,
N-Cadherin, p-S6, and S6. Curcumin, an efficacious
anticancer compound isolated from turmeric rhizomes, mediates
its therapeutic effects through the modulation of various
cellular pathways. These include the suppression of tumor
metastasis, angiogenesis, and inflammation, alongside the
modulation of apoptosis, cell cycle progression, and resistance
to multiple drugs. The role of curcumin as a cancer
chemopreventive agent has been rigorously studied in various
cancer models. Recent studies have highlighted curcumin’s
antiproliferative and antimotility effects on breast cancer
cells. In this study, our objective is to elucidate the
antitumor properties of curcumin, focusing on its potential
mechanisms of action and therapeutic efficacy. Employing gene
enrichment analysis, incorporating both Gene Ontology and Kyoto
Encyclopedia of Genes and Genomes pathways, on RNA sequencing
data, we determined that curcumin predominantly acts through
pathways such as Pathways in cancer, Focal adhesion, PI3K-Akt
signaling pathway, and cell cycle. he CCK8 assay indicated that
curcumin markedly reduces the cellular activity of TNBC cells.
In parallel, Western Blot analysis revealed that curcumin lowers
the expression of key proteins, including N-Cadherin,
Fibronectin, β-Catenin, p-Akt, Akt, mTOR, p-S6, and S6, in
Hs578T and MDA-MB-231 cells. These proteins play crucial roles
in the EMT process and its related signaling pathways,
particularly the PI3K/Akt/mTOR pathway. The results imply that
curcumin’s inhibitory effect on the motility of triple-negative
breast cancer cells may stem from the simultaneous
downregulation of these signaling pathways, impacting the EMT
signaling cascade.
Curcumin Enhances the Anti-Cancer Efficacy of CDK4/6
Inhibitors in Prostate Cancer Archivos
Españoles de Urología | February 2024 This study aimed to
investigate the potential of combining cyclin-dependent kinase 4
and 6 (CDK4/6) inhibitors with curcumin, a natural compound
known for its anti-aging properties, to enhance the anti-cancer
efficacy in prostate cancer. Curcumin is a natural compound
extracted from turmeric, which has been shown to have multiple
biological activities, including anti-inflammatory, antioxidant
and anti-cancer effects. The synergistic effect observed in this
study suggested that curcumin may enhance the therapeutic
efficacy of CDK4/6 inhibitors in prostate cancer treatment,
further proving the previously reported findings. Furthermore,
this study revealed that curcumin regulated cellular aging
induced by CDK4/6 inhibitors through the inhibition of the mTOR
and STAT3 pathways, which was also reported in previous studies.
Similar conclusions were drawn in this study, which showed that
curcumin could modulate cellular senescence. Interestingly,
curcumin contributed to the anti-cancer effects of CDK4/6
inhibitors in prostate cancer treatment. Moreover, this study
revealed that curcumin could inhibit the stemness
characteristics of cancer cells induced by LY CM, as evidenced
by the downregulation of cancer stem cell markers ALDH1A1, CD44
and Nanog. The ability of curcumin to target cancer stem cells
provides further evidence of its potential as an effective
therapeutic agent in prostate cancer treatment. As previously
reported, the combination of curcumin and LY CM can inhibit the
dryness of cancer cells. Overall, the findings of this study
support the notion that combining CDK4/6 inhibitors with
curcumin may have clinical implications for the treatment of
prostate cancer. The findings of this study provide valuable
insights into the potential of combining CDK4/6 inhibitors with
curcumin in the treatment of prostate cancer.
The complex effect of polyphenols on the gut microbiota and
triggers of neurodegeneration in Parkinson’s disease
Zhurnal Nevrologii | February 2024 A promising
direction for influencing microflora and inflammatory changes in
the intestine is the use of polyphenols, primarily curcumin. The
review of experimental, laboratory, clinical research proving
the pleiotropic effect of curcumin, including its antioxidant,
anti-inflammatory, neuroprotective effects, realized both
through peripheral and central mechanisms is presented.
Immunomodulatory effects of curcumin on macrophage
polarization in rheumatoid arthritis
Frontiers in Pharmacology | February 2024 As a natural
compound, curcumin is favorable for improving symptoms in
rheumatoid arthritis patients due to its potent efficacy,
affordability, and minimal side effects. In addition, curcumin
has been reported to ameliorate several diseases via epigenetic
regulation, encompassing: (1) suppression of DNMTs; (2)
regulation of histone acetyltransferases and histone
deacetylases; and (3) regulation of miRNAs (Boyanapalli and
Kong, 2015). Several studies have shown that curcumin can be
used in cancer treatment to reverse DNA methylation, alter
histone modifications and target miRNA expression (Shu et al.,
2011; Bao et al., 2012; Yu et al., 2013). Curcumin has been
extensively demonstrated to possess anti-inflammatory,
antioxidant, immunomodulatory and anticancer properties in both
experimental and clinical studies (Xu et al., 2018). Curcumin
has shown strong therapeutic potential, especially in autoimmune
diseases, such as RA and systemic lupus erythematosus (SLE)
(Yang et al., 2019; Chamani et al., 2022; Kou et al., 2023). A
large number of investigations have indicated that curcumin
modulates macrophage polarization and function to alleviate
inflammation and therefore can be used to treat
inflammation-related diseases (Gao et al., 2015; Karuppagounder
et al., 2016; Abdollahi et al., 2023). Curcumin regulates the
functions of various immune cells, including macrophages
(Mohammadi et al., 2019), dendritic cells (DCs) (Rahimi et al.,
2021), B cells (Mohammadi et al., 2022) and T cells (Rahimi et
al., 2019), thereby modulating both innate and adaptive immunity
(Shehzad and Lee, 2013). The anti-inflammatory activity of
curcumin is due to its suppression of multiple signalling
molecules, including NF-κB, activated protein (AP)-1, MAPKs, and
protein kinase C (Kahkhaie et al., 2019). In addition, curcumin
is a potent inhibitor of reactive-oxygen-generating enzymes,
such as lipoxygenase, cyclooxygenase (COX), xanthine
dehydrogenase and iNOS (Rao, 2007). As shown in macrophages,
curcumin inhibits LPS and IFN-γ-induced nitric oxide production.
Curcumin mediated dendritic cell maturation by
modulating cancer associated fibroblasts
Journal of Cancer Research and Therapeutics | February 2024
Curcumin, traditionally known for its anti-inflammatory effects,
has been shown to be a potent immunomodulatory agent that can
modulate the activation of various immune cells by
downregulating pro-inflammatory cytokines, including IL-1, IL-2,
IL-6, IL-8, IL-12. In our previous studies, we have reported on
curcumin's different potential to target cancerous cells in
Acute myeloid leukemic (AML) patients as well as lung cancer
patients. Moreover, several reports have suggested that
curcumin-treated DCs produce significantly lower levels of IL-6,
IL-12, IL-10, and TNFα, thus creating a Th2 permissive
environment. In addition, there are several other reports
confirmed that curcumin inhibited IL-1b, IL-6 through modulation
of NF-kB and MAPK pathways. Moreover, curcumin-inhibited
IL-6-induced STAT3 phosphorylation and nuclear translocation in
multiple myeloma cells. Recently, Paul S and Sa G revealed that
curcumin acting as an adjuvant in immunotherapies may present
with novel approaches for researchers and clinicians to obtain
improved treatment outcomes. Collectively, our results concur
with previous findings reported by other researchers, signifying
curcumin’s potential to decrease the secretion of IL-6, IL-10,
and TGF-β in conditioned media, this being mediated via
curcumin’s efficacy to instruct cancer associated fibroblasts to
secrete exosomes resulting in the creation of an
immunomodulating TME from an immunosuppressive TME environment.
This study may provide basis to revise fundamental treatment
rationales and formulate synergistic therapeutic approaches by
using curcumin along with DC-based immunotherapies to overcome
cellular resistance in cancer treatment but it still requires
more in-depth research to have an in-sight into mechanism, which
might open up a newer avenues for curcumin’s use as an
appropriate immunotherapeutic modulator.
Exploring the therapeutic potential of curcumin in
oral squamous cell carcinoma Pathology -
Research and Practice | February 2024 Curcumin, a
polyphenolic compound derived from rhizomes of Curcuma longa
(turmeric), has garnered significant attention due to its
potential as an anticancer agent. Its pleiotropic properties,
including anti-inflammatory, antioxidant, and anti-tumor
activity, make it a compelling candidate for exploring novel
strategies in the oral cancer treatment. Of particular interest
is curcumin’s capacity to interfere with the intricate web of
cellular signaling pathways involved in angiogenesis and tumor
progression. Our study highlights the intriguing possibility of
curcumin being a multifaceted medicinal supplement in the fight
against oral cancer. Through its modulation of HIF-1α, VEFG,
STAT3, and MMP-3, curcumin shows promise in disrupting critical
pathways associated with angiogenesis and tumor progression,
offering new avenues for targeted cancer treatments. These
findings underscore curcumin’s significance in oral cancer
research and its potential for future clinical applications.
Curcumin
in Alzheimer’s Disease and Depression: Therapeutic Potential and
Mechanisms of Action Brazilian Archives of
Biology and Technology | February 2024 Curcumin is a
polyphenol present in Curcuma longa, a root used in Asian
cuisine for thousands of years, and it has several medicinal
properties, acting as an antioxidant, anti-inflammatory,
anticancer, among others. The aim of this study was to evaluate
the effects of curcumin in Alzheimer's disease and Depression,
which has as its main pathogenesis the reduction of BDNF levels,
monoamine levels, increased oxidative stress, inflammation,
beta-amyloid aggregation, Tau protein accumulation and aluminum
neurotoxicity, verifying its therapeutic capacity. Therefore, a
literature review was performed in the Scholar Google,
ScienceDirect, and PubMed databases. The data analyzed
demonstrated that curcumin supplementation is able to restore
BDNF levels in Alzheimer's disease and depression, in addition
to modulating monoamines and reducing oxidative stress,
inflammation, beta-amyloid aggregation, Tau protein accumulation
and aluminum neurotoxicity, improving their symptoms.
The Protective Effects of Curcumin against Renal Toxicity
Current Medicinal Chemistry | February 2024 Curcumin is a
naturally polyphenolic compound used for hepatoprotective,
thrombosuppressive, neuroprotective, cardioprotective,
antineoplastic, antiproliferative, hypoglycemic, and
antiarthritic effects. Kidney disease is a major public health
problem associated with severe clinical complications worldwide.
The protective effects of curcumin against nephrotoxicity have
been evaluated in several experimental models. In this review,
we discussed how curcumin exerts its protective effect against
renal toxicity and also illustrated the mechanisms of action
such as anti-inflammatory, antioxidant, regulating cell death,
and anti-fibrotic. This provides new perspectives and directions
for the clinical guidance and molecular mechanisms for the
treatment of renal diseases by curcumin.
Effect of Curcumin on the Process of
Neuroinflammation Caused by COVID-19
Curcumin and Neurodegenerative Diseases | February 2024
Curcumin, the main active ingredient of Curcuma longa L., has
antioxidant, anti-inflammatory, antitumor, antiviral,
neuroprotective, and immune system-modulating properties.
Because of these properties, this curcuminoid may be helpful
both before and after SARS-CoV-2 infections, enhancing health
status in the various complications brought on by the illness
(respiratory, enteric, hepatic, and neurological). From this
perspective, this chapter aims to report on findings regarding
the effect of turmeric on COVID-19-induced neuroinflammation.
Some studies highlight that curcumin is effective in COVID-19
conditions by inhibiting inflammatory and neuroinflammatory
signaling pathways, such as nuclear factor kappa B (NF-kB), and
the induction of various pro-inflammatory cytokines and
chemokines, including interleukin (IL)-6, interferon (IFN) γ,
monocyte chemoattractant protein (MCP)-1, tumor necrosis factor
(TNF)-α and IL-1β.
Effect of Curcumin on Dysmenorrhea and Symptoms of
Premenstrual Syndrome: A Systematic Review and Meta-Analysis
Korean Journal of Family Medicine | February 2024 The
reduction in the severity of PMS and dysmenorrhea has been
attributed to curcumin’s anti-inflammatory and antidepressant
activities. Studies have found that curcumin can alleviate
symptoms of dysmenorrhea and PMS. Evidence shows that curcumin
has pleiotropic effects and acts as an anti-inflammatory,
anticancer, antioxidant, and antibacterial agent. In addition,
curcumin can reduce prostaglandin production. Khayat et al.found
that curcumin can alleviate symptoms experienced before
menstruation without any adverse effects. Furthermore, curcumin
in women with PMS may also regulate neurotransmitters and
biomolecules, exert antioxidant and analgesic effects, and
reduce oxidative stress. In conclusion, the findings of our
meta-analysis showed that using various forms of curcumin could
reduce the severity of PMS and dysmenorrhea owing to its
anti-inflammatory and antidepressant activities. The present
study revealed that curcumin consumption immediately before or
during menstruation could alleviate the severity of
dysmenorrhea. Therefore, it could be regarded as an appropriate
alternative for women with PMS and dysmenorrhea to improve their
quality of life.
Review of the Protective Mechanism of Curcumin on
Cardiovascular Disease Drug Design,
Development and Therapy | February 2024 Curcumin has been
shown to have a variety of pharmacological properties over the
past decades. Curcumin can significantly protect cardiomyocyte
injury after ischemia and hypoxia, inhibit myocardial
hypertrophy and fibrosis, improve ventricular remodeling, reduce
drug-induced myocardial injury, improve diabetic
cardiomyopathy(DCM), alleviate vascular endothelial dysfunction,
inhibit foam cell formation, and reduce vascular smooth muscle
cells (VSMCs) proliferation. Clinical studies have shown that
curcumin has a protective effect on blood vessels. Toxicological
studies have shown that curcumin is safe. Curcumin is a
bioactive component of the curry spice, and its pleiotropic
effects in cardiovascular diseases suggest that it is a
promising drug candidate. Specifically, curcumin can
significantly alleviate vascular endothelial dysfunction,
inhibit foam cell formation, reduce VSMCs proliferation, protect
cardiomyocyte injury after ischemia and hypoxia, inhibit
myocardial hypertrophy and fibrosis, improve ventricular
remodeling, reduce drug-induced myocardial injury, and improve
DCM. The therapeutic effect and mechanism of curcumin have
become the focus of pharmacokinetic research. Curcumin has a
good therapeutic effect, especially in the cardiovascular field.
Previous reviews have summarized the protective effects of
curcumin on CVDs. In 2020, Li et al reviewed the preclinical
studies of curcumin in CVDs such as cardiac hypertrophy, heart
failure, abdominal aortic aneurysm, stroke, drug-induced
cardiotoxicity, and diabetic cardiovascular complications, and
reviewed the potential molecular targets of curcumin.
Pourbagher-Shahri et al also reviewed the effects of curcumin on
the cardiovascular system in 2021. The protective mechanism of
curcumin against cardiovascular diseases is complex and
networked. It is important to note that curcumin is a
complementary or alternative medicine, not a replacement for the
main treatment, and needs to be used under the guidance of a
doctor. To be sure, curcumin is an important drug that is worth
exploring.
Curcumin alleviates atrazine-induced cardiotoxicity
by inhibiting endoplasmic reticulum stress-mediated apoptosis in
mice through ATF6/Chop/Bcl-2 signaling pathway
Biomedicine & Pharmacotherapy | February 2024 Curcumin
displays promise in alleviating heart injury by alleviating
cardiac apoptosis. Curcumin, acclaimed for its pronounced
anti-inflammatory and antioxidant properties, has garnered
interest as a potential therapeutic agent. Collectively, our
findings illuminate curcumin’s cardioprotective effect against
ATR-induced injury, primarily through its anti-ERS and
anti-apoptotic activities, underscoring curcumin’s potential as
a therapeutic for ATR-induced cardiotoxicity. Curcumin has many
biological benefits, such as antioxidant, anti-inflammation and
immunoregulatory effect. Research has shown that curcumin can
help reduce damage to various systems in the body, such as the
cardiovascular, digestive, and respiratory systems. In addition,
adding the curcumin to the diet can significantly reduce the
body weight and body fat rate of mice which fed with high-energy
diet, and alleviate inflammation and diabetes in mice.
Meanwhile, curcumin significantly decreased the expression of
inflammatory factors induced by tumor necrosis factor-α in
adipocytes and the differentiation of preadipocytes. Mortezaee
and his colleague’s study shown that curcumin inhibits the
growth of tumor cells. Curcumin has various pharmacological
effects, including reducing inflammatory reactions and oxidative
stress, enhancing immunity, and combating infections. Recent
studies have shown that the cardioprotective benefits of
curcumin are facilitated through myriad mechanisms, among which
include the modification of gut microbiota makeup, inducement of
macrophage polarization, alleviation of oxidative stress, and
modulation of pivotal signaling pathways such as AMPK and mTOR.
In doing so, curcumin minimizes damage to the subcellular
structures within the myocardium. The present study revealed
that curcumin can alleviate the ATR-induced damage in cardiac
cells. This mitigation manifests as reductions in inflammatory
cell infiltration and subcellular membrane damage (including
mitochondria, endoplasmic reticulum, and nucleus) instigated by
ATR. Most notably, curcumin appears to have the capacity to
remediate myocardial damage.
Improving cognitive function with intermittent dose
escalation of curcumin extract in chemotherapy-induced cognitive
impairment patients: a randomized controlled trial
Advances in Traditional Medicine | February 2024 The group of
subjects receiving curcumin extract experienced clinically and
statistically significant improvements in cognitive function.
Administration of curcumin extract with intermittent dose
escalation regimen proved to be safe and able to improve
cognitive function of cognitive impairment patients clinically
and statistically significant. Recently, there has been multiple
pharmacological studies done to investigate the antioxidant,
antiinflamation, anticarcinogenic, and anti-bacterial effects of
curcumin. Curcumin is a safe natural product to be consumed by
humans (Abd El-Hack et al. 2021). Curcumin is also known to
increase the effectiveness of chemotherapeutic agents via
increasing cancer cells sensitization against chemotherapy and
protecting normal cells from chemotherapy damage (Tan and
Norhaizan 2019). Curcumin extract has several advantages,
including having a pleiotropic effect as anti-inflammatory,
antioxidant, and antiapoptotic (Panahi et al. 2021; Abd El-Hack
et al. 2021). Furthermore, curcumin extract also has
anti-carcinogenic effects. Thus, the combination of various
mechanisms of action makes curcumin extract a comprehensive
therapeutic modality to prevent or treat cellular damage,
especially due to exposure to neurotoxic and oxidative stress
chemotherapeutic agents (Liu et al. 2019; Akbari et al. 2020).
In addition, curcumin extract also has a low toxicity index, so
it has a broad and safe therapeutic window profile. Clinically,
curcumin extract has been widely tested and is known to have
neuroprotective effects. For example, curcumin extract can
inhibit cognitive function impairment caused by the oxidative
stress of cigarette smoke (Muthuraman et al. 2019). In the
context of chemotherapy, curcumin has been shown to improve
neurogenesis and synaptogenesis that play a role in brain
plasticity, as well as increase hippocampal autophagy so that it
can suppress the process of apoptosis in the central nervous
system, after exposure to cisplatin-based chemotherapy (Yi et
al. 2020). Thus, administration of curcumin extract in carcinoma
patients undergoing chemotherapy regimens can help prevent, even
improve, the symptoms of cognitive impairment. Based on the
results of the analysis of this study, valid evidence was found
that the administration of curcumin extract with the new regimen
was proven to be safe and effective in improving cognitive
function in patients with cognitive impairment due to
carboplatin-paclitaxel chemotherapy regimen.
Administration of curcumin extract with a dose escalation system
was proven to improve cognitive function of patients with
clinical and statistical significance. Administration of
curcumin extract with this dosage regimen has also been shown to
have a good safety profile.
A Review on Medicinal Benefits of Curcumin on Cancer
International Research Journal of Modernization in Engineering
Technology and Science | February 2024 Curcumin, a natural
polyphenol found in the food spice turmeric, has been shown to
inhibit the survival and proliferation of cancer cells and
trigger apoptosis without promoting side effects. In this
context, the regulation of the cell cycle and its modulation by
curcumin has attracted great attention in recent years. Curcumin
can inhibit cancer cells, cause apoptosis, inhibit angiogenesis,
inhibit the expression of anti-apoptotic proteins, as well as
inhibit the immune system of cancer cells. Various studies have
reported the antitumor activity of curcumin against breast
cancer, lung cancer, head and neck squamous cell carcinoma,
prostate cancer, and brain tumors. Curcumin and its derivatives
have attracted great attention in the last two decades due to
their biofunctional properties such as antibacterial, antifungal
and antiviral. Curcumin exerts its anti-cancer effect through
various mechanisms. Curcumin can inhibit the growth of many
cancer cells by reducing the regulation of anti-apoptotic cells,
activating caspases, and promoting tumor suppressors such as
P53. Curcumin has properties that scavenge free radicals and
therefore may play an important role in inhibiting the growth of
cancer. Many cellular and preclinical studies have shown that
curcumin can prevent DNA damage caused by oxidative factors
(such as ionizing radiation) by inhibiting free radicals and
reactive oxygen species. Curcumin prevents cancer formation by
inhibiting the formation of NF-kappaB. Curcumin prevents tumor
formation and growth by inhibiting and activating two enzymes
(Phase 1 and Phase 2). The motivation to use curcumin
stems not only from its therapeutic potential, but also from the
fact that curcumin is more easily absorbed by patients without
the side effects of many other medicinal products such as
nausea, vomiting, diarrhea, hair lossand more serious long-term
conditions such as liver failure. Various studies comparing
breast cancer incidence and cancer rates in India and the West
show that the risk of breast cancer is lower in India. Curcumin
can interact with various biochemical pathways of cancer cells
and survive by directly or indirectly binding to different
targets. Curcumin has been shown to interact with many targets,
including transcription factors, growth factors, DNA, RNA, and
many proteins involved in cell signaling pathways. The chemical
structure of curcumin has diverse properties that make it highly
effective and has many synergistic properties for various
molecular targets. Curcumin, the active ingredient of turmeric
extract, has been used for many years as anti-inflammatory,
antioxidant, anti-cancer and more. Although there is much to
learn about curcumin and its therapeutic properties, it has
great potential in the treatment and prevention of cancer.
Curcumin, a natural product, is not only non-toxic but also has
many effects on various pathways involved in tumorigenesis.
Curcumin Improves Chemotherapy Resistance in Breast
Cancer Cells via Inhibiting the Secretion of FGF2/FGFR2 from
Cancer-Associated Fibroblasts Journal of
Biological Regulators and Homeostatic Agents | February 2024
In this experiment, the data also showed that curcumin
effectively blocked breast cancer cell proliferation, induced
apoptosis, and boosted the breast cancer cell sensitivity to
PTX. Curcumin increases breast cancer cell sensitivity to PTX by
inhibiting the secretion of FGF2/FGFR2 from CAFs. Curcumin is a
polyphenol isolated from turmeric that belongs to the rhizome of
Zingiberaceae. In vivo and in vitro
investigations have demonstrated a variety of pharmacological
activities of curcumin. In addition to low toxicity, curcumin
has pharmacological actions, including anti-inflammation,
antioxidation, anti-hyperlipidemia, anti-atherosclerosis,
anti-tumor, anti-HIV virus, and other beneficial properties.
Many scholars have suggested that curcumin can be utilized to
treat malignant tumors and chronic diseases. In vitro
and in vivo experiments verified that curcumin has a
clear anti-tumor activity. It was reported that curcumin
inhibits the development of breast cancer through modulation of
multiple molecular targets, including p53, Wnt/β-catenin, and
PI3K/Akt/mTOR signaling pathways. Curcumin exhibits diverse
pharmacological properties, including anti-inflammation,
antioxidant, and anti-tumor. Curcumin exhibits diverse
pharmacological properties, including anti-inflammation,
antioxidant, and anti-tumor. Zou et al. focused on the
effect of curcumin on the breast cancer cell sensitivity to
cisplatin and discovered that curcumin enhanced the cisplatin
sensitivity. In addition, curcumin reversed the enhanced
resistance in breast cancer cells induced by CAFs-CM. We further
detected the roles of FGF2 and its receptor FGFR2 in the
chemo-sensitization of curcumin. Accordingly, curcumin may
increase the breast cancer cell sensitivity to PTX by inhibiting
the secretion of FGF2 and FGFR2 by CAFs. It provides a new idea
for combining curcumin with chemotherapy. This study revealed
the potential of curcumin in cancer therapy and provided a
foundation for combining curcumin with chemotherapy in the
treatment of breast cancer.
The Combination of Vitamin D and Curcumin Piperine Attenuates
Disease Activity and Pro-inflammatory Cytokines Levels
Insystemic Lupus Erythematosus Patients
Current Rheumatology Reviews | February 2024
Curcumin-piperine might synergise with vitamin D to induce
clinical remission in patients with systemic lupus
erythematosus. Curcumin supplementation in premenopausal women
and dysmenorrhea improves vitamin D levels. Several studies have
reported the efficacy of vitamin D or curcumin for SLE
treatment. Curcumin is a phenolic compound widely found in
ginger, turmeric, and curcuma plants and has the potential as an
immunomodulator for the complementary treatment of SLE. Curcumin
acts as an activator or inhibitor of several transcription
factors that play a role in activating and differentiating Th1,
Th2, Th17, and Tregs. In a previous report, curcumin
synergistically interacts with vitamin D because it is also a
natural ligand for the vitamin D receptor (VDR). Previous
studies reveal that administering a combination of curcumin and
vitamin D3 resulted in a better recovery of neuronal cells from
Alzheimer's disease. Another study demonstrates that curcumin
supplementation in premenopausal women and dysmenorrhea improves
vitamin D levels. Although vitamin D or curcumin-piperine alone
could improve the clinical outcome and cytokines levels in SLE,
curcumin-piperine combined with vitamin D had the best outcome
in improving the disease activity and cytokines levels among
patients.
Can curcumin supplementation break the vicious cycle
of inflammation, oxidative stress, and uremia in patients
undergoing peritoneal dialysis? Clinical
Nutrition ESPEN | February 2024 Curcumin supplementation for
twelve weeks attenuates lipid peroxidation and might reduce
uremic toxin in patients with chronic kidney disease undergoing
dialysis. Supplementation with 2.5 g of curcumin, three days a
week for 12 weeks, reduced the mRNA expression of nuclear factor
kappa B (NF-κB) and protein C- high-sensitivity reactive
(hs-CRP) in patients undergoing hemodialysis. In this
single-blind, randomised, controlled trial, we showed that a
12-week curcumin supplementation reduced the levels of MDA, a
standard marker of lipid peroxidation and showed a tendency to
reduce the pCS, a uremic toxin from gut microbiota, in patients
with chronic kidney disease undergoing dialysis. A review
based on twelve clinical trials comprising 631 patients with
chronic kidney disease showed that curcumin supplementation has
a favourable impact on oxidative stress, inflammation, and
proteinuria. Similarly, a recent study from our group showed
that curcumin supplementation for patients with chronic kidney
disease CKD undergoing hemodialysis significantly reduced NF-κB
mRNA expression and plasma levels of hs-CRP. Curcumin has
phenolic groups in its chemical structure, which has essential
antioxidant activity as it is a hydrogen donor, stabilising free
radical molecules directly. Indeed, curcumin has been tested
because of its antioxidant and anti-inflammatory effects in
patients with chronic kidney disease CKD. Our results showed
that curcumin supplementation may be a potential nutritional
strategy to help alleviate oxidative stress.
Effect of curcumin on malignant hepatocytes and
mitochondria studied using atomic force microscopy
Micron | February 2024 Curcumin, an active ingredient of
Curcuma longa, exerts anti-inflammatory, antioxidant and
anticancer effects on the liver (Reyes-Gordillo et al., 2017).
Most studies on the effects of curcumin on hepatoma cells have
focused on biological processes, including cell apoptosis, gene
expression, and the role of proteins (Darvesh et al., 2012).
Research has shown that curcumin induces cell apoptosis via the
mitochondrial pathway (Trujillo et al., 2014), while research on
curcumin in mitochondria has mainly focused on oxidation
reactions and protein expressions (Bai et al., 2022). The
chemical structure of curcumin is a lipophilicity polyphenol.
The viability of SMMC-7721 cells decreased with increasing
curcumin concentrations, and the change was statistically
significant when the curcumin concentration was higher.
A Review on the Extraction Process and Therapeutic
Activity of Curcumin on Diabetes Mellitus and Cancer
International Journal For Multidisciplinary Research | February
2024 Curcumin (diferuloylmethane), the active ingredient in
turmeric, has significant antioxidant, anti-inflammatory and
anti-cancer properties. Research (in vitro and in vivo) showed
that curcumin can also inhibits the activity of some signaling
molecules (such as transcription factors, various enzymes, such
as protein kinases) and can be modulated in this way
inflammatory process, gene expression and could possibly control
the effectiveness of curcumin for the treatment of many organ
diseases, mainly diabetes and its complications. Turmeric or
Curcuma Longa is a natural product whose medicinal
properties have been widely studied and a wide range of
therapeutic effects in various diseases, including
neurodegenerative, liver, kidney damage, cancer and diabetes
have been linked mainly to its curcuminoid content. Action of
curcumin or curcuminoids as a hypoglycemic agent or only as a
healing aid improve metabolic profile and improve
diabetes-related complications such as diabetes nephropathy and
cardiopathy are discussed. Curcumin has also been shown to be a
mediator of chemoresistance and radioresistance. Anticancer
effects have been observed in a number of clinical trials,
mainly a natural chemopreventive agent in colon and pancreatic
cancer, cervical neoplasia and Barrett's metaplasia. The potent
antiproliferative effects of curcumin, which interact with
multiple intracellular signaling pathways, may enhance the
antitumor effects of gemcitabine. Turmeric has also be widely
used as antioxidant, antiamyloid, antimicrobial, antitumor,
immune response modulating and neuroprotective effects. Curcumin
also had antidepressant properties by modulating the release of
serotonin and dopamine. Curcumin has been used as a dietary
supplement for centuries and is considered pharmacologically
safe. The multiple functions of curcumin that affect in a
chemopreventive and directly therapeutic way show that it could
be a potential anti-cancer drug. Curcumin promotes cell death in
a variety of animal and human cell lines, including leukemia,
melanoma, and breast, lung, colon, kidney, ovary, and liver
carcinomas. Curcumin promotes cell death in a variety of animal
and human cell lines, including leukemia, melanoma, and breast,
lung, colon, kidney, ovary, and liver carcinomas
The Use of Curcumin in the Treatment of Colorectal,
Breast, Lung, and Prostate Cancers: An In Vivo study Update
JLAR | January 2024 Studies have demonstrated
that curcumin can potentially treat various cancers. There is
evidence that curcumin has significant anti-cancer properties,
including tumor growth inhibition, metastasis inhibitory
activity, and angiogenesis. Several studies have demonstrated
the versatility and potential of curcumin in treating cancer.
Curcumin has considerable cancer treatment potential, based on
the in-vivostudies. Curcumin and its derivatives have had
bifunctional properties in the past two decades, such as
antioxidant and anti-inflammatory effects. The anti-cancer
properties of curcumin have been demonstrated in vitro
and in vivo at all stages of cancer growth, including
the disease's promotion and initiation. Curcumin treats a wide
range of diseases, including asthma, allergies, coughs,
bronchial hyperactivity, sinusitis, anorexia, coryza, and
hepatitis. Many studies show its anti-inflammatory, antioxidant,
anti-infectious, hepatoprotective, thrombosuppressive,
cardioprotective, chemopreventive, anti-arthritic, and
anticarcinogenic properties. Curcumin has also modulated several
molecular targets in the body. According to the combined
evidence presented in the included studies, curcumin is
potentially effective against various types of cancer,
highlighting its numerous anti-cancer properties. Researchers
have found that curcumin inhibits tumor growth, induces
apoptosis, suppresses angiogenesis, and modulates several
cellular signaling pathways against cancer. Considering its
broad spectrum of action, curcumin may be used as a
complementary treatment and an adjunct therapy for these common
types of cancer. As a result of this systematic review, curcumin
has the potential to be a promising anti-cancer agent against
colorectal, lung, prostate, and breast. It is clear that
curcumin has excellent potential as a cancer treatment agent,
and further study of its potential is warranted to achieve more
effective and holistic cancer treatments.
Protective role of curcumin in disease progression
from non-alcoholic fatty liver disease to hepatocellular
carcinoma: a meta-analysis Frontiers in
Pharmacology | January 2024 Curcumin demonstrates a
significant improvement in key indicators across the stages of
NAFLD, liver fibrosis, and HCC. The research results reveal that
curcumin effectively hinders disease progression at each stage
by suppressing inflammation. Curcumin exerted hepatoprotective
effects in the dose range from 100 to 400 mg/kg and treatment
duration from 4 to 10 weeks. With excellent anti-inflammatory,
antioxidant, and anti-cancer properties, curcumin is expected to
be an effective treatment for all stages of liver disease. Based
on the results of the quantitative analysis evaluated in this
system, we can conclude that curcumin is applicable to a
spectrum of NAFLD–LF–HCC models and that most liver diseases
proceed based on the hepatic inflammatory microenvironment. More
attention should be paid to the anti-inflammatory effects of
curcumin. Curcumin has been shown to be effective in
inhibiting the progression of NAFLD–LF–HCC at doses of 100–400
mg/kg over a 4–8 weeks duration with significant
hepatoprotective effects, and its therapeutic mechanisms are
related to multiple pathways, including anti-inflammatory,
antioxidant, and apoptotic regulations which are regulated in
all stages of liver disease.
The Effect of Curcumin on the Gut-Brain Axis:
Therapeutic Implications Journal of
Neurogastroenterology and Motility | January 2024 Several
types of nutrients, such as curcumin, have been proposed as
regulators of the dysbiotic state, and preclinical experiments
have suggested that curcumin is not only beneficial but also
safe. Curcumin possesses anti-inflammatory,
anti-atherosclerotic, neuroprotective and metabolic
disorder-modulatory effects. Indeed, the gut microbiota directly
interacts with curcumin to produce small catabolites that can be
absorbed through the intestinal wall, as confirmed by the high
concentration of curcumin in the gut after oral administration.
In addition, curcumin influences the gut microbiota by promoting
the growth of beneficial bacterial strains, improving microbial
richness and diversity as well as enhancing intestinal barrier
function. Curcumin also had beneficial effects on the gastric
tissue of diabetic gastroparesis model rats, exhibiting anti-gastroparetic
properties through improving ghrelin (a gut-brain peptide
hormone) expression, thereby balancing energy and promoting
gastrointestinal motility in the presence of oxidative stress.
Likewise, curcumin demonstrated a modulatory role on gastric
emptying via enhancing stem cell factor/c-kit signaling (through
reduction of oxidative stress) and the nuclear factor kappa B
cascade in the stomach of a diabetic gastroparesis rat model.
In fact, curcumin may be one of the non-invasive alternatives to
the invasive oral endoscopic gastric myotomy procedure. Curcumin
positively affects multiple pathways in Parkinson’s disease (PD)
treatment such as the inhibition of α-synuclein aggregation, an
increase in tyrosine hydroxylase, and reduction of N-acetylneuraminate
degradation, along with its influence on gut microbiota. Some in
vivo studies have indicated that the protective effect of
curcumin on neurodegenerative diseases and PD occurs through the
regulation of the gut microbiota by curcumin. Oral
administration of curcumin can alter the diversity of beneficial
or pathogenic bacteria accord- ing to the dose, duration of
treatment or formulation. In addition, curcumin and its
metabolites may have a direct impact on neurons, hormones,
blood, lymphatic vessels, and immune cells; thus, it is likely
that the direct and indirect effects of curcumin (gut-brain
axis) act together synergistically to modulate disease and
improve host health. Based on the beneficial effects of curcumin
on health-promotion, disease management, and its wide
application as a spice in daily food, this review has sought to
understand the interplay between curcumin and the gut-brain axis
in multiple diseases, mainly based on available in vivo
experimental models. The findings presented here indicate that
curcumin has promising potential, with acceptable efficacy, as a
regulator of the gut-brain axis in several dis- eases associated
with GM dysbiosis. In addition, curcumin can not only act as a
treatment but is also able to interact with intestinal
microflora in dysbiosis to target microbiota activation or
suppression, thereby enhancing its therapeutic effect through
the production of more active metabolites and better
pharmacokinetics.
Curcumin
Mitigates the High-Fat High-Sugar Diet-Induced Impairment of
Spatial Memory, Hepatic Metabolism, and the Alteration of the
Gut Microbiome in Alzheimer’s Disease-Induced (3xTg-AD) Mice
Nutrients | January 2024 Curcumin
enriched beneficial gut microbiota. The observed alteration in
these gut microbiota profiles suggests a potential crosswalk in
the liver and brain for regulating metabolic and cognitive
functions, particularly in the context of obesity-associated
cognitive disfunction, notably Alzheimer’s disease. Curcumin, a
major bioactive chemical constituent derived from turmeric, has
been found to exhibit a range of neuroprotective effects,
including the reduction in the amyloid burden,
neuroinflammation, oxidative stress, infection, and
inflammation. Previous findings also provided evidence of the
modulatory role of curcumin in mediating several targets of
metabolic diseases. Reduced plasma glucose and triglyceride and
improved β cell function and afamin levels were also evident
after curcumin consumption in some clinical trials. Our previous
studies have demonstrated the protective effects of curcumin on
metabolic dysfunctions such as body weight gain, liver fat
accumulation, and dysregulated insulin homeostasis in HFHSD-fed
middle-aged and old mice. Curcumin supplementation demonstrated
a notable impact on body weight gain in the 3xTg-AD mice
subjected to HFHSD. This aligned with the previous findings from
our studies and others, revealing a consistent reduction in body
weight in the mice following curcumin supplementation,
particularly under various metabolic challenges. Curcumin
supplementation effectively ameliorated these memory deficits,
as evidenced by an enhanced performance during the Y-maze test,
consistent with our prior finding. In conclusion, our study
demonstrated the multifaceted effects of curcumin on the body
weight, metabolic pathways, memory function, and gut microbiota
in 3xTg-AD mice under HFHSD conditions. The selective reduction
in body weight gain, improvements in memory function, and the
modulation of the metabolic pathways suggest the potential
therapeutic value of curcumin in mitigating Alzheimer’s-related
symptoms.
Curcumin Inhibits Bladder Cancer by Inhibiting
Invasion via AKT/MMP14 Pathway Discovery
Medicine | January 2024 Curcumin could inhibit bladder cancer
by inhibiting invasion through the AKT/MMP14 pathway. The target
of curcumin for bladder cancer includes signal transducer and
activator of transcription 3 (STAT3), AKT, cyclin A2 (CCNA2),
epidermal growth factor receptor (EGFR), E1A binding protein
p300 (EP300) and MMP14. MMP14 was highly expressed in bladder
cancer than in normal tissues and was associated with a worse
prognosis (p < 0.05). Curcumin could inhibit the proliferation
and migration of bladder cancer cells.
Targeting endothelial cells with golden spice
curcumin: A promising therapy for cardiometabolic multimorbidity
Pharmacological Research | January 2024 Curcumin, a widely
used dietary supplement derived from the golden spice
Curcuma longa, has demonstrated remarkable potential in
treatment of CMM through its interaction with endothelial cells.
Numerous studies have identified various molecular targets of
curcumin (such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1β, HO-1, NOs,
VEGF, ICAM-1 and ROS). These findings highlight the efficacy of
curcumin as a therapeutic agent against cardiometabolic
multimorbidity through the regulation of endothelial function.
Curcumin, derived from the golden spice Carcuma longa and widely
used as a dietary supplement, possesses anti-inflammatory,
analgesic, anti-angiogenic and anti-oxidative properties.
Several studies have demonstrated that the therapeutic effects
of curcumin against cardiometabolic multimorbidity were
attributed to its ability to target ECs. Studies have shown that
in patients with obesity, curcumin (oral, 1 g/d for 4 weeks)
could effectively regulate inflammation and immunity by reducing
levels of hs-CRP, IL-1β, IL-4, or VEGF, and decreased levels of
MCP-1, IL-6, and TNF-α in serum of metabolic syndrome (MS)
patients. Curcumin, a natural compound derived primarily from,
the rhizomes of Curcuma longa, possesses significant
pharmacological properties. Extensive studies have confirmed its
high oral safety. Additionally, our review has highlighted the
tremendous potential of curcumin in the treatments a majority of
cardiometabolic multimorbidities by the alleviation of
endothelial damages. Furthermore, research studies have
demonstrated the potential of curcumin in alleviating
endothelial inflammation, oxidative stress, and cellular
inflammation caused by diverse pathological conditions, such as
hyperglycemia, hyperlipidemia, hypertension, atherosclerosis,
cerebral ischemia, and myocardial infarction. In animal models
of obesity, MS, diabetes, and related complications, curcumin
was administered at a higher dose and for a longer duration of
300–400 mg/kg/day for 8–12 weeks. This dosage exceeds the amount
used to treat hypertension, atherosclerosis, and cerebral
ischemia, which falls within a dosing range of 100–200 mg/kg/day
for 4–6 weeks.
Examination
of the effect of curcumin supplementation on liver enzymes and
some physiological parameters in volleyball players
Revista de Gestão e Secretariado | January 2024
It has been observed that curcumin supplementation applied in
addition to volleyball training affects the lipid metabolism and
physiological parameters of the athletes. In line with this
information, we believe that the supplements to be applied in
addition to their routine training will positively affect the
athletic performance of the athletes. Curcumin has been
investigated for its anti-obesity, anti-inflammation,
anti-cancer, anti-angiogenesis, anti-diabetes, hepatoprotection,
radioprotection, and chemopreventive action. Curcumin is also
said to affect obesity and lipid metabolism via a number of
pathways, including energy metabolism regulation, inflammation
suppression, and angiogenesis. Turmeric has lately gained
widespread interest from researchers who have done studies
demonstrating that its therapeutic characteristics are linked to
pain relief, as well as the prevention and treatment of
cardiovascular, cancer, and other chronic diseases. Curcumin
administration has also been shown to improve physical activity
and sports performance in animal studies. Curcumin
supplementation is said to aid in muscle repair and
inflammation reduction, improve mitochondrial biogenesis, reduce
oxidative stress, and prevent fatigue and muscle damage. During
aerobic exercise (1 hour treadmill jog), there was a substantial
reduction in physical exercise-derived inflammation compared to
the pre-exercise moment in studies when turmeric supplementation
was used. Despite some inconsistent results, curcumin
administration appears to be useful for pain relief as well as
muscle damage mitigation by lowering serum CK. Nicol et al.
(2015) found that those treated with curcumin (5 g/day -5 days)
had less muscular pain and lower CK serum values (22-9%; ±
21-22%) at 24-and 48 hours. Curcumin supplementation for 8 weeks
resulted in substantial improvements in CRP, LDH, MDA, and VO2
max values in healthy young adult women in trials. It has been
observed that curcumin supplementation applied in addition to
volleyball training affects the lipid metabolism and
physiological parameters of the athletes. In line with this
information, the diversity of nutrients or compounds derived
from food factors or medicinal plants can be explored to
understand their possible effects on exercise physiology and the
different bioactivities that can be used for health promotion.
Profiling Inflammatory Biomarkers following Curcumin
Supplementation: An Umbrella Meta-Analysis of Randomized
Clinical Trials Evidence-Based
Complementary and Alternative Medicine | January 2024 The
umbrella of meta-analysis suggests curcumin as a promising agent
in reducing inflammation as an adjunctive therapeutic approach
in diseases whose pathogenesis is related to a higher level of
inflammatory biomarkers. Curcumin is remarkable bioactive
polyphenol extracted from the rhizome of turmeric (Curcuma
longa). Curcumin has a wide range of medicinal effects such
as hepatoprotective, antimicrobial, anti-inflammatory,
antioxidant, and antitumor activities. The anti-inflammatory
feature of curcumin is mediated by several pathways. Intestinal
alkaline phosphatase, an endogenous antioxidant and
anti-inflammatory enzyme, is upregulated by curcumin. Moreover,
curcumin modulates inflammatory markers through nuclear
factor-erythroid factor 2-related factor 2 (NRF2∗)-Keap1
regulatory pathway. Given these effects, curcumin can have
regulatory effects on the level of inflammatory biomarkers such
as CRP, IL-6, and TNF-α. According to the US Food and Drug
Administration (FDA) report, curcumin has been considered as
“Generally Recognized as Safe” (GRAS) even at doses between 4000
and 8000 mg/day. The beneficial effect of curcumin on various
health conditions in some studies shows that the
anti-inflammatory effect of curcumin is not dependent on the
disease. Curcumin has a polyphenol nature; therefore, its
anti-inflammatory mechanisms may be due to its antioxidant
properties. Many properties of curcumin such as antioxidant,
anti-inflammatory, antimicrobial, and antimutagenic attribute to
the presence of hydroxyl and methoxy groups in the curcumin
structure. The present study shows that curcumin has reducing
effects on IL-6, CRP, and TNF-α levels. Therefore, curcumin can
be considered as a useful agent for longevity through decreasing
oxidative stress.
Anti-Inflammatory
Mechanisms of Curcumin and Its Metabolites in White Adipose
Tissue and Cultured Adipocytes Nutrients |
January 2024 Overall, our in vivo and in vitro studies
demonstrate that curcumin alleviated diet-induced
obesity-associated inflammation. The plant-derived polyphenol
curcumin alleviates the inflammatory and metabolic effects of
obesity, in part, by reducing adipose tissue inflammation. Both
curcumin and its metabolites reduced LPS-induced adipocyte IL-6
secretion and mRNA levels. Proteomic analyses indicated that
curcumin upregulated EIF2 and mTOR signaling pathways. Overall,
curcumin exerted anti-inflammatory effects in adipocytes.
Previously, we reported that curcumin exerted protective
metabolic effects in diet-induced obese mice, independent of
changes in body weight. Curcumin’s effects may have been
mediated through its metabolic products, which are produced in
the gut, liver, or other tissues.
The
Effects of Curcumin on Neurodegenerative Diseases: a Systematic
Review Journal of Herbal Medicine | January
2024 Curcumin has been considered in the therapeutic approach
to neurodegenerative diseases due to its relevant antioxidant
and anti-inflammatory properties. Adding curcumin to traditional
drug therapy appears promising and safe for treating
neurodegenerative diseases. Curcumin could be an option due to
its antioxidant, anti-inflammatory, and immunomodulatory
properties (Colaço et al., 2023, Grant et al., 2023, Marton et
al., 2022). The consumption of this plant or its derivatives,
such as curcumin, can improve the function and structure of
synapses by regulating proteins and delaying neuronal
dysfunction processes.
Antioxidant curcumin induces oxidative stress to
kill tumor cells (Review) Oncology Letters
| January 2024 Curcumin is a plant polyphenol in turmeric
root and a potent antioxidant. Curcumin is a plant polyphenol in
the rhizome of turmeric and was classified as a third-generation
cancer chemopreventive agent by the National Cancer Institute.
Several studies have reported anticancer mechanisms mediated by
curcumin through the induction of elevated ROS. Curcumin has
anti-inflammatory, antibacterial, hepatoprotective and
anticancer properties, and its anticancer effects have been
reported in several tumor types. In melanoma, curcumin has been
reported to increase the ROS level and activate oxidative stress
in the cysteine asparaginase pathway, which causes tumor cell
death. Furthermore, curcumin-induced accumulation of ROS in
tumors to kill tumor cells has been noted in several studies, as
discussed in the present review. Curcumin is well tolerated by
humans. For example, a study that evaluated the toxicity of
curcumin in humans reported that subjects administered 8 mg/day
curcumin did not develop toxicity. Curcumin is a natural
compound that has been used for the treatment of numerous types
of diseases, such as Alzheimer's disease, fatty liver and
cancer. Of note, curcumin has a dual role in oncological and
non-oncologic diseases. Specifically, in non-neoplastic
diseases, curcumin is a potent antioxidant that attenuates
oxidative stress and mitochondrial damage. Conversely, in
tumors, curcumin binds to several enzymes and increases ROS
levels. These different effects may be the result of differences
in dosage. For instance, in a previous study on curcumin
treatment of drug-resistant tumor cells, a low dose of curcumin
showed no effect on antioxidant proteins, whereas a high dose
resulted in the inhibition of antioxidant proteins, thereby
increasing ROS levels. Furthermore, mitochondria may be a
potential target for high-dose curcumin. In addition, compared
with normal cells, proteins abnormally expressed in tumor cells,
such as GSH and HO-1, may be targeted by curcumin to cause
oxidative stress in tumor cells. In terms of autophagy,
curcumin has been reported to induce elevated ROS levels and the
appearance of autophagy markers and autophagosomes, causing
tumor cells to undergo autophagy. Curcumin achieves anticancer
effects by regulating the expression of Nrf2 and its downstream
target HO-1, inhibiting the expression of GPX4 and altering the
accumulation of intracellular iron and inducing the Fenton
reaction. Over the past two decades, the mechanisms by which
curcumin inhibits several types of tumor have been gradually
elucidated. In conclusion, curcumin may have the potential
to become a cutting-edge drug for the treatment of tumors and
other diseases.
Antioxidant, anti-inflammatory and epigenetic
potential of curcumin in Alzheimer's disease
BioFactors | January 2024 Curcumin - an integral component of
traditional medicine in numerous cultures worldwide - has
garnered interest as a promising Alzheimer's disease treatment.
Current research indicates that curcumin may exhibit therapeutic
potential in neurodegenerative pathologies, attributed to its
potent anti-inflammatory and antioxidant properties.
Additionally, curcumin and its derivatives have demonstrated an
ability to modulate cellular pathways via epigenetic mechanisms.
This article aims to raise awareness of the neuroprotective
properties of curcuminoids that could provide therapeutic
benefits in Alzheimer's disease. The paper provides a
comprehensive overview of the neuroprotective efficacy of
curcumin against signaling pathways that could be involved in
Alzheimer's disease and summarizes recent evidence of the
biological efficiency of curcumin in vivo. Curcumin is a
naturally occurring polyphenol found in turmeric, which has long
been utilized in traditional medicine for its anti-inflammatory
and antioxidant properties. Curcumin's anti-inflammatory
properties stem from its capability to inhibit multiple
proinflammatory signaling pathways mediated by nuclear factor
kappa B (NF-kB) and immune cell activation. Through this
modulation of inflammatory mediators, encompassing cytokines,
adhesion molecules, growth factors, and enzymes, curcumin holds
the potential for therapeutic benefits. Numerous studies have
investigated the therapeutic potential of curcumin against
various neurodegenerative diseases, including Alzheimer's
disease. Some evidence suggests that curcumin may be able to
counteract the formation of amyloid plaques. Additionally,
curcumin has been found to modulate Alzheimer's
disease-associated epigenetic changes by influencing methylation
patterns, microRNAs, and histone-modifying enzymes. Multiple
human studies suggest a potential of curcumin to modulate
Alzheimer's disease pathways in-vivo. Zhang et al.'s 2006
findings demonstrated in-vivo effectiveness of curcumin in
clearing amyloid deposits. It was observed that treatment of
macrophages of Alzheimer's disease patients with curcuminoids
notably enhanced the uptake of Aβ. Research by DiSilvestro et
al. extended these findings, investigating the effect of
curcumin on inflammatory pathways and Aβ clearance in healthy
middle-aged individuals. Daily administration of a low dose of
curcumin has exhibited potential in reducing plasma levels of Aβ
protein and augmenting antioxidant capacity by elevating the
levels of radical scavenging enzymes catalase and
myeloperoxidase. In a different study, a solid lipid formulation
of curcumin was observed to enhance cognitive performance,
alleviate fatigue, and mitigate the detrimental effects of
psychological stress. Further exploration into the therapeutic
potential of curcumin in Alzheimer's disease was initiated by
Baum et al.'s double-blind study in 2008. Their 6-month clinical
study confirmed the previously described advantageous effects of
curcumin in Alzheimer's disease, as such showing its potential
to promote disaggregation of Aβ and anti-inflammatory and
antioxidant responses. In 2020, Thota et al. demonstrated that
daily oral curcumin supplementation for 12 weeks could decrease
circulating levels of islet amyloid peptide (IAPP) and glycogen
synthase kinase-3 (GSK-3β), both implicated in insulin
resistance. Curcumin and its metabolites have been shown to play
a neuroprotective role, with the capacity to alter the
pathological sequelae that may lead to Alzheimer's disease.
Curcumin's demonstrated antioxidant and anti-inflammatory role,
along with its high safety profile, poses an intriguing
possibility in preventing and treating Alzheimer's disease.
Curcumin
in Alzheimer’s Disease and Depression: Therapeutic Potential and
Mechanisms of Action Brazilian Archives of
Biology and Technology | January 2024 Curcumin is a
polyphenol present in Curcuma longa, a root used in Asian
cuisine for thousands of years, and it has several medicinal
properties, acting as an antioxidant, anti-inflammatory,
anticancer, among others. The data analyzed demonstrated that
curcumin supplementation is able to restore BDNF (Brain Derived
Neurotrophic Factor) levels in Alzheimer's disease and
depression, in addition to modulating monoamines and reducing
oxidative stress, inflammation, beta-amyloid aggregation, Tau
protein accumulation and aluminum neurotoxicity, improving their
symptoms. Curcumin has several medicinal properties as
antioxidant, anti-inflammatory, anti-HIV, antibacterial and
antitumor effect. In addition, curcumin is also used as a
therapeutic agent in inflammatory bowel disease, pancreatitis,
arthritis, some types of cancer [24], head trauma, anxiety,
Parkinson’s, depression, Alzheimer's disease, as well as acting
as BDNF restorer. Most of curcumin benefits can be attributed to
its anti-inflammatory action, obtained by the modulation of the
expression and production of enzymes such as cyclooxygenase-2
(COX-2), lipoxygenase and inducible nitric oxide synthase
(iNOS), and by the inhibition of inflammatory cytokines,
including interleukin and tumor necrosis factor alpha (TNF-α),
monocyte chemotactic protein (MCP), among others. In
neurodegenerative and neuropsychological diseases, curcumin's
role in restoring BDNF levels and, consequently, promoting
neurogenesis, is extremely important and may contribute to the
reversal of cognitive and mood disorders. After chronic curcumin
supplementation, subjects had a significant reduction in
depressive symptoms, with a reduction in the Hamilton Depression
scale and the Montgomery-Asberg scale. Curcumin supplementation
was also able to elevate plasma BDNF levels and reduce
inflammatory cytokines TNF-α and IL-1β, and salivary cortisol
concentrations, when compared to the placebo group. These
results suggest that supplementation with curcumin is able to
improve the action of selective serotonin reuptake inhibitor
class of antidepressants, such as escitalopram, mainly by
increasing BDNF levels, inhibiting proinflammatory cytokines and
reducing cortisol secretion. Therefore, there is strong evidence
of curcumin potential as a therapeutic agent in the
neuropsychological and neurodegenerative context, especially
when used in more bioavailable and high-quality formulations. In
summary, the data presented suggests that curcumin is able to
prevent and improve the symptoms of Alzheimer’s disease through
the improvement of cognitive and memory deficit by restoring
BDNF levels, reducing oxidative stress, inflammation,
beta-amyloid aggregation, Tau protein accumulation and aluminum
neurotoxicity. In Depression, curcumin treatment was also able
to improve its symptoms by restoring BDNF levels, modulating
monoamines and reducing inflammation. This study helps to
clarify the various mechanisms of action of curcumin in the
neurodegenerative / neuropsychological diseases, Alzheimer’s
disease and depression, suggesting it as a potential therapeutic
agent without any significant side effects.
Targeted therapies of curcumin focus on its
therapeutic benefits in cancers and human health: Molecular
signaling pathway-based approaches and future perspectives
Biomedicine & Pharmacotherapy | January 2024 Curcumin
modulates several biochemical pathways and targets involved in
cancer growth. Owing to its anti-inflammatory, antioxidant,
mutagenic, and antibacterial properties, curcumin has been
utilized as medication in Asian countries owing to their
antioxidant and anticancer activities. Additionally, it
has been shown to be advantageous for kidneys. Curcumin has
several medical uses, most of which are attributed to its
inflammatory and antioxidant properties. Curcumin has
anticancer, anti-inflammatory, antioxidant, and neuroprotective
properties, potentially managing diabetes, easing arthritis, and
potentially reducing inflammation in bowel diseases. Curcumin
can cure metabolic syndrome, anxiety, hyperlipidemia, and
oxidative and inflammatory diseases. Furthermore, a low dose can
still be beneficial for one's health, even if they have not been
diagnosed with a health condition. It has great potential as a
cancer treatment.
Curcumin
and breast cancer: therapeutic potential and mechanism in
multi-drug resistance Cancer Genomics |
January 2024 The sensitizing effects of curcumin have been
studied in composition with chemotherapy drugs including
cisplatin,paclitaxel, doxorubicin, and 5-fluorouracil in BC
celllines such as MCF-7, MCF-7ADR, MDA-MB-231. Studies reported
that curcumin increases the sensitivity in the resistant cells
to chemotherapy drugs, which has apoptotic and growth inhibitory
effects. Also, curcumin could decrease multi-drug resistance
breast cancer through induction ofautophagy by down-regulate the
expression of CCAT1, PI3K/Akt/mTOR pathway. According to
the results of preclinical studies, curcumin administration can
inhibit the multi-drug resistance in breast cancer cells.
Analysis: Aaron Rodgers' remarkable recovery sets
standard for players who tear an Achilles tendon
The Independent | January 2024 Aaron Rodgers defied
conventional medicine by returning to practice just 77 days
after surgery for a torn Achilles tendon. Rodgers had a “speed
bridge” procedure that’s designed to expedite the recovery
process. He said Thursday that he attributes his progress to
working hard in rehab and a strict diet: “High levels of
curcumin, high levels of collagen and drinking freakin’ bone
broth every single day.” The soon-to-be 40-year-old Rodgers may
have cracked the code for an injury that’s typically
season-ending and normally takes players at least nine months to
recover. No professional athlete is known to have returned from
it in less than five months.
Curcumin
for Treating Breast Cancer: A Review
Pharmaceutics | January 2024 Curcumin, a phytochemical
derived from Curcuma longa (turmeric), has shown
substantial potential in inhibiting BC cell migration,
metastasis, and proliferation. Curcumin constitutes the primary
bioactive compound found in the plant Curcuma longa,
commonly known as turmeric. Curcumin, a natural compound found
in the turmeric plant Curcuma longa, is generally
considered safe when consumed in amounts commonly found in foods
and traditional herbal remedies. In 2021, the European Food
Safety Authority (EFSA) established an acceptable daily intake
of curcumin at 3 mg/kg body weight. For optimal pharmacological
effects, an oral dose of more than 8.0 g/day is often required.
Numerous clinical studies demonstrated that a daily intake of 12
g of curcumin is well tolerated and safe. Curcumin
unquestionably exhibits potential as an anticancer agent, with
relevance not only to breast cancer but also to lung cancer,
gastric cancer, and other malignancies.
Protective
role of curcumin in disease progression from non-alcoholic fatty
liver disease to hepatocellular carcinoma: a meta-analysis
Frontiers in Pharmacology | January 2024 Curcumin
demonstrates a significant improvement in key indicators across
the stages of NAFLD (Non-Alcoholic Fatty Liver Disease), liver
fibrosis, and HCC (Hepatocellular Carcinoma). The research
results reveal that curcumin effectively hinders disease
progression at each stage by suppressing inflammation. With
excellent anti-inflammatory, antioxidant, and anti-cancer
properties, curcumin is expected to be an effective treatment
for all stages of liver disease. This is the first meta-analysis
to correlate Non-Alcoholic Fatty Liver Disease, liver fibrosis,
and hepatocellular carcinoma and evaluate the therapeutic
effects of curcumin on systemic liver disease. The mechanisms of
curcumin in the inhibition of the transition from Non-Alcoholic
Fatty Liver Diseaseto HCC are multiple, well-established, and
multi-targeted. The phenotypes involved are mainly related to
oxidative stress, inflammation, and apoptosis. Based on the
results of the quantitative analysis evaluated in this system,
we can conclude that curcumin is applicable to a spectrum of
Non-Alcoholic Fatty Liver Disease–LF–HCC models and that most
liver diseases proceed based on the hepatic inflammatory
microenvironment. In the development of a range of liver
diseases, one of the most remarkable molecular changes driving
the Non-Alcoholic Fatty Liver Disease–LF–HCC axis is the NF-κB
signaling pathway, so anti-inflammatory processes play a crucial
role in all three disease stages. More attention should be paid
to the anti-inflammatory effects of curcumin. Curcumin
exerted hepatoprotective effects in the dose range from 100 to
400 mg/Kg and treatment duration from 4 to 10 weeks. The
mechanistic analysis reveals that curcumin primarily exerts its
hepatoprotective effects by modulating multiple signaling
pathways, including TLR4/NF-κB, Keap1/Nrf2, Bax/Bcl-2/Caspase 3,
and TGF-β/Smad3. In summary, curcumin has shown promising
therapeutic effects during the overall progression of
Non-Alcoholic Fatty Liver Disease-LF-HCC. It inhibited the pathological progression by
synergistic mechanisms related to multiple pathways including
anti-inflammatory, antioxidant, and apoptosis regulation.
Therapeutic effects of curcumin on
constipation-predominant irritable bowel syndrome is associated
with modulating gut microbiota and neurotransmitter
Frontiers in Microbiology | January 2024 In a
30-day randomized trial, in subjects with irritable bowel
syndrome, abdominal bloating can be successfully reduced with a
supplementation with curcumin (Giacosa et al., 2022). Previous
studies have shown that CUR has a significant effect on reducing
the levels of 5-HT in serum and colon (Yu et al., 2019).
Curcumin is the major active constituent of Curcuma
longa. Modern studies have demonstrated its potent
anti-inflammatory (Kocaadam and Şanlier, 2017), antioxidant (Ahangarpour
et al., 2019), and antidepressant (Chang et al., 2016) effects.
It has been found that treatment with curcumin can modulate 5-HT
levels, with treatment with curcumin significantly increasing
5-HT levels in the hippocampus, while decreasing 5-HT levels in
the colon in IBS models (Yu et al., 2015). Curcumin can interact
directly with the gut microbiota. Curcumin has been shown to
positively affect the gut microbiota and modulate microbiota
composition and function, further improving gut health (Ng et
al., 2018). These studies support the potential therapeutic
effect of curcumin on IBS-C through modulation of the gut
microbiota and neurotransmitters. The results of this study show
that curcumin is able to decrease the levels of HT, VIP and SP
and regulate the gut microbiota in rats with irritable bowel
syndrome-C, and then exert the therapeutic effect on irritable
bowel syndrome-C. The results suggest that curcumin may
represent a treatment option for irritable bowel syndrome-C
through modulation of the gut microbiota and relevant
neurotransmitters. Our results support the possibility of using
curcumin to treat irritable bowel syndrome-C patients.
The
impact of ginger and curcumin on diabetic nephropathy induced by
streptozotocin in rats European Journal of
Translational and Clinical Medicine | January 2024 Curcumin
is a potent component in herbal medicine and is extensively
studied for various health conditions. Its primary compound,
polyphenol curcumin, exhibits powerful anti-inflammatory,
antioxidant, and anticarcinogenic properties. In diabetes
management, curcumin’s effectiveness lies in its interaction
with key molecules and pathways crucial in the disease’s
progression. Studies show curcumin’s ability to alleviate
insulin resistance, a factor in metabolic syndrome. Both ginger
and curcumin contain antioxidants that activate redox-sensitive
transcription factors, bolstering cellular antioxidant defenses.
Given the importance of dietary management in diabetes,
interventions using natural substances like ginger and curcumin
offer promising strategies to mitigate the renal complications
of DM. Ginger and curcumin extract contained the highest
phytochemical content and anti-oxidant activity (AOA). The
high glycoside content was recorded in curcumin. The high
terpene content was recorded in curcumin extract. The highly
alkaloid content was recorded in curcumin extract. Our results
demonstrated the anti-inflammatory and the antioxidant effects
of ginger and curcumin extracts, administered individually or in
combination. Our data have also shown that ginger and curcumin
extracts helped manage STZ-induced diabetic nephropathy and
oxidative stress via significant suppression of the NF-κB gene
expression. These extracts possess anti-inflammatory potential
by suppressing inflammatory cytokines and modulators through the
suppression of redox-based NF-κB activation.
Evaluating the potential of Vitamin D and curcumin
to alleviate inflammation and mitigate the progression of
osteoarthritis PLoS One | January 2024
This study, for the first time, provides evidence of the
mitigating effect of Vitamin D and curcumin on PAR-2 mediated
inflammation. Nutraceuticals, such as Vitamin D and curcumin,
present potential therapeutic alternatives, offering
anti-inflammatory effects, potentially addressing osteoarthritis
inflammation. This study presents robust evidence that Vitamin D
and curcumin might represent a pioneering, natural, and
efficacious therapeutic strategy for managing osteoarthritis and
mitigating its related symptoms, specifically those exacerbated
by PAR-2 signaling. In conclusion, our study demonstrates that
both Vitamin D and curcumin can attenuate the pro-inflammatory
response in chondrocytes by inhibiting PAR-2 signaling, reducing
the expression of TNF α, IL 6, and IL 8, as well as the
RANKL/RANK system. Moreover, these bioceuticals also reduce IFN
γ expression, which amplifies the inflammatory events in OA.
These findings suggest that Vitamin D and curcumin have
potential therapeutic benefits in the management of
osteoarthritis.
The
impact of ginger and curcumin on diabetic nephropathy induced by
streptozotocin in rats European Journal of
Translational and Clinical Medicine | January 2024 Our
results demonstrated the anti-inflammatory and the antioxidant
effects of ginger and curcumin extracts, administered
individually or in combination. Our data have also shown that
ginger and curcumin extracts helped manage STZ-induced diabetic
nephropathy and oxidative stress via significant suppression of
the NF-κB gene expression. These extracts possess
anti-inflammatory potential by suppressing inflammatory
cytokines and modulators through the suppression of redox-based
NF-κB activation. Our findings indicate that ginger and curcumin
extracts have therapeutic potential in mitigating functional and
structural alterations in the kidneys of diabetic rats, possibly
due to their anti-diabetic and anti-inflammatory properties.
Rats treated with combined ginger and curcumin extracts had
superior outcome in terms of more antioxidant activity, better
glycemia management and less DN-related kidney damage (reduced
albuminuria and less histological changes). Ginger and curcumin
are two well-known functional foods from the Zingiberaceae
family that have anti-inflammatory qualities. Curcumin is a
potent component in herbal medicine and is extensively studied
for various health conditions. Its primary compound, polyphenol
curcumin, exhibits powerful anti-inflammatory, antioxidant, and
anticarcinogenic properties. In diabetes management, curcumin’s
effectiveness lies in its interaction with key molecules and
pathways crucial in the disease’s progression. Studies show
curcumin’s ability to alleviate insulin resistance, a factor in
metabolic syndrome. Both ginger and curcumin contain
antioxidants that activate redox-sensitive transcription
factors, bolstering cellular antioxidant defenses. Given the
importance of dietary management in diabetes, interventions
using natural substances like ginger and curcumin offer
promising strategies to mitigate the renal complications of
diabetes.
Therapeutic
Potential of Curcumin, a Bioactive Compound of Turmeric, in
Prevention of Diabetes through the Modulation of Oxidative
Stress and Inflammation Molecules | January
2024 In physiological and biochemical studies, it was found
that curcumin decreases glucose, creatinine, urea, and
inflammatory markers and increases antioxidant enzyme levels. In
addition, the histopathological findings revealed that curcumin
plays a significant role in the maintenance of renal tissue
architecture through the reduction in all pathological changes.
This study showed that curcumin has a vital role in the
regulation of the expression pattern of the IL-6 protein and
fibrosis. Based on biochemical and histopathological findings,
this study delivers a scientific suggestion that curcumin could
be a suitable remedy in the management of diabetes mellitus. The
novelty of the current study is that curcumin showed
anti-fibrotic potential by reducing collagen fiber deposition.
Curcumin treatment showed a significant decrease in parameters
and an increase in insulin level as compared to negative control
rats. Oral administration of curcumin significantly ameliorated
changes. Hence, based on biochemical and histopathological
findings, this study delivers a scientific suggestion that
curcumin could be a suitable remedy in the management of
diabetes mellitus. Curcumin, a yellow-colored compound, is
produced by plants of Curcuma longa species, and it is
chemically known as 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,
6-heptadiene-3, 5-dione. It possesses antioxidant,
anti-inflammatory, anti-tumor, and other biological activities.
Curcumin is capable of exercising its antioxidant action via
scavenging a variety of hydrogen peroxide and nitric oxide (NO)
radicals and reactive oxygen species (ROS) as superoxide
radicals and by preventing lipid peroxidation. Moreover, several
in vitro as well as in vivo studies have described that curcumin
has potential for treating numerous inflammatory diseases.
Curcumin significantly reduced blood urea nitrogen, serum levels
of urea, and creatinine and simultaneously reduced
albumin/protein urea and increased creatinine clearance.
Further, it also prevented damage to renal tubules and the
thickness of the basement membrane. Curcumin treatment
efficiently counters diabetes-induced oxidative-stress-mediated
hepatic damage. Another finding reported that curcumin improved
the survival as well as the function of islet cells, with
reduced cell apoptosis in the islet of Langerhans and increased
insulin secretion in the STZ-induced diabetic model.
Exploring the Potential of Curcumin in Preserving
Telomere Length: A New Frontier in Cellular Aging and Health
Medium | January 2024 Curcumin has been valued for centuries
for its medicinal properties, particularly its potent
antioxidant and anti-inflammatory effects. Recent studies have
explored the potential of curcumin in influencing the length and
maintenance of telomeres, providing insights into its possible
role in combating cellular aging. Curcumin's role in preserving
telomere length largely hinges on its antioxidant properties.
Oxidative stress, a result of an imbalance between free radicals
and antioxidants in the body, is a key factor in the
acceleration of telomere shortening. Curcumin, with its strong
antioxidant capacity, helps neutralize these free radicals,
potentially reducing the rate of telomere shortening and thereby
promoting cellular longevity. In addition, the anti-inflammatory
properties of curcumin might help mitigate damage, thereby
slowing down the rate of telomere attrition. This could be
particularly significant in the context of chronic diseases and
age-related conditions where inflammation plays a pivotal role.
One of the most intriguing aspects of curcumin's relationship
with telomeres is its potential effect on the activity of
telomerase. Some studies have shown that curcumin might
stimulate telomerase activity, thus aiding in the maintenance
and even extension of telomere length. This suggests a possible
direct intervention in the cellular aging process. The
implications of curcumin's effects on telomeres extend to the
prevention and management of various diseases. Age-related
diseases like cancer, neurodegenerative diseases, and
cardiovascular problems have been linked to telomere length.
Therefore, by preserving telomere length, curcumin could
potentially play a role in mitigating these conditions. Its
antioxidant and anti-inflammatory properties, combined with its
potential to impact telomerase activity, make it a compound of
significant interest in the fields of aging and disease
prevention. In the realm of medicine, the exploration of
curcumin's role in telomere biology could lead to novel
therapeutic strategies. For instance, it could be employed as
part of a regimen for diseases where telomere shortening plays a
key role.
The
effect of curcumin on the necroptosis signaling pathway in colon
cancer cells Bulletin of Biotechnology |
January 2024 Curcumin, a yellow compound isolated from the
turmeric plant, is important in preventing cancer. Studies have
shown that curcumin has an anticancer effect by driving cancer
cells into apoptosis, but studies showing its effect on
necroptosis are inconclusive. Consequently, the current data
clearly suggest that curcumin is a prominent driver of
necroptotic signaling-mediated colon cancer cell death.
Accumulating mass of indication suggests that curcumin has
antioxidant, anti-inflammatory, anti-bacterial, anti-diabetic,
and anti-cancer activities (Selvam et al. 2019). Curcumin has
shown to have significant impact on many signaling pathways in
cancer cells, which controls various cellular activities. The
anticancer activities of curcumin have also been shown in colon
cancer cells (Selvam et al. 2019). Curcumin has been
demonstrated to show anti-cancer activity in HT-19 colon cancer
cells by suppressing colony formation, cell viability, and DLEC1
promoter methylation (Guo et al. 2015). In addition, curcumin
has been shown to suppress the level of ATG5 (autophagy related
5) protein in HCT-116 cells, leading to the suppression of
autophagosome formation, cellular senescence, and cell cycle
arrest (Mosieniak et al. Bull Biotechnol (2023). In addition,
studies have shown that curcumin has anticancer activity in
other colon cancer cells such as Caco-2, HCT-15, and SW620 (Selvam
et al. 2019). Curcumin, which is extracted from the plant
Curcuma longa, is known to have numerous biological and
pharmacological activities. Curcumin has been reported to
stimulate cell death pathways such as apoptosis, autophagy, and
pyroptosis in many different cancer cells. In a study by
Blakemore et al., curcumin was shown to disrupt the cell cycle
progression by inducing G2/M cell cycle arrest in various colon
cancer cells (Blakemore et al. 2013). In addition, curcumin
treatment has been shown to cause abnormal mitotic spindle
formation and DNA damage. In addition, curcumin has been shown
to dose- dependently suppress cell proliferation. Bull
Biotechnol (2023). Remarkably, in our study, curcumin was shown
to stimulate necroptosis by increasing the expression of RIPK1,
RIPK3, and MLKL genes, especially in HT -29 colon cancer cells.
In conclusion, present findings strongly indicates that curcumin
is a significant driver of colon cancer cell death mediated by
necroptotic signaling.
Curcumin inhibits the invasion and migration of
pancreatic cancer cells European Journal
of Nutrition | December 2023 Curcumin is a natural
polyphenolic compound with wide-ranging pharmacological effects.
Growing evidence suggests that curcumin has anticancer activity
against pancreatic cancer, but the mechanism remains
incompletely elucidated. Curcumin increased the expression of
TFPI-2 mRNA and protein in pancreatic cancer cells and
attenuated cell invasion and migration. Curcumin also inhibited
ERK and JNK pathways and EMT in pancreatic cancer cells.
Knockdown of TFPI-2 partially reversed the inhibition of ERK and
JNK pathways and EMT by curcumin. Mechanistically, curcumin
upregulated TFPI-2, thereby inhibiting the ERK and JNK pathways,
leading to the inhibition of EMT in pancreatic cancer cells.
Collectively, curcumin inhibits ERK- and JNK-mediated EMT
through upregulating TFPI-2, which in turn suppresses the
migration and invasion of pancreatic cancer cells. These
findings provide new insights into the antitumor mechanism of
curcumin.
Curcumin modulates cell type-specific miRNA networks
to induce cytotoxicity in ovarian cancer cells
Life Sciences | December 2023 Curcumin, a natural
polyphenolic compound extracted from the rhizomes of the
culinary spice turmeric (Curcuma longa), has proven
anti-cancer activity against various human cancers and has
entered into Phase III clinical trials as monotherapy and in
combination therapies for colon (NCT00295035), prostate
(NCT03769766, NCT02064673), and pancreatic cancers
(NCT00486460). Besides anti-cancer activity, it also exhibits
antioxidant, anti-aging, anti-inflammatory, anti-microbial,
anti-proliferative, and anti-angiogenic properties. Curcumin
exerts such diverse therapeutic properties by interacting and
modulating multiple molecular targets, and signaling cascades.
Curcumin effectively induces cytotoxicity in many ovarian cancer
cell lines and its role as an epigenetic modulator by activating
multiple miRNAs in ovarian cancers has been studied. Taken
together, in this study, we report a cell-type specific
epigenetic role of curcumin, highlighting the distinct miRNAs
modulated within the two molecularly distinct ovarian cancer
cell lines to render cytotoxicity.
The effects of curcumin-piperine supplementation on
inflammatory, oxidative stress and metabolic indices in patients
with ischemic stroke in the rehabilitation phase: a randomized
controlled trial Nutrition Journal |
December 2023 In the present study, curcumin-piperine
supplementation was associated with a significant improvement in
physical functioning, role functioning/physical, energy/fatigue,
emotional well-being, and social functioning. Moreover, curcumin
caused less increase in pain compared with the control group.
Curcumin-piperine supplementation had beneficial effects on
CIMT, serum hs-CRP, TC, TG, TAC, and systolic and diastolic
blood pressure in patients with ischemic stroke in the
rehabilitation stage. Curcumin has been shown to serve as a
promising factor for preventing stroke and improving its
complications in animal studies. Curcumin has many
pharmacological activities that are relevant to the treatment of
stroke. Preclinical studies have shown the protective effects of
curcumin against stroke due to the anti-inflammatory and
antioxidant, and anti-ischemic properties of the molecule.
Studies showed that apoptosis during ischemia/reperfusion plays
an important role in stroke-related brain damage. Curcumin
exerts its neuroprotective effect by regulating cell apoptosis
and increasing neurogenesis. Animal studies have shown that
post-stroke administration of curcumin can significantly reduce
lipid peroxidation, mitochondrial dysfunction, glial activation,
and infarct volume. In addition, curcumin improves cognitive
deficits and motor activity.Despite its high therapeutic
potential, curcumin is limited for medical purposes due to its
low aqueous solubility, low bioavailability, and rapid
degradation. To improve its pharmacokinetic features,
co-administration of curcumin with piperine has been introduced
as an alternative. Piperine, which is a naturally occurring
alkaloid from pepper, has been shown to increase the
bioavailability of curcumin and reduce its glucuronidation. It
seems that curcumin has several unique properties to improve the
health condition of patients with ischemic stroke. The present
study showed a decrease in systolic and diastolic | Deblood
pressure after 12 weeks of curcumin-piperine supplementation in
comparison to placebo. It is suggested that the effect of
curcumin on lowering blood pressure is applied through the
effect on antioxidant activity and vascular function of this
phytochemical. We found that curcumin-piperine intake can lower
serum TC and TG concentrations. Other results in this study
showed that curcumin-piperine supplementation decreased weight
and waist circumference compared with the control group. Results
of the current study indicated that curcumin-piperine
co-supplementation has beneficial effects on CIMT, systolic and
diastolic blood pressure as well as serum levels of hs-CRP, TC,
TG, and TAC.
Curcumin/Turmeric Supplementation Could Improve
Blood Pressure and Endothelial Function
Clinical Nutrition ESPEN | December 2023 A number of studies
have examined the impact of curcumin/turmeric on blood pressure
and the factors allegedly responsible for hypertension. In this
systematic review and meta-analysis, we tried to sum up the
existing literature on randomized controlled trials
investigating this hypothesis. Our findings suggested that
curcumin/turmeric supplementation significantly improved
systolic blood pressure (SBP), diastolic blood pressure (DBP),
blood levels of vascular cell adhesion molecule-1 (VCAM-1), and
flow-mediated vasodilation (FMD). Curcumin/turmeric
supplementation could be regarded as a complementary method to
improve blood pressure and endothelial function.
Antioxidant curcumin induces oxidative stress to
kill tumor cells
Oncology Letters | December 2023 Curcumin is a plant
polyphenol in turmeric root and a potent antioxidant. It binds
to antioxidant response elements for gene regulation by nuclear
factor erythroid 2‑related factor 2, thereby suppressing
reactive oxygen species (ROS) and exerting anti‑inflammatory,
anti‑infective and other pharmacological effects. Of note,
curcumin induces oxidative stress in tumors. Curcumin is a plant
polyphenol in the rhizome of turmeric and was classified as a
third‑generation cancer chemopreventive agent by the National
Cancer Institute. Several studies have reported anticancer
mechanisms mediated by curcumin through the induction of
elevated ROS. Curcumin has anti‑inflammatory, antibacterial,
hepatoprotective and anticancer properties, and its anticancer
effects have been reported in several tumor types. In melanoma,
curcumin has been reported to increase the ROS level and
activate oxidative stress in the cysteine asparaginase pathway,
which causes tumor cell death. A recent study reported that
curcumin downregulated ubiquitin‑specific peptidase 4 to
modulate lysosome‑associated membrane protein 3, and thus
inhibited the malignant progression of colorectal cancer cells.
Furthermore, curcumin‑induced accumulation of ROS in tumors to
kill tumor cells has been noted in several studies as discussed
in the present review. Curcumin is well tolerated by humans. For
example, a study that evaluated the toxicity of curcumin in
humans reported that subjects administered 8 mg/day curcumin did
not develop toxicity. Curcumin is a natural compound that has
been used for the treatment of numerous types of diseases, such
as Alzheimer's disease, fatty liver and cancer. Of note,
curcumin has a dual role in oncological and non‑oncologic
diseases. Specifically, in non‑neoplastic diseases, curcumin is
a potent antioxidant that attenuates oxidative stress and
mitochondrial damage. In conclusion, curcumin may have the
potential to become a cutting‑edge drug for the treatment of
tumors and other diseases.
Anti-inflammatory
effect of curcumin in an accelerated senescence model of Wistar
rat: an in vivo and in-silico study Journal
of Biomolecular Structure and Dynamics | December 2023
Curcumin, a biphenolic substance derived from turmeric (Curcuma
longa), offers a number of health-beneficial effects, including
anti-inflammatory, cardiovascular protection, anti-cancerous,
and anti-angiogenic. Our study provides convincing support for
the idea that eating a diet high in curcumin may help to reduce
inflammation and help to explain some of its health-beneficial
effects.
Curcumin: a bioactive compound with molecular
targets for human malignancies Food and
Agricultural Immunology | December 2023 Curcumin has
anticancer activity including inducing apoptosis and inhibiting
proliferation and invasion of tumours by suppressing a variety
of cellular signalling pathways. It also possesses anti-tumour
activity on different human cancers such as breast cancer, lung
cancer, head and neck squamous cell carcinoma, prostate cancer,
and brain tumours. In vitro and in vivo trails, curcumin
inhibits tumour development and metastasis by inhibiting many
pathways that regulate signalling in malignant cells, including
Ras, p53, extracellular signal-regulated kinases (ERK),
Wnt-protein kinase B (Akt), MAPKs, and PI3K. Curcumin can also
inhibit IKK, EGFR, -catenin, cyclin D1, tumour necrosis factor
(TNF), and anti-apoptotic genes such as Bcl-X and Bcl-2 along
with downregulating nuclear transcription factors like NF-κB,
which reduces the formation of pro-inflammatory cytokines like
chemokines, TNF-, Interleukins and IL-1, IL-2, IL-6, IL-8,
IL-12. Curcumin, which comes from the rhizome herb Curcuma
longa as well, is renowned as turmeric, it has a polyphenolic
composition and it owns a vast range of biological tasks
involving antioxidant, anti-inflammatory, hepato-protective,
immunomodulatory, anti-depressant, anti-dyslipidemic,
antidiabetic, analgesic, and defensive factors against pulmonary
diseases. Of specific concern, there have been various studies
proposing the effectiveness of curcumin as a chemo protective
anti-carcinogenic, and chemo-sensitizing complex besides a
variation of cancer forms. The novelty of using curcumin as an
anti-cancerous agent lies in its unique ability to target
multiple cancer cell signalling pathways by inducing apoptosis,
suppressing cell proliferation, inhibiting inflammation and
blocking angiogenesis. As evident from the studies, curcumin
preferentially kills tumour cells through the control of several
cell signalling pathways, according to many in vivo animal
studies and in vitro cell cultures. Many studies showed that
curcumin's anticancer activity is related to the activation of
apoptosis via interference with cell viability signalling
pathways. Previous studies have also shown that caspase is
involved in curcumin-induced apoptosis. CUR has been shown to
trigger caspase-3-independent cell death in human
multidrug-resistant cells. Whilst it is not apparent if curcumin
can produce ROS or has antioxidant potential, research has shown
that curcumin-caused ROS generation and curcumin-induced ROS
ultimately result in autophagy activation in cancerous cells.
Moreover, curcumin was shown to activate JNK and reduce NF-kB,
indicating that these components are implicated in
curcumin-induced ROS formation and apoptosis. Findings suggested
that curcumin-induced apoptosis is a pro-death signal instead of
a pro-survival signal. According to the findings, it was
proposed that curcumin induces autophagy in glioma cells to show
anticancer activity instead of eliciting a cytoprotective
reaction. Since curcumin induces autophagic cell death and can
inhibit cell growth, it might be an effective therapeutic drug
for cancer therapies. As a polyphenolic, natural substance, it
has generated interest as a possible cancer chemotherapeutic
agent.
Effects of curcumin on non-alcoholic fatty liver
disease: a scientific study
Phytomedicine | November 2023 Curcumin can alleviate insulin
resistance, inhibit oxidative stress response, reduce
inflammation, reduce liver fat deposition, and effectively
improve NAFLD through various modalities, inhibiting the
progression into cirrhosis and fibrosis. The review observed
that curcumin can activate various signaling pathways such as
AMPK and NF-κB to inhibit oxidative stress and apoptosis,
thereby reflecting its pharmacological effects: lowering lipid,
anti-inflammatory, reducing insulin resistance, and
anti-fibrosis. Curcumin also can potentially serve as a primary
regulatory target for treating hepatic steatosis using gut
microbiota. Curcumin has been found to have a variety of
anti-inflammatory, antioxidant, and antitumor effects and
affects the lipid metabolism in NAFLD mouse models. In recent
years, curcumin has been found to alleviate IR, inhibit the
oxidative stress response, reduce inflammation, reduce liver fat
deposition, and effectively improve NAFLD through various
modalities, blocking the progression into cirrhosis and
fibrosis.
Targeting endothelial cells with golden spice
curcumin: A promising therapy for cardiometabolic multimorbidity
Pharmacological Research | November 2023 Curcumin shows
promise as a potential treatment option for cardiometabolic
multimorbidity, particularly due to its ability to target
endothelial cells. It represents a novel and natural lead
compound that may offer significant therapeutic benefits in the
management of cardiometabolic multimorbidity. Curcumin, derived
from the golden spice Curcuma longa and widely used as
a dietary supplement, possesses anti-inflammatory, analgesic,
anti-angiogenic and anti-oxidative properties. Several studies
have demonstrated that the therapeutic effects of curcumin
against cardiometabolic multimorbidity were attributed to its
ability to target ECs. Piperine, for instance, has been found to
increase the bioavailability of curcumin significantly.
Curcumin, a natural compound derived primarily from, the
rhizomes of Curcuma longa, possesses significant
pharmacological properties. Notably, as a golden spice, it is
widely used in functional foods and dietary supplements.
Extensive studies have confirmed its high oral safety, and
mature extraction and synthesis methods are available for
large-scale production. Additionally, our review has highlighted
the tremendous potential of curcumin in the treatments a
majority of cardiometabolic multimorbidity by the alleviation of
endothelial damages. Furthermore, research studies have
demonstrated the potential of curcumin in alleviating
endothelial inflammation, oxidative stress, and cellular
inflammation caused by diverse pathological conditions, such as
hyperglycemia, hyperlipidemia, hypertension, atherosclerosis,
cerebral ischemia, and myocardial infarction. Our literature
review highlights that the pharmacological effects of curcumin
pertain to multiple critical signaling pathways such as
NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1β, and ROS-ERK1/2. Its effects
are also associated with the modulation of HO-1, MDA, NOs, VEGF,
ICAM-1 and ROS levels.
Curcumin and analogues in mitigating liver injury
and disease consequences: from molecular mechanisms to clinical
perspectives Phytomedicine | November 2023
Curcumin demonstrates significant therapeutic potential across
various medical conditions, particularly emerging as a promising
candidate for liver injury treatment. Curcumin boasts remarkable
antioxidant properties by neutralizing free radicals and
modulating oxidative stress. Curcumin and its analogs have
demonstrated low toxicity in vitro and in vivo. Curcumin plays a
role in alleviating liver injury by modulating the antioxidant
system, as well as cellular and molecular pathways. Curcumin,
belonging to the polyphenol class, is a bioactive compound of
turmeric (Curcuma longa). It is recognized as a dietary
chemoprotective compound, and has properties such as preventing
oxidative damage, reducing inflammation, neuroprotection,
nephroprotection, hepatoprotection, anti-proliferation, and
anti-metastatic effects (Nabavi et al., 2014; Zhao et al.,
2023). These functional characteristics endorse its potential as
an alternative solution for treating liver injury. Pooled
randomized controlled trials indicate that curcumin might have a
positive impact on fatty liver by enhancing metabolic indicators
and anthropometric measurements (Baziar and Parohan, 2020; White
and Lee, 2019). Curcumin and its extracts have the potential to
be modified into various analogs. Curcumin emerges as a
promising phytomedicine for liver injury owing to its
effectiveness in hepatoprotection and low toxicity profile.
Curcumin is essential for controlling the liver microenvironment
by impacting the complex processes related to the production.The
antioxidant, anti-inflammatory, and hepatoprotective properties
of curcumin and similar compounds have been acknowledged, making
them potential therapeutic agents (Ahmad et al., 2019; Alhusaini
et al., 2018; Zhou et al., 2007). They effectively prevent and
mitigate liver injury through mechanisms that target tissue
cells, metabolic pathways, and the extracellular matrix.
Anti-cancer and Anti-angiogenic Effects of Curcumin
and Epigallocathechin-3-Gallate in a Mouse Model of Renal Cancer Medicine
and Pharmacology, Oncology and Oncogenics | November 2023
Results have shown that curcumin, a component of turmeric (Curcuma
longa), and epigallocatechin-3-gallate (EGCG), found in
Camelia sinensis, are able to synergistically inhibit cell
survival, proliferation and angiogenesis of several types of
cancer, including renal carcinoma, as shown in our results, by
modulating different signaling pathways. Furthermore,
pretreatment of mice with a diet containing 0.6% curcumin prior
to ccRCC injection showed significant inhibition of tumor
engraftment in 60%. Taken together, our data indicate, for the
first time, that the combination of curcumin and EGCG acts in a
synergistic manner to inhibit the growth and angiogenesis of
ccRCC and with less toxicity than sunitinib and provide an
important rationale for future clinical development for
chemoprevention and treatment of renal cancer. With our results,
we can strongly support the hypothesis that the combination of
curcumin and EGCG acts in a synergistic manner to inhibit the
growth and angiogenesis of ccRCC, suggesting a possible
implication for new therapeutic strategies for the treatment of
patients with ccRCC. In this work we demonstrate
antiproliferative, antiangiogenic and synergistic effects of
some natural compounds as Curcumin and EGCG major active
ingredient of green tea for the care of renal cancer. The
combination of curcumin and EGCG may produce a better antitumor
effect as showed in our data. In summary, our results indicate
that the combination of EGCG plus Curcumin show the same effects
of tumor growth delay and angiogenesis reduction in an initial
phase compared to Sunitinib treated mice. Interestingly, however
natural compounds show a longer lasting effect. The antitumoral,
antiangiogenic and drug sensibility of the combination of
curcumin and EGCG, encourage their wider use in cancer
therapy confirming their synergism of action and low toxicity.
Interestingly, these natural compounds can be easily taken
orally by the population without any side effects, and this is
an important advantage in terms of cancer prevention.
The chemotherapeutic potential and epigenetic
regulation of curcumin in lung cancer: a mini review
Naunyn-Schmiedeberg's Archives of Pharmacology | November 2023
In-depth research has been done on curcumin as a multi-target
anti-tumor and anti-inflammatory molecule. A pharmacologically
active polyphenol produced from turmeric is called curcumin.
Over the past few decades, curcumin’s therapeutic potential has
been thoroughly studied, and data indicate that curcumin may
play a part in a variety of biological processes, most notably
its potent anticancer activity. Being a pleiotropic chemical,
curcumin regulates a variety of molecules that are key players
in many cell signaling pathways. It has been shown to stifle
transformation, restrain proliferation, and trigger apoptosis.
Curcumin can reduce the development of non-small cell LC by
downregulating Circular RNA hsa_circ_0007580, which in turn
controls the expression of integrin subunit beta 1 by adsorbing
miR-384.
Curcumin alleviates Alzheimer’s disease by
inhibiting inflammatory response, oxidative stress and
activating the AMPK pathway Journal of
Chemical Neuroanatomy | November 2023 Curcumin not only
improved cognitive function and spatial memory, but also
alleviated the pathological damage and apoptosis of brain
tissues for Alzheimer’s disease mice. Meanwhile, upon curcumin
treatment, the number of damaged neurons in Alzheimer’s disease
mice was decreased, the level of Aβ1-42 in Alzheimer’s disease
mice was significantly decreased. Furthermore, the Alzheimer’s
disease mice treated with curcumin exhibited lower TNF-a, IL-6,
IL-1β and MDA levels and a higher SOD content. Besides, curcumin
also downregulated p65 expression and upregulated AMPK
phosphorylation. Curcumin (Cur) is one of the main active
ingredients of turmeric (Kim et al., 2019). Curcumin exhibits
many pharmacological effects, such as anti-inflammatory (Lee et
al., 2020), anti-oxidation (Theppawong et al., 2019) and
neuroprotective actions (Rasouli and Ghavami, 2020). Curcumin
has been reported to attenuate spatial memory impairment in
Wistar rats by exerting anti-inflammatory, anti-apoptosis, and
anti-oxidative properties (Hadizadeh-Bazaz et al., 2021). In
addition, curcumin can protect the hippocampus from ischemic
insult by suppressing the activation of inflammasome via the
modulation of AMPK (Li et al., 2015). Curcumin has been used for
the treatment of many diseases, particularly those associated
with inflammation and oxidative stress (Mohammad Pour et al.,
2019, Alizadeh and Kheirouri, 2019). For example, curcumin and
its analog have been reported to attenuate inflammation and
oxidative stress in the brain tissues of the diabetes mellitus
rat models (Miao et al., 2021). Furthermore, Chen et al. have
provided substantial evidence that curcumin exerts its
neuroprotective effects in animal models of traumatic brain
injury by inhibiting the inflammatory response and oxidative
stress (Chen et al., 2023). Consistent with previous studies, in
this study, we observed that treatment with curcumin not only
reduced the levels of inflammatory factors in the serum and
hippocampus, but also decreased oxidative stress. In conclusion,
this study has revealed the effect and mechanism of curcumin in
Alzheimer’s disease, and verified our hypothesis that curcumin
may impede the development of Alzheimer’s disease by inhibiting
inflammatory response, oxidative stress and activating the AMPK
pathway. Curcumin improved learning and memory abilities in
Alzheimer’s disease mice. Curcumin ameliorated the spatial
working memory in Alzheimer’s disease mice. Curcumin alleviated
the pathological damage of brain tissues in Alzheimer’s disease
mice. Curcumin enhanced the number of damaged neurons in
Alzheimer’s disease mice. Curcumin suppressed the apoptosis of
brain tissues in Alzheimer’s disease mice. Curcumin reduced
Aβ1-42 deposition in Alzheimer’s disease mice. Curcumin
inhibited inflammatory response and oxidative stress in
Alzheimer’s disease mice. Curcumin exerted a protective effect
on Alzheimer’s disease mice via activation of the AMPK pathway.
The findings of the study shed some new light on the treatment
of Alzheimer’s disease and the application of curcumin.
Oxidative Stress and Cancer: Harnessing the
Therapeutic Potential of Curcumin and Analogues Against Cancer
European Journal of Biology | November 2023 The phytochemical
Curcumin has gained ground as an interesting cancer therapeutic.
Curcumin is an active phenolic compound used in traditional
medicine around the world. Curcumin is involved in a
plethora of clinical trials touching on a wide range of cancers.
Taking advantage of curcumin’s innate antioxidant and
anti-cancer abilities clinical trials are observing improvements
in recurrence-free survival in pancreatic cancer, safety and
tolerability in metastatic treatment-resistant colorectal
cancer, tumor-induced inflammation reduction in endometrial
carcinoma, and efficacy and bioavailability in glioblastoma.
Curcumin has a history of use in medicines in Asian countries
where it was used as an anti-inflammatory and anti-dysenteric,
and has recently shown antioxidant properties in the context of
various disease instances. Curcumin has become a popular drug
for cancer therapy over the last few decades and multiple
analogs have arisen based on curcumin structure.
Mechanistically, curcumin has shown the ability to regulate a
plethora of molecular targets lending to its anti-cancer
properties. The transcription factor NF-kB is one of the longest
known targets of curcumin and its suppression in a variety of
cancers including leukemia and melanoma. Natural compounds like
curcumin are especially advantageous in this aspect due to their
low toxicity towards healthy cells.
Curcumin Disrupts a Positive Feedback Loop between ADMSCs and
Cancer Cells in the Breast Tumor Microenvironment
Pharmaceutics | November 2023 Our study showed that curcumin
is a potent anti-cancer agent that can remodel the breast tumor
microenvironment, thereby restricting the ADMSC-cancer positive
feedback loop associated with the CXCL12/CXCR4 axis. Curcumin is
a natural polyphenolic compound derived from a turmeric plant (Curcuma
longa). Its therapeutic effects against cancer have been
well-documented, showing anti-cancer, anti-oxidative, and
anti-inflammatory effects. Moreover, previous studies have
suggested that curcumin can interfere with the metastasis of
cancer cells by inhibiting the CXCL12/CXCR4 axis. We induced
ADMSC transformation and verified that curcumin diminished the
phenotypic change, inhibiting CAF marker expression.
Additionally, curcumin suppressed the CXCL12/CXCR4 axis and its
downstream signaling both in ADMSCs and MCF7 cells. The CM from
ADMSCs, whose ADMSC-to-CAF transformation was repressed by the
curcumin treatment. Through our research, it was demonstrated
that curcumin is an effective modulator of breast TME. By
disrupting the CXCL12/CXCR4 axis and the following NF-κB
signaling pathway and EMT, curcumin alleviated the disease by
mitigating the progression and metastasis of MCF7 and finally
suppressing the positive loop formation within breast tumor
microenvironment. These findings provide valuable insights into
the therapeutic applications of curcumin and other flavonoids in
treating cancer effectively in terms of tackling the tumor
microenvironment.
Effects of curcumin/turmeric supplementation on the
liver enzymes, lipid profiles, glycemic index, and
anthropometric indices in non-alcoholic fatty liver patients: An
umbrella meta-analysis Phytotherapy
Research | November 2023 Findings of 11 meta-analyses of 99
randomized controlled trials comprising 5546 participants
revealed that curcumin/turmeric supplementation reduced AST
(ES = −1.072, 95% CI (−1.656, −0.488), p = 0.000), ALT
(ES = −0.625, 95% CI (−1.170, −0.134), p = 0.014), and TG
(ES = −0.469, 95% CI (−1.057, 0.119), p = 0.128) levels, and
HOMA-IR (ES = −0.291, 95% CI (−0.368, −0.214), p = 0.000), BMI
(ES = −0.205, 95% CI (−0.304, −0.107), p = 0.000), and WC
(ES = −1.290, 95% CI (−2.038, −0.541), p = 0.001) in comparison
to the control group. The findings suggest the beneficial
effects of curcumin/turmeric supplementation in patients with
NAFLD, such as improving liver function, decreasing serum TG
levels, ameliorating insulin resistance, and reducing general
and central obesity.
Apoptosis antagonizing transcription factor-mediated
liver damage and inflammation to cancer: Therapeutic
intervention by curcumin in experimental metabolic dysfunction
associated steatohepatitis-hepatocellular carcinoma
Journal of Cellular Physiology | November 2023 Curcumin
treatment also suppressed hepatic expression of inflammatory,
fibrogenic, and oncogenic markers. Of note, there was a
significant reduction in the expression of AATF upon curcumin
treatment in WDSW/CCl 4 mice and human HCC cells. In contrast,
curcumin upregulated Kruppel‐like factor 4 (KLF4) in MASH liver
and HCC cells, which is known to downregulate sp1 (specificity
protein‐1) expression. Thus, curcumin treatment effectively
inhibited the progression of MASH to HCC by downregulating the
expression of AATF via the KLF4‐Sp1 signaling pathway. These
preclinical findings establish a novel molecular connection
between curcumin and AATF in reducing hepatocarcinogenesis, and
provide a strong rationale for the development of curcumin as a
viable treatment for MASH‐HCC in humans.
Curcumin's Dose-Dependent Attenuation of Gastric
Cancer Cell Progression Via the PI3K Pathway Blockade
Dose-Response | November 2023 Curcumin, a polyphenolic
compound found in turmeric (Curcuma longa), has
demonstrated potential in multiple cancer types due to its
anti-cancer characteristics. Curcumin, the main bioactive
component of turmeric (C longa), has been widely
studied for its anti-inflammatory, antioxidant, and anti-cancer
properties. Mounting evidence suggests that curcumin may
modulate various cellular pathways involved in the initiation,
progression, and metastasis of different cancer types, including
gastric cancer. Curcumin's potential health benefits and
clinical applications cover a broad range of medical conditions,
such as Alzheimer's disease, cardiovascular diseases, and
diabetes, among others. Its anti-cancer effects have been
demonstrated in numerous in vitro and in vivo studies, as well
as in preliminary clinical trials. Curcumin has been found
to exert its anti-cancer activity through several mechanisms,
including apoptosis induction, cell cycle arrest, angiogenesis
inhibition, and suppression of invasion and metastasis.
Emerging evidence suggests that curcumin may inhibit gastric
cancer cell progression by modulating the PI3K signaling
pathway. The study findings demonstrate that curcumin treatment
leads to a significant reduction in gastric cancer cell
proliferation, migration, and invasion. These results are
consistent with previous research on curcumin's anti-cancer
properties in various cancer types. One of the critical
mechanisms by which curcumin may exert its anti-cancer effects
is through the inhibition of the PI3K signaling pathway, which
plays a vital role in regulating cell growth and survival.
Collectively, these studies demonstrate the diverse and
multifaceted mechanisms through which curcumin exerts its
effects on gastric cancer cells. Each study focuses on distinct
signaling pathways, shedding light on different aspects of
curcumin's therapeutic potential. Curcumin, a polyphenolic
compound derived from the turmeric plant (C longa), has
been extensively studied for its health benefits, including
anti-inflammatory, antioxidant, and anti-cancer activities. The
anti-cancer potential of curcumin has been demonstrated in
various cancer types, including gastric cancer. Curcumin has
been shown to inhibit cell proliferation, induce apoptosis, and
suppress angiogenesis, metastasis, and invasion in different
cancer models. The anti-cancer effect of curcumin is attributed
to its multifaceted and intricate molecular mechanisms. Curcumin
exerts its anti-cancer properties by targeting various signaling
pathways involved in cell growth, survival, invasion, and
metastasis. One of its central mechanisms is the inhibition of
the PI3K/Akt/mTOR pathway, which is crucial for cell
proliferation and survival. By blocking this pathway, curcumin
suppresses cancer cell growth and induces apoptosis. Moreover,
curcumin modulates the expression of key genes and proteins
related to cell cycle regulation, such as p53 and
cyclin-dependent kinases (CDKs), leading to cell cycle arrest
and preventing uncontrolled cell division. Curcumin also
exhibits anti-angiogenic effects, inhibiting the formation of
new blood vessels necessary for tumor growth and metastasis.
Additionally, it interferes with various pro-survival and
pro-metastatic molecules, including matrix metalloproteinases
(MMPs), vascular endothelial growth factor (VEGF), and nuclear
factor-kappa B (NF-κB), thus limiting cancer cell invasion and
metastasis. Furthermore, curcumin's antioxidant properties
neutralize free radicals and reduce oxidative stress, which can
contribute to cancer development. Overall, the diverse and
comprehensive mechanisms of curcumin's anti-cancer activity make
it a promising candidate for further exploration and development
in cancer therapy. Our study presents significant clinical
relevance. Curcumin treatment led to a dose-dependent decrease
in cell viability, migration, and invasion in gastric cancer
cells, accompanied by downregulation of key PI3K signaling genes
and proteins. This suggests curcumin's potential as a targeted
therapeutic agent against gastric cancer, particularly when the
PI3K pathway is dysregulated. The dose-dependent nature of
curcumin's effects could allow for targeted inhibition of cancer
cell progression while minimizing adverse effects on normal
cells. In conclusion, the findings from this study suggest that
curcumin may be a promising therapeutic agent for gastric cancer
treatment, partly due to its inhibitory effects on the PI3K
signaling pathway.
Curcumin Attenuates Ferroptosis and Ameliorates
Erectile Function in Diabetic Rats by Activating Nrf2/HO-1
Pathway Andrologia | November 2023
Turmeric-derived polyphenol derivative, curcumin, has been found
to be effective in treating cardiovascular diseases. It has been
found to improve aortic sclerosis by decreasing the production
of peroxides and increasing the expression of the antioxidant
manganese-containing superoxide dismutas. Furthermore, in
experiments involving a high-fat diet, curcumin has been
observed to reduce the increase of vascular oxidative stress
levels caused by the diet. Curcumin treatment has been shown to
be effective in improving erectile function and related tissue
and molecular changes in diabetic rats. Furthermore, in vitro
experiments have confirmed that curcumin can inhibit the
occurrence of ferroptosis in penile endothelial cells that are
stimulated by high glucose through Nrf2/HO-1 signaling. Curcumin
has been found to improve the occurrence of penile ED in
diabetic penile endothelial cells. In recent years, curcumin has
gained popularity in the treatment of vascular diseases due to
its anti-inflammatory and antioxidative properties. Our findings
align with previous studies that have shown curcumin’s ability
to effectively reduce tissue oxidative stress levels and protect
the erectile function of diabetic rats.Furthermore, the results
indicate that curcumin can enhance the erectile function of
diabetic rats by inhibiting ferroptosis in the corpus cavernosum.
Curcumin Induces Apoptosis by Suppressing XRCC4
Expression in Hepatocellular Carcinoma
Nutrition and Cancer | November 2023 Curcumin exerts
anti-cancer effects by inhibiting cell proliferation and
promoting cell apoptosis in hepatocellular carcinoma HCC.
Curcumin is a chemical with various pharmacological activities
used for cancer treatment. It inhibits hepatocellular carcinoma
by inducing apoptosis. Compared with the control group, curcumin
significantly promoted the apoptosis of hepatocellular
carcinoma cells in vitro and in vivo. Immunohistochemical
analysis revealed that curcumin downregulated XRCC4 expression
levels in hepatocellular carcinoma tissues. This may be
due to curcumin interference in the repair process of the
nonhomologous DNA terminal link of hepatocellular
carcinoma cells by downregulating XRCC4 expression.
The Dose-Dependent Effect of Curcumin
Supplementation on Inflammatory Response and Gut Microbiota
Profile in High-Fat Fed C57BL/6 Mice
Molecular Nutrition & Food Research | November 2023 Curcumin,
a polyphenol extracted from Curcuma longa L., exhibits
anti-inflammatory activity. The study aims to investigate the
effects of curcumin supplementation in different doses on the
biochemical profile, inflammatory response, and gut microbiota
profile in mice that are fed with high-fat diet (HFD).Curcumin
increases the IL-10 protein expression in the white adipose
tissue. In the liver, there is a reduction in tumor necrosis
factor alpha (TNF-α) and an increase in IL-10 gene expression.
Also, curcumin promotes the growth of butyrogenic bacteria, such
as Clostridium clusters IV and XIVa.The findings suggest that
curcumin has the potential to improve the inflammatory response
and modulate healthy gut microbiota. Further studies are needed
to clarify the role of curcumin as a preventive and effective
strategy for obesity.
The Potential Mechanism of Curcumin in Treating Oral
Squamous Cell Carcinoma Based on Integrated Bioinformatic
Analysis International Journal of Genomics
| November 2023 Curcumin is a polyphenolic compound derived
from the rhizomes of Curcuma longa, which serves as the primary
bioactive constituent of turmeric. Curcumin has been extensively
used in traditional Chinese medicine to treat various
conditions, such as inflammation, pain, wounds, and
gastrointestinal disorders. Contemporary research has unveiled
many pharmacological properties of curcumin, encompassing
antioxidant, anti-inflammatory, antimicrobial, and anticancer
activities. Importantly, the potential anticancer effect of
curcumin has been explored in diverse cancer types, including
breast, colon, lung, prostate, and Oral Squamous Cell Carcinoma.
Curcumin, the principal constituent of turmeric, has exhibited
potential antitumor properties in clinical trials targeting
malignancies such as hepatic, colorectal, and mammary neoplasms.
In this study, we used a network pharmacology strategy to
explore the potential mechanisms underlying the effect of
curcumin on Oral Squamous Cell Carcinoma.
Antiviral and immunoregulatory effects of curcumin
on coxsackievirus B3-infected hepatitis
Virus Research | October 2023 Curcumin exhibits
anti-inflammatory and antiviral characteristics in inflammatory
and infectious diseases. Several studies suggest that curcumin
exhibits many beneficial pharmacological properties, including
antioxidant, anti-inflammatory, antiangiogenic, and
antimicrobial properties. Curcumin can modulate the nuclear
factor to reduce the oxidative stress in liver injury, diabetes,
nervous system diseases, and pulmonary diseases in vivo (Ghafouri-Fard
et al., 2022; Ke et al., 2020; Liu et al., 2015). It can also
decrease inflammatory levels of cytokines, including TNF-α,
IL-6, and IL-1β, to inhibit tumor invasion and metastasis in
several types of carcinoma and chronic diseases (Giordano and
Tommonaro, 2019; Gonzales and Orlando, 2008). Additionally,
curcumin possesses antiviral activities to inhibit hepatitis C
virus (HCV), enterovirus 71 (EV71), human immunodeficiency virus
(HIV)−1, herpes simplex virus (HSV)−2, and influenza A virus
infections by regulating actin filament organization and
blocking the protein kinase B (Akt) and nuclear factor-κB
(NF-κB) pathways (Dai et al., 2018; Ferreira et al., 2015; Kim
et al., 2010; Qin et al., 2014). Curcumin exhibited
immunoregulatory and antiviral characteristics to reduce
CVB3-induced hepatitis. Curcumin reduced the CPE and liver
enzyme levels of CVB3-infected Huh-7 cells. In the animal
studies, curcumin increased the survival rate and reduced the
clinical severity of CVB3-infected mice. In the liver sections,
we observed that curcumin improved the liver damage induced by
CVB3 infection. Both in vitro and in vivo studies showed that
curcumin can effectively increase HO-1 levels and reduce cleaved
caspase-3 levels in human liver cell lines and the liver of
CVB3-infected mice. Therefore, curcumin is a potential
therapeutic option for CVB3-infected hepatitis clinically.
Evaluation of the protective effects of
curcumin-rich turmeric (Curcuma longa) extract against
isotretinoin-induced liver damage in rats
Toxicology Mechanisms and Methods | October 2023 Our results
showed that ALT, AST, and MDA levels increased, and SOD and GSH
levels decreased in the ISO-administered group compared to the
healthy control group. curcumin 50, 100, and 200 mg/kg groups
were compared to ISO group. A dose-dependent increase in
protective effect was observed. A decrease in ALT, AST, and MDA
levels, and an increase in SOD and GSH levels were determined. A
protective effect was found at all doses. The best protective
effect was in the CRT 200 mg/kg group. Curcumin extract can be
considered a candidate herbal medicine for the elimination of
liver damage in individuals using ISO. However, further
experimental and clinical validation should be studied.
Curcumin and turmeric extract inhibited SARS-CoV-2
pseudovirus cell entry and Spike mediated cell fusion
bioRxiv | October 2023 Turmeric extract (TE)
with curcumin as its main active ingredient has been studied as
a potential COVID-19 therapeutic. Based on our study, both TE
and curcumin are potential inhibitors of SARS-CoV-2 infection at
entry points, either by direct or indirect infection models.
Curcumin can interact with SARS-CoV-2 Spike RBD (Shanmugarajan
et al., 2020), hACE2 (Subbaiyan et al., 2020), and TMPRSS2 as
well (Motohashi et al., 2020). These data align with our
results that curcumin inhibited PSV entry and syncytia
formation. Curcumin is capable of interfering with the
Spike-receptor binding either during direct viral
infection or intercellular transmission, which hinders viral
infection and cell fusion (Marin-Palma et al., 2021). In
addition, TE as the crude extract which contains curcumin also
has the potential to inhibit SARS-CoV-2 infection and
potentially to be developed as an independent
herbal-derived product for prevention of viral infection with
curcuminoids used as identity compounds for TE standardization.
Effects of curcumin/turmeric supplementation on
glycemic indices in adults Diabetes &
Metabolic Syndrome: Clinical Research & Reviews | October 2023
Out of 4182 articles retrieved from the initial search, 59 RCTs
were included. Our findings suggested that turmeric/curcumin
supplementation was significantly effective in improving fasting
blood sugar, fasting insulin levels, and homeostatic model
assessment of insulin resistance. Conclusion Our results
indicate that turmeric/curcumin supplementation can be
considered as a complementary method in the management of
disturbed glycemia.
Effect of Turmeric Herbal on Polycystic Ovary
Syndrome: A Systematic Review International
Journal of Current Science Research and Review | October 2023
One of the herbal medicines to treat PCOS is turmeric or
curcumin. Curcumin has various biological activities including
antioxidant, anti-inflammatory, anti-microbial, anti-tumor,
cardioprotective and neuroprotective effects involving various
mechanisms. Curcumin can stimulate insulin-mediated glucose
uptake via the phosphatidylinositol 3-kinsase (PI3K)/Akt
pathway, which, in turn, upregulates glucose transporter 4
(GLUT4) in adipocytes and skeletal muscle, leading to increased
glucose levels. Curcumin supplementation improves glycemic
control and lipid metabolism, and reduces oxygen radical species
in PCOS patients. Curcumin is a diarylheptanoid derived from the
rhizome of the Curcuma longa plant, which functions as an
anti-inflammatory and antioxidant which is very important in the
treatment of PCOS.
Curcumin inhibits the development of colorectal
cancer via regulating the USP4/LAMP3 pathway
Naunyn-Schmiedeberg's Archives of Pharmacology | September 2023
In this study, we aimed to explore the effects of curcumin on
the progression of colorectal cancer and its underlying
mechanisms involved. Curcumin significantly accelerated cell
apoptosis, and inhibited cell proliferation and invasion in LoVo
and HCT-116 cells. LAMP3 was augmented in colorectal cancer
tissues and cells, and curcumin could reduce the expression of
LAMP3. Curcumin decreased LAMP3 expression to exhibit the
inhibition role in the progression of colorectal cancer.
Curcumin downregulated USP4 to impeded the progression of
colorectal cancer via repressing LAMP3 expression. In addition,
curcumin obviously restrained tumor growth in mice through
downregulating USP4 and LAMP3 expression. These data indicated
that curcumin exert the anti-tumor effects on the development of
colorectal cancer through modulating the USP4/LAMP3 pathway.
This
spice treats indigestion just as well as prescription drugs
New York Post | September 2023 Turmeric is derived from the
root of the Curcuma longa plant, a type of ginger. The root
contains curcumin, a compound known to have anti-inflammatory
and antimicrobial properties. It’s long been used as an herbal
remedy throughout Asia, but there have never been any
head-to-head studies comparing turmeric to a prescription drug
for indigestion — until now. Researchers from Thailand’s
Chulalongkorn University enrolled 151 people with recurring
indigestion (functional dyspepsia) in a study comparing the
curcumin found in turmeric to omeprazole, commonly known as
Prilosec. “Oral curcumin was found to be safe and well tolerated.
Patients with functional dyspepsia treated with curcumin,
omeprazole and curcumin plus omeprazole had similar significant
symptomatic improvement,” the study authors wrote. There is a
large growing body of medical evidence pointing to the health
benefits of turmeric and curcumin, many of which are based on
the spice’s anti-inflammatory and antioxidant properties. In a
study of people with ulcerative colitis (a type of inflammatory
bowel disease), those who took 2 grams of curcumin a day along
with prescription drugs were more likely to have their symptoms
stay in remission than people who took the drugs alone. It may
also lower the risk of heart disease, according to the Cleveland
Clinic: Among healthy adults who took curcumin supplements for
12 weeks, resistance artery endothelial production — which is
linked to high blood pressure — was improved. Some research also
suggests that curcumin may protect those at risk for heart
disease by lowering certain levels of cholesterol. And among
people who had coronary artery bypass surgery, those who took 4
grams of curcumin a day had a 65% lower risk of having a heart
attack. And if that isn’t enough, there are numerous studies
that find turmeric and curcumin can play a role in fighting
depression, preventing cancer, improving memory and lessening
the pain from arthritis and other conditions.As more research is
done on the health benefits of turmeric and curcumin, the spice
may move into mainstream medicine. As the authors of the
indigestion study wrote, “the new findings from our study may
justify considering curcumin in clinical practice.”
Long-term oral administration of curcumin is
effective in preventing short-term memory deterioration and
prolonging lifespan in a mouse model of Alzheimer’s disease
Advances in Traditional Medicine | September 2023 Curcumin
has been shown to have the potential to ameliorate or prevent
the development of Alzheimer's disease. Survival rate was 34% in
the Alzheimer's disease control group, 100% in the 0.02%
curcumin, and 83% in the 0.5% curcumin group, significantly
longer in the curcumin groups than the Alzheimer's disease
control group. This study demonstrates that long-term intake of
low concentrations of curcumin may act on the
tau-phosphorylation, suppress brain inflammation, delay the
onset of Alzheimer's disease, and prolong the lifespan of the
mouse.
Turmeric may be as good for treating indigestion as
drug to curb excess stomach acid British
Medical Journal | September 2023 Turmeric is derived from the
root of the Curcuma longa plant. It contains a naturally active
compound called curcumin thought to have anti-inflammatory and
antimicrobial properties, and has long been used as a medicinal
remedy, including for the treatment of indigestion. SODA scores
indicated significant reductions in symptom severity by day 28
for pain (−4.83, –5.46 and −6.22) and other symptoms (−2.22,
–2.32, and −2.31) for those in the combined, curcumin alone, and
omeprazole alone groups, respectively. These improvements were
even stronger after 56 days for pain (−7.19, –8.07 and −8.85,
respectively) and other symptoms (−4.09, –4.12 and −3.71,
respectively). SODA also captures satisfaction scores: these
scarcely changed over time among the curcumin users, which might
possibly be related to its taste and/or smell, suggest the
researchers. No serious side effects were reported, although
liver function tests indicated some level of deterioration among
curcumin users carrying excess weight, note the researchers.
They acknowledge the small size of the study, as well as several
other limitations, including the short intervention period and
lack of long-term monitoring data. Further larger, long term
studies are needed, they say. Nevertheless, they conclude: “This
multicentre randomised controlled trial provides highly reliable
evidence for the treatment of functional dyspepsia,” adding that
"the new findings from our study may justify considering
curcumin in clinical practice."
Curcumin extends the lifespan of aging postmitotic
cells with mitochondrial dysfunction
bioRxiv Cold Spring Harbor Laboratory | September 2023
Curcumin, a natural compound, is explored for its anti-aging
potential. This study explores the influence of curcumin on the
postmitotic cellular lifespan (PoMiCL) of yeast during
chronological aging, examining its potential implications for
age-related diseases. Our findings reveal that curcumin
significantly extends the lifespan of postmitotic wildtype yeast
cells, with maximal effects observed at lower concentrations,
displaying a hormetic response. Importantly, curcumin mitigates
accelerated aging in cells afflicted by mitochondrial
dysfunction. These findings shed light on curcumin’s potential
as an anti-aging modulator and its relevance to age-related
diseases, offering insights into novel therapeutic approaches
for healthy aging while highlighting the context-dependent
nature of its effects. Recent research has drawn attention
to the potential impact of curcumin, a polyphenolic bioactive
compound derived from the rhizome of Curcuma longa (turmeric),
for its therapeutic potential across a wide spectrum of diseases
including mitigating the effects aging and increasing lifespan.
Two groundbreaking observational cohort studies conducted among
middle-aged and older Asian adults living in Singapore have
revealed an intriguing connection between the consumption of
curcumin-rich foods and healthspan. This study represents the
inaugural longitudinal exploration of the cognitive advantages
linked to curcumin obtained from natural dietary sources in
human subjects. The results emphasize the potential health and
longevity-enhancing effects of curcumin in the diet from natural
sources, providing valuable insights into how consuming curry
may affect various health aspects, including cognitive benefits
over time and the potential to extend the lifespan of patients
with cardio-metabolic and vascular diseases. Our results
demonstrate that curcumin has a significant impact on extending
the lifespan of postmitotic cells during chronological aging.
These findings align with previous studies that have highlighted
the beneficial effects of curcumin on healthspan and cellular
longevity. Notably, curcumin’s anti-aging effects exhibit a
biphasic dose-response pattern, with lower concentrations
showing greater efficacy. This hormetic effect of curcumin on
cellular lifespan, observed both in yeast and human cells, adds
an intriguing dimension to its potential as an anti-aging
intervention. In summary, our study provides valuable insights
into the intricate relationship between curcumin, postmitotic
cellular aging, and mitochondrial function. It demonstrates that
curcumin has the potential to extend the lifespan of postmitotic
cells, with its effectiveness influenced by concentration and
the presence of mitochondrial dysfunction. These findings
contribute to our understanding of curcumin’s role as a
potential modulator of cellular aging and emphasize the
importance of considering dosage and cellular context when
exploring its therapeutic applications. While this research
represents a significant step forward, further investigations
are needed to elucidate the precise molecular mechanisms
underlying curcumin’s effects on cellular lifespan and to
translate these findings into potential therapeutic
interventions for human aging and age-related diseases.
Curcumin and proton pump inhibitors for functional
dyspepsia: a randomised, double blind controlled trial
BMJ Evidence-Based Medicine | September 2023 Curcumin and
omeprazole had comparable efficacy for functional dyspepsia with
no obvious synergistic effect. Turmeric, scientifically known as
Curcuma longa L., has a long history of extensive use. This
plant has a valuable active compound, curcumin, which is used
both topically and orally for medicinal purposes. While curcumin
is commonly found in nourishing creams and cosmetics, it is also
available in the form of powder capsules used for treating
various gastrointestinal problems, including dyspepsia. Recent
findings from a Cochrane review suggested that curcumin may
offer moderate improvement in dyspepsia symptoms compared with
placebo. Curcumin, extracted from turmeric, is a hydrophobic
polyphenol with a low molecular weight. This compound exhibits a
broad range of biological properties, such as anti-inflammatory,
anti- oxidant, antiproliferative and antimicrobial properties.
Several clinical trials have established the pharmacological
properties of curcumin. Curcumin is effective in the treatment
of gastric ulcers, erosions and dyspepsia, with ulcers and
erosions reduced or even eradicated after administration of
curcumin (3000 mg/day) for up to 12 weeks, while abdominal pain
and discomfort were significantly reduced. Similarly to the
findings of the current study, curcumin has been shown to be
safe in numerous human studies, with only minor toxicity
associated with this polyphenol. Therefore, curcumin is
increasingly being viewed as a biomolecule capable of being
administered for an extended period without causing adverse
effects. The findings of the current study indicate that there
were no significant adverse events associated with the short
term use of PPI and curcumin. This study represents the first
head-to- head comparison demonstrating the efficacy of curcumin
in treating functional dyspepsia compared with omeprazole.
Curcumin was effective in all subtypes of functional dyspepsia.
Curcumin and omeprazole were both effective for functional
dyspepsia.
Safety and Efficacy of Turmeric (Curcuma longa)
Extract and Curcumin Supplements in
Musculoskeletal Health: A Systematic Review and Meta-Analysis
Alternative Therapies In Health And Medicine | September 2023
Curcuma longa is a rhizomatous, herbaceous, perennial herb
belonging to the ginger family and has a broad variety of
biological properties, such as antioxidant, anti- inflammatory,
antimutagenic, antimicrobial, and anticancer properties. 4,5
These properties belong to the bioactive principles in the
rhizomes, the hydrophobic polyphenols called curcuminoids, which
comprise curcumin, demethoxycurcumin, and bisdemethoxycurcumin,
of which curcumin—1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-
heptadiene-3,5-dione—is the major natural polyphenol.
Curcuminoids, commonly called curcumin, have been shown to
exhibit a broad spectrum of pharmacological actions proven in
several in-vitro and in-vivo studies as well as in clinical
trials. Curcumin has also been recognized as safe by the US Food
and Drug Administration (FDA). The effects of curcumin on joint
health and these disorders have been evaluated in several
clinical trials pertaining to its potent anti-inflammatory
action. The current meta-analysis has demonstrated the
effectiveness of curcumin in improving joint health. Several
studies have reported that curcumin is safe and effective for
various joint health conditions, such as joint pain,
osteoarthritis and rheumatoid arthritis.
Turmeric
might help treat your indigestion, study shows
CNN | September 2023 “In addition to anti-inflammatory
and antioxidant purposes, curcumin/turmeric could be an option
for treating dyspepsia with comparable efficacy to omeprazole,”
said lead study author Dr. Krit Pongpirul, associate professor
in the department of preventive and social medicine at
Chulalongkorn University in Bangkok. It makes sense that
research would investigate turmeric’s impact on indigestion,
because its compound curcumin has been studied in a wide variety
of inflammatory conditions, including inflammatory bowel disease
and arthritis, said Dr. Yuying Luo, a gastroenterologist and
assistant professor of gastroenterology at the Icahn School of
Medicine at Mount Sinai in New York City. Some studies have
shown that curcumin was helpful in conjunction with other
medications, she added.
Cytotoxicity of curcumin against CD44± prostate
cancer cells Avicenna Journal of
Phytomedicine | September 2023 Our findings indicate that
curcumin, by promoting the expression of tumor suppressors,
miR-383-5p and miR-708-5p, and inhibiting their target genes,
induced its cytotoxicity against CD44± PC cells. We trust that
curcumin could be established as a promising adjuvant therapy to
current prostate cancer treatment options following more
research in clinical settings. Curcumin is a phytochemical
product whose anti-prostate cancer effects on the inhibition of
proliferation, invasion, cellular adhesion, and angiogenesis of
many tumors have been confirmed (Termini et al., 2020). Multiple
studies have shown that curcumin and its analogs have promising
potential to target CSCs (Li and Zhang, 2014; Ramasamy et al.,
2015). Altogether, our study revealed that curcumin suppressed
cellular proliferation and induced apoptosis in CD44+ and CD44-
PC cells. We also showed that curcumin, by promoting the
expression of miR-383 and miR-708 and inhibiting their target
genes, induced its cytotoxicity against CD44± PC cells.
Considering that traditional cancer chemotherapeutic agents and
radiotherapy cannot eradicate CSCs, the cytotoxicity of curcumin
against CD44+ human prostate CSCs is a remarkable feature. We
trust that curcumin could be established as a promising adjuvant
to current PC treatment options following research in clinical
settings.
Turmeric could be as effective as medicine for
indigestion, says study The Guardian |
September 2023 Turmeric contains a naturally active compound
called curcumin, thought to have anti-inflammatory and
antimicrobial properties. It has long been used as a medicinal
remedy, including for the treatment of indigestion, in
south-east Asia.Researchers found that oral curcumin was safe
and well tolerated, and that patients in all three groups
experienced a similar improvement in symptoms. “This multi-centre
randomised controlled trial provides highly reliable evidence
for the treatment of functional dyspepsia,” adding that “the new
findings from our study may justify considering curcumin in
clinical practice”.
Curcumin: recent updates on gastrointestinal cancers
CyTA - Journal of Food | September 2023 Curcumin shows
multispectral anticancer effects and recent studies have
explored its mechanism of action to design and develop
anticancer therapies. In gastrointestinal cancer cells, curcumin
has been shown to induce cell death through apoptosis and to
cause cell cycle arrest. Additionally, curcumin prevents DNA
from replication during the S phase. It has been reported that
tumors can be reduced at different stages of the cell cycle
using curcumin. It blocks various enzymes that participate in
the growth and development of tumors and may resist tumor
treatment. Furthermore, curcumin also modulates cellular
progressions, i.e., protein kinase C activity, EGF (epidermal
growth factor) receptor intrinsic kinase activity, nuclear
factor kappa (NF-kB) activity, nitric oxide synthesize activity,
and suppresses lipid peroxidation (Imran et al., Citation2018).
Curcumin, a plant-derived polyphenol, has been identified as a
therapeutically effective food that exhibits pleiotropic
pharmacological effects on a variety of malignancies (Lim,
2022). Curcumin has an anti-tumor role in gastric cancer cells
via inhibiting invasion and proliferation and inducing apoptotic
cell death in experimental subjects (Kwiecien et al., 2019).
Curcumin has been chosen by the National Cancer Institute as a
third-generation cancer chemo preventive drug (Abd El‐Hack et
al., 2021). In different in vivo and in vitro studies, curcumin
has exhibited anticancer effects involving mechanisms such as
reduction in the formation of liver tumors, suppression of
metastasis of primordial germ cell (PGC), CXCR4 expression, and
inhibition of stromal cell-derived factor-1/CXCR4 signaling (Gu
et al., 2019). Furthermore, curcumin suppresses the p-Akt
protein expression, increments in PTEN expression, and reduction
in miR-21 levels. It also shows suppression of STAT3
phosphorylation, blocked STAT3-mediated signaling, induction of
growth arrest, and apoptosis (Qiang et al., 2019). Curcumin has
the effects of reducing the dosage, resistance and side effects
of chemotherapy drugs, besides a pivotal role in the modulation
of biological processes resulting in the prevention of cancer
particularly due to its radical scavenging activities and other
mechanisms (Zhou et al., Citation2011, Citation2017). Curcumin
possesses anticancer effects against different human
gastrointestinal cancer cell lines through various mechanisms.
It suppresses the cell proliferation, invasion and propagation
stages in different human cancer cell lines. Furthermore, its
sole and co-administration exhibit different effects on cancer
cells that make it an important compound to be used as a
therapeutic agent in different nutraceutical and pharmaceutical
formulations. In the near future, curcumin is anticipated to be
proven as a novel drug to cure and treat several human
gastrointestinal cancer cell lines.
A spice that gives curries its vibrant colour could
be a cure for indigestion, research suggests
Daily Mail | September 2023 The spice that gives curry its
yellow colour could be an unlikely cure for indigestion,
research suggests. Scientists have discovered that turmeric – a
common spice that many have in their kitchen cupboards – is as
effective as a drug for treating symptoms. The golden-orange
spice is derived from the root of the Curcuma longa plant and
contains a naturally active compound called curcumin. This is
thought to have anti-inflammatory and antimicrobial properties
and has long been used as a medicinal remedy in South East Asia.
‘In th trial, oral curcumin was found to be safe and well
tolerated. Patients with functional dyspepsia treated with
curcumin, omeprazole and curcumin plus omeprazole had similar
significant symptomatic improvement.’ Turmeric is also believed
to help fight off infection, protect against allergies, boost
memory and lift our mood.
Curcumin protects from LPS-induced activation in the
pathogenesis of neurological diseases and inflammatory responses
NueroReport | September 2023 Our data demonstrated that
curcumin significantly increased the level of phosphorylated
AMPK protein in LPS-activated astrocytes. In addition, our data
demonstrated that curcumin play an inhibitory role on the
migration, autophagy, the pro-inflammatory mediators by the AMPK
signaling pathway in LPS-activated astrocytes. These results
might contribute to a promising therapeutic intervention in the
neurological diseases-related astrocytes activation. Curcumin ,
as a phenolic pigment extracted from curcuma longa, has been
shown to suppress inflammatory response and anti-oxidant against
the pathological changes in various neurological disorders. It
is reported that curcumin could inhibit the inflammatory
cytokines such as TNF-α, IL-1β, IL-6, and monocyte
chemoattractant protein 1 (MCP-1). Additionally, curcumin exerts
the anti-oxidant effect through nuclear factor erythroid
2-related factor 2 (Nrf2) pathways. Recent studies have revealed
that curcumin acts as direct inhibition of astrocyte activity in
neurodegenerative diseases and ischemic stroke. In summary, we
provided evidence showing that curcumin markedly inhibited the
proliferation of in LPS-activated astrocytes. Our results
demonstrated that the inhibiting effects of the curcumin on
migration, autophagy, the production of pro-inflammatory
mediators, and the oxidative stress were mediated at least by
the AMPK signaling pathway. Therefore, curcumin, a potent
anti-oxidant, could be beneficial for ameliorating the
neurological diseases-related astrocytes activation. What is
more, our findings may provide a new molecular mechanism for the
therapeutic effects of curcumin.
Turmeric May Fight Indigestion as Well as Some
Medications, Study Finds Prevention |
September 2023 New research finds curcumin, the active
compound in turmeric, was just as effective as common
over-the-counter medications at treating indigestion.Researchers
found no significant differences in the indigestion symptoms of
people taking omeprazole, curcumin, or the combination of the
two. (Those symptoms can include pain, a burning feeling, or
discomfort in the upper abdomen, feeling uncomfortably full
after a meal, or feeling full too soon while eating, per the
National Institute of Diabetes and Digestive and Kidney
Diseases, NIDDK). The researchers concluded that curcumin and
omeprazole had “comparable efficacy” for chronic
indigestion—meaning, they both worked about the same. The idea
of using turmeric or curcumin for indigestion isn’t totally out
there: Turmeric has been used in parts of Southeast Asia to
treat stomach discomfort for years, says study co-author Krit
Pongpirul, M.D., M.P.H., Ph.D., associate professor at
Chulalongkorn University and an adjunct faculty member at the
Johns Hopkins Bloomberg School of Public Health.Scientific
research into curcumin for indigestion is still ongoing, but the
compound may help tamp down acid production in the stomach, says
Rudolph Bedford, M.D., a gastroenterologist at Providence Saint
John’s Health Center in Santa Monica, CA. “Some people also use
curcumin to treat pain that may be due to inflammation of some
type,” he points out, noting that it’s possible the compound
could help stomach pain from indigestion as well.
An
Overview of the Enhanced Effects of Curcumin and
Chemotherapeutic Agents in Combined Cancer Treatments
International Journal of Molecular Sciences |
August 2023 Curcumin, a polyphenol, has been shown to have
extensive cytotoxic functions against cancer cells, including
combined treatment. In particular, we have described the results
of recent preclinical and clinical studies exploring the
pleiotropic effects of curcumin in combination with standard
drugs and the potential to consider it as a promising new tool
for cancer therapy. Curcumin, a yellow pigment of the spice
turmeric Curcuma longa Linn, is one of the most studied
phytochemicals used as anticancer molecules. This polyphenol has
been used in traditional medicine in Asia since ancient times
and it has been shown to have extensive cytotoxic effects
against cancer cells. In addition, curcumin has also shown
beneficial and protective functions in acute myocardial
infarction and cardiovascular diseases, chronic atherosclerosis,
neurodegenerative diseases and autoimmune diseases. Interest in
curcumin has gradually increased after several studies
demonstrated its chemotherapeutic and chemopreventive effects.
Several studies have reported that curcumin is able to affect
gene expression and trigger various signalling mediators such as
NF-κB, COX-2, AP-1, EGFR, MMP9 and PKC, which are involved in
several signalling pathways such as angiogenesis, survival,
metastasis and proliferation. Curcumin has been reported to
exert significant immunomodulatory activity and protect the
immune system from cancer-related suppression. Since curcumin is
able to modulate gene expression, in vitro studies have been
conducted to investigate transcriptional modulation associated
with the use of this phytochemical. Transcriptomic analyses
performed after curcumin treatment in various cancer cells
showed specific modulation of gene expression. Further analysis
of microRNA expression showed that curcumin can also modulate
various non-coding genes in different cellular contexts in human
pancreatic cancer or in non-small cell lung cancer. In
addition, other studies have shown that curcumin can influence
the epigenomic landscape, as it is able to induce specific
methylation changes that are not determined by a direct effect
on DNA methyltransferases but are a consequence of curcumin’s
direct effect on modulating gene expression. As for the
cytotoxic effects of curcumin in cancer, this ability is closely
linked to the modulation of signalling pathways related to
cancer, such as cell cycle, apoptosis, and resistance to
multiple drugs. For example, curcumin has been reported to
prevent colon cancer proliferation by blocking the cell cycle
and accelerating apoptosis. In human colon cancer cells,
curcumin significantly inhibited cell growth. It also triggered
apoptosis via a mitochondria-mediated pathway. Curcumin induced
the release of cytochrome c, significantly increased BAX and
p53, and showed a marked reduction in BCL-2 and survivin in
colorectal carcinoma LoVo cells. Moreover, curcumin was reported
to significantly decrease the expression of cyclin D and inhibit
the activity of p21-activated kinase1 (PAK1), leading to the
suppression of gastric cancer cell proliferation and invasion.
Curcumin as a functional food in cancer
Molecular Mechanisms of Action of Functional Foods and
Nutraceuticals for Chronic Diseases | August 2023 The
correlation between various plant consumption and reduced cancer
development has been well-established in many epidemiological
studies. Among these, turmeric (Curcuma longa), or the
“golden spice”, is a famous ingredient within the Indian
sub-continent cooking and Ayurveda holistic medicine approach.
The bioactive form of turmeric known as curcumin has been
studied extensively in vitro and in vivo using a wide range of
cancer types. Almost all studies confirmed not only remarkable
anti-cancer activities but also selectivity and safety towards
normal cells. The anti-cancer properties of curcumin were
evident from the early stages of cancer initiation and remain
effective even within highly aggressive metastatic cancer
models. Such impacts were attributed to multi-targeted
mechanisms of curcumin involving direct and indirect methods,
signaling pathways, and molecular and biochemical targets.
Effects of curcumin on blood pressure: A systematic
review and dose-response meta-analysis
Nutrition, Metabolism & Cardiovascular Diseases | August 2023
Curcumin has numerous biological activities and pharmacological
effects, including anti-inflammatory, antioxidant, capabilities,
and hepatoprotective effects. Subgroup analysis revealed a
significant reduction only in DBP levels (WMD: -0.76 mmHg, 95%
CI: -1.46,-0.05; P=0.03). Also, a significant reduction in SBP
(WMD: -1.55 mmHg, 95% CI: -2.85, -0.25; P = 0.01) and DBP (WMD:
-1.73 mmHg, 95% CI:-2.67, -0.79; P<0.01) was noticed by curcumin
supplementation in studies that performed on women. The current
study suggests that consuming curcumin may improve blood
pressure when
administered in long durations ≥ 12 weeks.
Combination of epigallocatechin 3 gallate and
curcumin improves d-galactose and normal-aging associated memory
impairment in mice Scientific Reports
| August 2023 Curcumin improves aging-associated memory
impairment in d-galactose (D-gal) and normal-aged mice. Curcumin
and Epigallocatechin 3 gallate (EGCG) combination substantially
reduced the oxidative stress that commonly mediates aging. The
co-administration of EGCG and curcumin significantly increased
retention time and remarkably ameliorated the levels of
glutathione, superoxide dismutase, catalase, advanced oxidation
protein products, nitric oxide, and lipid peroxidation compared
to the monotherapy of EGCG or curcumin in mice hippocampi. The
behavioral and biochemical studies revealed that the combination
of EGCG and curcumin showed better improvement in rescuing
aging-associated memory disorders in mice. EGCG and curcumin
combination could serve as a better choice in managing
aging-related memory disorders. improvements in behavioral
endophenotype appear due to the antioxidant, anti-inflammatory,
and anti-senescence properties of curcumin, shown in a previous
study. Curcumin produces neuroprotective effects by exerting
antioxidant, anti-aging, and anti-neuroinflammation properties.
A study showed that curcumin protects memory from impairment in
D-gal and NA-induced memory impairment by regulating
degeneration, proliferation, and senescence of neuronal cells.
Additionally, curcumin was found to improve cognitive
dysfunction by increasing synaptic density in the AD animal.
We investigated the beneficial effects of EGCG and curcumin on
oxidative stress in the two robust aging mice models by
performing behavioral and biochemical studies. A combination of
EGCG with curcumin exhibits greater protection from
aging-related memory impairment by modulating oxidative stress
biomarkers.
The beneficial effects of curcumin supplementation
on blood lipid levels among patients with metabolic related
diseases in Asia area: a systematic review and meta-analysis of
randomized controlled trials
Frontiers in Sustainable Food Systems | August
2023 Numerous studies have shown that curcumin has a variety
of pharmacological activities, including antibacterial,
antitumour, anti-inflammatory, antioxidant, anticoagulant, and
is particularly prominent in improving metabolic diseases (Asai
and Miyazawa, 2001; Ejaz et al., 2009). Curcumin has been
reported to promote weight loss, improve hyperlipidaemia, and
reduce hepatic steatosis (Menon and Sudheer, 2007; Ak and Gülçin,
2008). In addition, curcumin has been shown to have therapeutic
effects on various diabetic complications such as nephropathy
and cardiovascular disease in patients with type 2 diabetes (Jeenger
et al., 2015). A meta-analysis showed that curcumin
supplementation also significantly reduced levels of
inflammatory markers and biomarkers of oxidative stress in
patients with Mets (Sun et al., 2022). Second, the potential
mechanisms by which curcumin improves obesity and lowers blood
lipids have received increasing attention. For example, curcumin
blocks preadipocyte differentiation in vitro (Sakuma et al.,
2017) and inhibits the expression of inflammatory cytokines in
TNFα-stimulated adipocytes (Gonzales and Orlando, 2008).
Curcumin also inhibits 3T3-L1 adipocyte differentiation and
promotes preadipocyte apoptosis (Wu et al., 2019). Curcumin
supplementation significantly reduced triglycerides, total
cholesterol and low-density lipoprotein cholesterol but no
effect on HDL. In the non-linear dose-response analysis, we
observed a significant effect of curcumin supplementation dose
on triglycerides levels (P-non-linearity = 0.022). In
conclusion, curcumin may be beneficial in reducing
triglycerides, total cholesterol and low-density lipoprotein
cholesterol levels in the Asian populations with metabolic
diseases. The dose of curcumin intervention may be an underlying
factor influencing levels. The results of this meta-analysis may
be useful in making recommendations for the use of curcumin as a
dietary supplement.
A
review on curcumin colon-targeted oral drug delivery systems for
the treatment of inflammatory bowel disease
Inflammopharmacology | August 2023 The use curcumin
is one such treatment option that has seen an increase in usage
in treating inflammatory bowel disease. Curcumin is derived from
a rhizome of turmeric (Curcuma longa), and the results of
studies on the use of curcumin to treat inflammatory bowel
disease are promising. These studies suggest that curcumin
interacts with cellular targets such as NF-κB, JAKs/STATs,
MAPKs, TNF-α, IL-6, PPAR, and TRPV1 and may reduce the
progression of inflammatory bowel disease. Potentially, curcumin
can be used as a therapeutic agent for patients with
inflammatory bowel disease when it reduces the incidence of
clinical relapse.
AATF-mediated Liver Damage and Inflammation to
Cancer: Therapeutic Intervention by Curcumin in Experimental
MASH-HCC JSS Medical College | August 2023
Curcumin treatment suppressed hepatic expression of
inflammatory, fibrogenic, and oncogenic markers. Of note, there
was a significant reduction in the expression of AATF upon
curcumin treatment in WDSW/CCl4 mice and human HCC cells. In
contrast, curcumin upregulated Kruppel-like factor 4 (KLF4) in
MASH liver and HCC cells, which is known to downregulate sp1
(specificity protein-1) expression. Thus, curcumin treatment
effectively inhibited the progression of MASH to HCC by
downregulating the expression of AATF via the KLF4-Sp1 signaling
pathway. Curcumin, an active component of curcuminoids derived
from the rhizome of turmeric (Curcuma longa, Zingiberaceae), is
a diarylheptane and is known for its anti-inflammatory,
antioxidant, and anti-cancer properties. Curcumin is known to
mediate anticancer effects by modulating inflammatory cytokines,
growth factors, transcription factors, and multiple signaling
proteins. Several studies have shown the positive effects of
curcumin on ameliorating MASH. Curcumin lowers de novo
lipogenesis by reducing the levels of sterol regulatory element
binding protein 1-c (SREBP-1c) and adipose
differentiation-related protein (ADRP). In the streptozotocin
(STZ)-induced MASH-HCC model, curcumin protected liver damage
from ER stress and related inflammation. Studies have suggested
that curcumin may help reduce liver inflammation and oxidative
stress, which are key factors in the development and progression
of MASH. Additionally, curcumin has been found to have
beneficial effects on lipid metabolism, insulin resistance, gut
microbiota, and fibrosis. In conclusion, the current study adds
to the growing body of evidence supporting the promising role of
curcumin and its potential applications in the prevention and
treatment of MASH-HCC. We demonstrated that curcumin ameliorates
AATF- mediated liver damage and inflammation to cancer in
MASH-HCC via KLF4 and Sp1 signaling pathway. Furthermore, the
study offers valuable insight into the potential benefits of
curcumin for MASH-HCC, for which the development of effective
therapeutic agents is an absolute necessity.
A Review on the Golden Plant Turmeric and Its
Bioactive Compound Curcumin Biosynthesis of
Bioactive Compounds in Medicinal and Aromatic Plants | August
2023 Bioactive compounds like curcumin, identified in
turmeric, are rich in therapeutics. In the last 10 years,
research interests have concentrated on bioactive curcuminoid
compounds (curcumin, demethoxy curcumin, and bisdemethoxy
curcumin). In recent studies, curcumin has been found to
play a very effective role against cancer, biotic, inflammatory,
and aging. The present study summarizes the pharmaceutical
usages of turmeric with distinct reference to its polyphenolic
compound curcumin.
Curcumin derived from medicinal homologous foods:
its main signals in immunoregulation of oxidative stress,
inflammation, and apoptosis Frontiers in
Pharmacology | August 2023 Curcumin, the primary component
derived from medicinal homologous foods like curcuma longa
rhizome, is reported to play vital actions in organic
activities, such as the numerous pharmacological functions
including anti-oxidative stress, anti-inflammation and
anti/pro-apoptosis in treating various diseases. Due to its role
in oxidative stress, inflammatory response, and apoptosis,
curcumin shows significant pharmacological potential and has
exhibited favorable effects concerning various metabolic
disorders, immune-related diseases, and cancers. Growing
experimental evidence revealed that curcumin had been shown to
scavenge ROS, inhibit the production of pro-inflammatory
cytokines, and modulate various signaling pathways involved in
apoptosis. Furthermore, curcumin exhibits an excellent safety
profile, with no significant adverse effects reported even at
high doses. Curcumin, a bioactive compound present in turmeric,
has emerged as a potential health-promoting agent in the
regulation of various diseases. This mini-review offers a
comprehensive summary of recent advances in elucidating the
preventive and curative effects of curcumin on oxidative stress,
inflammation, and apoptosis in non-cancerous diseases and
cancers. Generally, curcumin exhibits its antioxidant property
through AMPK/Nrf2/ARE/Keap1 pathway activation, its
anti-inflammatory property via NF-κB/AP-1/MAPK pathways
inhibition, and its anti-apoptosis property by blocking JAK/STAT
and ER stress-induced pathways while activating PI3K/AKT/mTOR
pathways in non-cancerous diseases. Conversely, curcumin
demonstrates pro-oxidant, anti-inflammatory, and pro-apoptosis
properties in cancers.
Lysosomes, curcumin, and anti-tumor effects: how are
they linked? Frontiers in Pharmacology |
August 2023 Curcumin is a natural active ingredient from
traditional Chinese medicine (TCM) that has multi-target
characteristics to exert extensive pharmacological activities
and thus has been applied in the treatment of various diseases
such as cancer, cardiovascular diseases, nervous system, and
autoimmune disorders. Curcumin, an orange-yellow polyphenolic
compound originating from TCM, has attracted much attention
owing to its anti-inflammatory, anti-bacterial, anti-oxidant,
and other biological activities. Many studies have focused on
the anti-tumor activity of curcumin. It has been illustrated
that curcumin can exert an anti-tumor effect by modulating
growth factors, enzymes, transcription factors, kinases,
inflammatory cytokines, and pro- and anti-apoptotic proteins.
Curcumin has anti-inflammatory, anti-diabetic, anti-tumor and
anti-aging therapeutic potential and is widely used in various
diseases such as cancer, cardiovascular disease, neurological
and autoimmune (Raghav et al., 2021). The anti-tumor mechanisms
of curcumin are diverse, but recent studies have shown that
curcumin and its related derivatives can regulate their
biological functions by targeting the lysosomal pathway, thereby
exerting anti-tumor effects. Curcumin can mediate lysosomes to
regulate cellular energy metabolism and lysosome biogenesis,
inhibit tumor cell proliferation or promote tumor cell
apoptosis, and play an anti-tumor effect. Lysosome itself or
various CTS secreted by it can also enhance tumor invasion and
metastasis by promoting tumor EMT or tumor angiogenesis, while
curcumin can inhibit the above processes. In addition, curcumin
can also reverse the MDR mediated by lysosomes and improve the
anti-tumor effect of chemotherapy drugs. Finally, curcumin has a
positive immunomodulatory effect on the body by regulating
lysosome-induced immune dysfunction and immune checkpoint
inhibition.
The Beneficial Effects of Curcumin on Lipids: Possible
Effects on Dyslipidemia-Induced Cardiovascular Complications
Current Medicinal Chemistry | August 2023 Recent evidence
suggest that curcumin may improve lipid metabolism and prevent
dyslipidemia-induced cardiovascular complications via several
pathways. Although the exact molecular mechanisms involved are
not well understood, the evidence presented in this review
suggests that curcumin can provide significant lipid benefits
via modulation of adipogenesis and lipolysis, and prevention or
reduction of lipid peroxidation and lipotoxicity via different
molecular pathways. Curcumin can also improve the lipid profile
and reduce dyslipidemia-dependent cardiovascular problems by
impacting important mechanisms of fatty acid oxidation, lipid
absorption, and cholesterol metabolism.
Curcumin inhibits esophageal squamous cell carcinoma
progression through down-regulating the circNRIP1/miR-532-3p/AKT
pathway Environmental toxicology | August
2023 Curcumin shows an anti-cancer role in many kinds of
tumors. Curcumin could time- and dose-dependently inhibit
esophageal squamous cell carcinoma cells activity. Additionally,
ESCC cells exposed to 20 μM of curcumin exhibited significantly
decreased proliferative and invasive capacities, as well as
enhanced cell apoptosis. Exposure to 10–20 μM of curcumin
inhibited circNRIP1 expression. Curcumin inhibited AKT
phosphorylation by up-regulating miR-532-3p expression, thereby
inhibiting the activation of the AKT pathway. In summary,
curcumin is a potent inhibitor of esophageal squamous cell
carcinoma growth, which can be achieved through the regulation
of the circNRIP1/miR-532-3p/AKT pathway. This research may
provide new mechanisms for curcumin to inhibit the malignant
development of esophageal squamous cell carcinoma.
Male
and Female Breast Cancer and the Effect of Medicinal Plants
Medium.com | August 2023 Curcumin has
garnered significant interest from researchers due to its
potential anti-cancer properties. It targets multiple pathways
and prevents molecular deregulation, leading to reduced cancer
growth. In breast cancer, curcumin has demonstrated various
anti-cancer activities, suppressing tumor cell growth,
inhibiting cancer invasion, and impeding metastasis. It plays a
crucial role in promoting cancer cell death, minimizing
inflammation, and slowing down tumor growth. Curcumin’s
beneficial effects on breast cancer involve its action on
several signaling pathways. It suppresses the activity of MMP
(Matrix Metalloproteinase) genes, inhibits cell proliferation in
triple-negative breast cancer cells via the EGFR (Epidermal
Growth Factor Receptor) — MAPK (Mitogen-Activated Protein
Kinases) signaling pathway, and hinders cell migration and
invasion through the TGF-beta/Smad pathway and the Akt/SKP2
signaling pathway. Moreover, curcumin enhances sensitivity to
tamoxifen, a commonly used breast cancer treatment, and induces
apoptosis, or programmed cell death, in breast cancer cells.
Lastly, it has shown the ability to reduce metastatic activity
in estrogen receptor-negative breast cancer cells. Overall,
curcumin’s multifaceted actions make it a promising candidate
for further exploration as a potential therapeutic agent in
breast cancer treatment.
The effect of curcumin-piperine on cardiometabolic,
inflammatory and oxidative stress factors and macular vascular
density in optical coherence tomography angiography (OCTA) in
patients Avicenna Journal of Phytomedicine
| August 2023 Curcumin is a safe phytochemical with
antioxidant, anti-inflammatory, antidiabetic, and lipid-lowering
effects. Curcumin, the biologically active substance in
turmeric, is a low molecular weight hydrophobic flavonoid with
numerous health benefits including antioxidant and
anti-inflammatory activities (Jeenger et al., 2015; Neerati et
al., 2014; Mohajeri et al., 2020; Parsamanesh et al., 2018;
Farhood et al., 2019; Gorabi et al., 2019; Mortezaee et al.,
2019; Shakeri et al., 2019). No significant adverse effects are
associated with supplementation with curcumin, even at doses
above 8 g/day (Mirzaei et al., 2017). Many regulatory proteins,
including chemokines, interleukins, hematopoietic growth
factors, and transcription factors, are modulated by curcumin,
thus reducing the inflammatory process (Peddada et al., 2019).
In several studies, curcumin has been shown to downregulate
tumor necrosis factor (TNF) -α (Li et al., 2013) and C-reactive
protein (Adibian et al., 2019). Curcumin supplementation
improved glycemic factors, low-density lipoprotein, very
low-density lipoprotein, and triglycerides in patients with
diabetes (Neerati et al., 2014). It also significantly lowered
blood glucose levels (Nabavi et al., 2015) and modulated retinal
disorders in diabetic rats by preventing retinal thinning,
apoptosis of retinal ganglion cells and inner nuclear layer
cells, and thickening the retinal capillary basement membrane
(Yang et al., 2018). In obese mice, curcumin consumption
significantly improved glycemic status (blood glucose, glucose
tolerance, and, HbA1C) and insulin sensitivity (Weisberg et al.,
2008). The effectiveness of curcumin on diabetes has been
discussed in several recent meta-analyses. In a way that
curcumin improves blood sugar, and lipid factors, and reduce
insulin resistance, it has a beneficial effect on improving and
preventing the progression of diabetes (Altobelli et al., 2021;
Zhang et al., 2021; Poolsup et al., 2019).
Proposed
effect of curcumin in type I diabetes mellitus
Minia Journal of Medical Research | August 2023 People of all
ages may develop diabetes mellitus, a chronic condition caused
by insufficient insulin production and activity. The damaging
effect of STZ on the pancreatic beta cells resulted in T1DM and
protective effect of curcumin on beta cells that was evaluated
by assessment of glucose and insulin, in the diabetic rats
’serum.
Proteomic analysis of ITPR2 as a new therapeutic
target for curcumin protection against AFB1-induced pyroptosis
Ecotoxicology and Environmental Safety | July 2023 Curcumin
exhibits excellent anti-inflammatory, and anti-cancer properties
with few side effects. Curcumin has anti-oxidant,
anti-inflammatory and anti-cancer properties. (Jin et al., 2020,
Muhammad et al., 2018a). Modern research has discovered some
unknown properties of curcumin, including anti-mutagenic,
anti-cardiovascular disease and anti-microbial activities (Mahjoob
and Stochaj, 2021, Mahmood et al., 2015). Curcumin has fewer
side effects and plays an important role in the prevention and
treatment of various diseases. Research shows that curcumin
alleviates AFB1-induced liver injury by regulating Nrf2 pathway
and NLPR3 inflammasome (Wang et al., 2022). Our team found
curcumin can inhibit inflammatory response and oxidative stress
through up-regulating the expression of Nrf2 and GST, changing
long non coding RNA expression profiles, and inhibiting
TLR4/RIPK pathway to protect the broilers liver injury induced
by AFB1 (Li et al., 2021, Li et al., 2022, Muhammad et al.,
2018b, Wang et al., 2018). In this study, we established an
8-week model of curcumin alleviating AFB1 induced liver injury
in mice. Curcumin supplementation showed effective protection
against AFB1-induced liver injury. This is consistent with
earlier finding (Wang et al., 2022).
Antiviral Mechanisms of Curcumin and Its Derivatives
in Prevention and Treatment of COVID-19: A Review
Advances in Experimental Medicine and Biology | July 2023
Curcumin, as a food nutraceutical with anti-inflammatory and
antioxidant effects, is now under consideration for the
prevention and treatment of COVID-19. Curcumin has been
demonstrated to retard the entrance of SARS-CoV-2 into cells,
interfere with its proliferation inside cells, and curb the
hyperinflammatory state caused by the virus by modulating immune
system regulators, minimizing the cytokine storm effect, and
modulating the renin-angiotensin system.
Curcumin targets miR-134-5p to suppress the
progression of colorectal cancer through regulating the
CDCA3/CDK1 pathway Naunyn-Schmiedeberg's
Archives of Pharmacology | July 2023 Curcumin treatment
repressed cell growth and invasion, and induced cell apoptosis
in HCT-116 and SW620 cells. Curcumin elevated miR-134-5p
expression and restrained CDCA3 expression in HCT-116 and SW620
cells. MiR-134-5p inhibitor or CDCA3 overexpression could
restore the effects of curcumin on cell growth, apoptosis, and
invasion in HCT-116 and SW620 cells. MiR-134-5p targeted CDCA3,
and CDCA3 could rescue the repressive effects of miR-134-5p on
the progression of colorectal cancer. Moreover, CDCA3 interacted
with CDK1, and CDK1 overexpression blocked the suppressive
effects of CDCA3 downregulation on the development of colorectal
cancer. In addition, curcumin treatment repressed tumor growth
in colorectal cancer via increasing miR-134-5p and
downregulating CDCA3 and CDK1 expression in vivo. Our findings
provided the evidence that curcumin upregulated miR-134-5p to
inhibit the progression of colorectal cancer by regulating
CDCA3/CDK1 pathway.
Turmeric Could Aid in Recovery, Study Suggests. New
research highlights the anti-inflammatory benefits of the spice
Runner's World | July 2023 Dave Clayton, Ph.D., senior
lecturer in nutrition and exercise physiology at Nottingham
Trent University in the U.K. told Runner’s World that curcumin
is a polyphenol compound with antioxidant and anti-inflammatory
properties and has been shown to down-regulate various
inflammatory processes. “The reduction we saw at about 64 hours
post-match likely reflects a reduction in systematic
inflammation, indicating that turmeric supplementation has
attenuated exercise-induced inflammation,” he said. “Previous
studies have also found that curcumin has reduced delayed onset
muscle soreness after exercise, and we also saw that subjective
muscle soreness was reduced with turmeric supplementation.”
Curcumin
protects against the age-related hearing loss by attenuating
apoptosis and senescence via activating Nrf2 signaling in
cochlear hair cells Biochemical
Pharmacology | July 2023 Curcumin is a bioactive compound of
Curcuma longa with antioxidant properties. Curcumin, extracted
from the plant Curcuma longa, is a chemical monomer that can
cross the blood–brain barrier to treat diseases. Curcumin has
been shown to exhibit antioxidant, anti-inflammatory,
anticancer, antifungal, and antiviral activities, and thus has
the potential therapeutic effects on various malignant diseases
and chronic illnesses. In addition, curcumin has a protective
effect on degenerative diseases such as cardiomyocyte
senescence, Alzheimer's disease, and lumbar radiculopathy. In an
animal model of noise-induced hearing loss, curcumin prevented
apoptotic index within the cochlear supporting tissues and
lateral wall. We found that treatment with curcumin could
attenuate progressive hearing loss in C57BL/6J mice. The above
results indicate that it is of great significance to further
develop curcumin as a potential agent against age-related
hearing loss.
Does Curcumin Boost Testosterone Levels?
RealMuscle.co.uk | July 2023 Curcumin, the main active
component in turmeric powder, was found to significantly
increase the testosterone levels in male rats even when given in
moderate doses. This was reported by scientists at Redeemer's
University in Nigeria. The researchers investigated how gallic
acid and curcumin affected the testicles of rats. Astonishingly,
the curcumin group had testosterone levels that were 257% higher
than the control group, and the group that received both
compounds had testosterone levels that were 184% higher.
According to this study, curcumin increased testosterone
production and protected against the negative effects of gallic
acid. The increase in testosterone levels was attributed to an
increase in the activity of enzymes like 3-beta-HSD and
17-beta-HSD in the testicles. These enzymes play a crucial role
in producing testosterone. The researchers concluded that
curcumin could potentially be used as an alternative medication
to treat male fertility issues. Curcumin also has potential to
increase testosterone production.
Evaluation of Curcumin-Piperine Supplementation in COVID-19
Patients Admitted to the Intensive Care: A Double-Blind,
Randomized Controlled Trial Advances in
Experimental Medicine and Biology | July 2023 Curcumin is a
traditional remedy for diseases associated with
hyper-inflammatory responses and immune system impairment.
Piperine, a bioactive compound in black pepper, has the
potential to enhance curcumin bioavailability. This study aims
to examine the effect of the curcumin-piperine
co-supplementation in patients infected with SARS-CoV-2 and
admitted to the intensive care unit (ICU). After 1 week of the
intervention, serum aspartate aminotransferase (AST) (p = 0.02)
and C-reactive protein (CRP) (p = 0.03) were significantly
decreased, and hemoglobin was increased (p = 0.03) in the
curcumin-piperine compared to the placebo group. The study
results showed that short-term curcumin-piperine supplementation
significantly decreased CRP, AST, and increased hemoglobin in
COVID-19 patients admitted to the ICU. Based on these promising
findings, curcumin appears to be a complementary treatment
option for COVID-19 patients.
Meta-study confirms positive effects of curcumin
supplementation in rheumatoid arthritis
ergo-log.com | June 2023 Rheumatic patients respond well to
supplementation with curcumin. According to a Chinese
meta-study, curcumin reduces the inflammatory reactions that
play a central role in rheumatism. As a result, patients suffer
less from painful, tender and swollen joints. Curcumin
supplementation reduced pain and the number of times the
subjects experienced tender or swollen joints. The effect of
curcumin was not only subjective in nature, but also
demonstrable in medical analyses. For example, curcumin
supplementation reduced the concentration of rheumatoid factors
in the blood. Serious side effects did not occur.
Role
of Turmeric and Curcumin in Prevention and Treatment of Chronic
Diseases: Lessons Learned from Clinical Trials
ACS Pharmacology & Translational Science | June 2023
Turmeric (Curcuma longa) has been used for thousands of years
for the prevention and treatment of various chronic diseases.
Curcumin is just one of >200 ingredients in turmeric. Almost
7000 scientific papers on turmeric and almost 20,000 on curcumin
have been published in PubMed. A total of 148 references were
found to be relevant for the key term "turmeric and clinical
trials", of which 70 were common in both PubMed and Scopus, 44
were unique to PubMed, and 34 were unique to Scopus. Similarly,
for the search term "curcumin and clinical trials", 440
references were found to be relevant, of which 70 were unique to
PubMed, 110 were unique to Scopus, and 260 were common to both
databases. These studies show that the golden spice has enormous
health and medicinal benefits for humans.
Role
of the Dietary Phytochemical Curcumin in Targeting Cancer Cell
Signalling Pathways Plants | June 2023
Curcumin exhibits numerous biological effects, including
anti-inflammatory, cardioprotective, antidiabetic, and
anti-aging activities. It has also been extensively studied for
its role as a cancer chemopreventive and anticancer agent.
Curcumin has various health benefits, including
anti-inflammatory, anti-allergic, antioxidant, and anticancer
properties. The potential therapeutic effects of curcumin on
cancer continue to draw great interest from the scientific
community. The activity of curcumin on different types of
cancer, including breast cancer, chronic myeloid leukaemia, head
and neck squamous cell carcinoma, colorectal cancer, prostate
cancer, intestinal adenomas, and cervical cancer, has been
demonstrated in numerous in vitro, in vivo and clinical studies.
This effect is mediated via various pathways, including
PI3K/Akt, JAK/STAT, MAPK, Wnt/β-catenin, p53, NF-κB, and
apoptosis-related cell signalling. Curcumin has so far shown a
promising role in cancer chemoprevention and chemotherapy.
Effect of Curcumin Consumption on Inflammation and
Oxidative Stress in Patients on Hemodialysis: A Literature
Review Nutrients | June 2023 Regular
curcumin consumption has been shown to reduce inflammation and
oxidative stress in subjects with chronic pathologies,
suggesting that the daily intake of curcumin may alleviate these
conditions in HD patients. Curcumin is the main active
constituent of turmeric, and it is characterized by containing
phenolic groups which confer antioxidant and anti-inflammatory
effects. Curcumin supplementation in CKD patients on HD reduces
the expression of inflammatory markers such as NF-κB, C-reactive
protein and tumor necrosis factor-alpha (TNF-α). One of
the most promising bioactive compounds is curcumin, a major
polyphenol in turmeric that has been successfully evaluated in
the treatment of several chronic pathologies, including CKD.
Several mechanisms of action associated with the antioxidant
role of curcumin have been proposed as responsible for its
anti-inflammatory activity. This has been evidenced in
preclinical and clinical studies where regular intake of
variable doses of curcumin has been effective in controlling
oxidative and inflammatory parameters. Oral administration of
free curcumin together with adjuvants that decrease its hepatic
metabolism, such as piperine, has increased its bioavailability
in both rats and humans. This literature review analyzed the
available preclinical and clinical studies evaluating the
antioxidant and anti-inflammatory effects of curcumin and its
association with CKD. The background information gathered leads
to the conclusion that curcumin consumption can be successfully
integrated as a dietary therapeutic adjuvant in HD patients.
Curcumin suppressed the proliferation and apoptosis
of HPV-positive cervical cancer cells
Phytotherapy Research | June 2023 Curcumin, the active
ingredient of the turmeric plant, has been gaining attention
over the past two decades as an antioxidant, anti-inflammatory,
and anticancer agent. In the present study, the HPV-positive
cervical cancer cells HeLa and CaSki were treated with curcumin,
and the results showed that curcumin has a dose-dependent and
time-dependent inhibitory effect on cell viability. Furthermore,
the influence of different concentrations of curcumin on the
mitochondrial membrane potential was evaluated through JC-1
staining and found to dramatically decrease the membrane
potential in treated HeLa and CaSki cells, suggesting the
critical role of the mitochondrial pathway in their
apoptosis-inducing effect. This study also demonstrated the
wound-healing potential of curcumin, and the results of
transwell assays showed that curcumin treatment inhibited HeLa
and CaSki cell invasion and migration in a dose-dependent manner
compared with the control treatment. Curcumin also downregulated
the expression of Bcl-2, N-cadherin, and Vimentin and
upregulated the expression of Bax, C-caspase-3, and E-cadherin
in both cell lines. Further research showed that curcumin also
selectively inhibited the expression of the viral oncoproteins
E6 and E7, as demonstrated by western blot analysis; moreover,
the downregulation of E6 was more significant than that of E7.
In summary, our research shows that curcumin regulates the
apoptosis, migration, and invasion of cervical cancer cells, and
the mechanism may be related to its ability to downregulate E6.
This study provides a foundation for future research on the
prevention and treatment of cervical cancer.
Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c
cascade to suppress colorectal cancer metastasis
Cell Death & Differentiation | June 2023 Curcumin has
potential as a preventive and therapeutic agent for colorectal
cancer, as it suppresses many hallmarks of cancer cells and
exhibited promising effects in preclinical and clinical studies.
For example, the addition of daily oral curcumin to FOLFOX
chemotherapy significantly prolonged the progression-free
survival and overall survival of patients with metastatic
colorectal cancer. Moreover, curcumin showed improved erytrocyte
sedimentation rate and C-reactive protein/CRP serum levels of in
stage 3 colorectal cancer patients and improved their quality of
life. Daily oral curcumin given to patients with advanced
colorectal cancer refractory to standard chemotherapy, resulted
in stable disease in 5 of 15 individuals within 4 months of
follow-up evaluation. When curcumin was given in combination
with mesalamine it resulted in remissions of patients with
ulcerative colitis. Furthermore, in familial adenomatous
polyposis/FAP patients a combination of curcumin and quercetin
reduced the number and size of ileal and rectal adenomas without
appreciable toxicity. The addition of curcumin to cancer therapy
is of great interest, since a phase I clinical study showed that
the addition of curcumin to FOLFOX treatment is safe and
tolerable in patients with metastatic colorectal cancer at doses
up to 2 grams daily. Moreover, oral consumption of up to 3600 mg
curcumin leads to curcumin concentrations in human colorectal
mucosa which are in the range of the concentration used in this
study.
Curcumin inhibits proliferation of hepatocellular
carcinoma cells by blocking PTPN1 and PTPN11 expression
Oncology Letters | June 2023 Curcumin was demonstrated to
inhibit the growth of hepatocellular carcinoma cells tumors in
mice. Immunohistochemistry results demonstrated that the protein
expression levels of PTPN1 and PTPN11 in the curcumin group were
significantly lower compared with those in the control group. In
conclusion, these results demonstrated that curcumin inhibits
the proliferation of HCC cells by inhibiting the expression of
PTPN1 and PTPN11.
Pharmacological
Mechanisms and Clinical Applications of Curcumin: Update
Aging and Disease | June 2023 Curcumin, a
well-known hydrophobic polyphenol extracted from the rhizomes of
turmeric (Curcuma longa L.), has attracted great interest in the
last ten years due to its multiple pharmacological activities. A
growing body of evidence has manifested that curcumin has
extensive pharmacological activities including
anti-inflammatory, anti-oxygenation, lipid regulation,
antiviral, and anticancer with hypotoxicity and minor adverse
reactions. By reviewing the latest research progress of
curcumin, we believe that curcumin has a broad clinical
application prospect for its wide range of pharmacological
activities with few side effects.
Effect of curcumin on rheumatoid arthritis: a
systematic review and meta-analysis
Frontiers in Immunology | June 2023 Curcumin is beneficial
for rheumatoid arthritis treatment. Inflammation levels and
clinical symptoms in patients with rheumatoid arthritis can be
improved by curcumin supplementation. Large sample randomized
controlled trials on the effects of curcumin on patients with
rheumatoid arthritis are needed in the future. Curcumin is the
most important chemical component of turmeric, which can exert
antioxidant, anti-inflammatory, anti-angiogenic and anti-tumor
pharmacological effects without significant adverse effects.
Previous studies have shown that curcumin and curcuminoids in
turmeric could provide good protection against many chronic
diseases in the body by inhibiting inflammatory responses,
lowering blood lipids, and improving blood sugar. Curcumin in
turmeric can effectively inhibit inflammatory reactions and
reduce symptoms such as pain and swelling. In recent years, it
was found that curcumin could alleviate some symptoms in some
autoimmune diseases such as rheumatoid arthritis and
inflammatory bowel disease. The researchers have conducted
numerous studies to evaluate the pharmacological effects and
clinical applications of turmeric and curcumin on rheumatoid
arthritis treatment. Curcumin, a pure natural compound derived
from the roots of turmeric, is one of the most active components
of polyphenolic curcuminoids. Curcumin compound has been found
to exert anticancer effects on a variety of molecular mechanisms
through Nrf2 regulation. Curcumin is effectively used for
obesity therapy because it is a lipophilic molecule that can
rapidly penetrate cell membranes, and may be associated with
lipid metabolism, gut microbiota, and anti-inflammatory
potential. Curcumin is also known as “seasoning of life” by its
well-known antibacterial, anti-inflammatory, antioxidant,
antitumor, antifungal and pro-apoptotic effects. Curcumin has
been shown to improve symptoms and delay disease cycles in
rheumatoid arthritis patients. The multiple double bonds
in curcumin endow it with trapping free radical electrons,
antioxidant activity and anti-inflammatory effects. Curcumin is
beneficial for rheumatoid arthritis treatment. Inflammation
levels and clinical symptoms in patients with rheumatoid
arthritis can be improved by curcumin supplementation.
Curcumin inhibits colon cancer malignant progression
and promotes T cell killing by regulating miR-206 expression
Clinical Anatomy | June 2023 Curcumin, as a traditional
Chinese medicine extract with anti-tumor and anti-inflammatory
effects, can affect the development of diverse human diseases
including cancer. Curcumin treatment restrained proliferation
and accelerated apoptosis of colon cancer cells. It elevated
miR-206 expression, which in turn affected colon cancer cell
function. miR-206 enhanced colon cancer cell apoptosis and
inhibited PD-L1 expression; thus, curcumin enhanced the killing
effect of T cells on tumor cells by suppressing PD-L1 through
inhibiting the JAK/STAT3 pathway. Patients with high expression
of miR-206 had better survival rates than those with low
expression. Curcumin can regulate miR-206 expression and inhibit
the malignant behavior of colon cancer cells and enhance T cell
killing through the JAK/STAT3 pathway.
Turmeric supplementation improves markers of
recovery in elite male footballers: a pilot study
Frontiers in Nutrition | June 2023 Curcumin, a natural
polyphenol found in high concentrations in turmeric, has
anti-inflammatory, antioxidant, and analgesic properties, making
it a candidate to accelerate post-exercise recovery.
Laboratory-based studies of cycling, running and eccentric
loading protocols (e.g., downhill running, eccentric resistance
exercises), have shown that curcumin supplementation before and
after an exercise period can reduce subjective soreness,
attenuate haematological inflammatory markers, and improve
subsequent exercise performance. However, there is an absence of
applied studies in elite cohorts, likely due, in part, to
challenges associated with conducting research in elite cohorts.
One study, in elite rugby players, found that curcumin
attenuated muscle damage and limited loss of muscle function
after a muscle damaging protocol, while one other study in youth
team male footballers found that curcumin attenuated DOMS and
loss of muscle function after match-play. The supplement
also contained piperine, an adjuvant that can greatly improve
bioavailability of curcumin. High doses of curcumin (up to 12 g
per day) are pharmacologically safe and well tolerated in
humans. Piperine slows the metabolism of curcumin by inhibiting
hepatic and intestinal glucuronidation. Previous studies have
shown that administering curcumin with piperine can increase
serum concentrations of curcumin by up to 2000%, indicating that
glucuronidation inhibition may be the major mechanism of
increasing curcumin bioavailability. As such, the formulation of
the supplement administered in the current study, which
contained 35 g of raw turmeric root, (estimated to contain
1,400 mg of curcumin) and 10 mg of piperine, may have helped to
increase serum concentrations of curcumin such that it could
exert its biological action, whilst the mode of administration
may have encouraged greater adherence.
Cardioprotective effect of curcumin on myocardial
ischemia/reperfusion injury: a meta-analysis of preclinical
animal studies Frontiers in Pharmacology |
June 2023 A total of 38 studies were included in this
meta-analysis, and the results suggested that curcumin
significantly reduced the myocardial IS, improved cardiac
function parameters, downregulated serum myocardial enzyme,
improved antioxidant ability, decreased serum inflammatory
cytokines, and myocardial apoptosis index. In conclusion, our
results demonstrated a significant cardioprotective effect of
curcumin at multiple levels in animal models of myocardial I/R
injury. The results of this study showed that curcumin
significantly reduces myocardial IS, improves cardiac function,
downregulates myocardial enzyme levels, inhibits oxidative
stress, decreased serum inflammatory cytokines, and myocardial
apoptosis index to play a cardioprotective role in animal models
of myocardial I/R injury. This meta-analysis suggests that
curcumin has excellent potential for the treatment of myocardial
I/R injury in animal models. Curcumin treatment significantly
improved myocardial infarction size standard mean difference
(SMD) = −5.65; 95% confidence interval. In addition, curcumin
treatment improved cardiac function, myocardial injury enzymes,
and oxidative stress levels in animal models of myocardial I/R
injury. The results showed that curcumin treatment downregulated
serum inflammatory cytokine levels and myocardial apoptosis
index. Conclusion: This meta-analysis suggests that curcumin has
excellent potential for the treatment of myocardial I/R injury
in animal models. Curcumin was proven to be well tolerated at
high oral doses (12 g/d) and was generally considered to be safe
(Lao et al., 2006; Gupta et al., 2013; Prasad et al., 2014).
Recent studies have shown that curcumin protects cardiomyocytes
from myocardial I/R injury through multiple and diverse
mechanisms (Wang et al., 2018a; Mokhtari-Zaer et al., 2018; Wu
et al., 2021a; Pawar et al., 2022). Curcumin has been shown to
improve cardiac function after myocardial I/R injury by reducing
extracellular matrix degradation and inhibiting collagen
synthesis via the TGFβ/Smad signaling pathway (Wang et al.,
2012). In addition, curcumin attenuates oxidative damage and
inhibits cardiomyocyte apoptosis by activating the JAK2/STAT3
signaling pathway, thereby ameliorating myocardial I/R injury
(Liu et al., 2017a).
Curcumin as a therapeutic agent in cancer therapy:
Focusing on its modulatory effects on circular RNAs
Phytotherapy Research | June 2023 Curcumin, a natural
polyphenol compound, has been identified as an effective
therapeutic agent against cancer that exerts its anti-tumor
activities by up/downregulating signaling mediators and
modulating various cellular processes, including angiogenesis,
autophagy, apoptosis, metastasis, and epithelial–mesenchymal
transition (EMT). Since almost 98% of genomic transcriptional
production is noncoding RNAs in humans, there is evidence that
curcumin exerts therapeutic effects through the alterations of
noncoding RNAs in various types of cancers. It has been shown
that curcumin modulated various circRNAs. In this article, we
reviewed the pharmacokinetics of curcumin, its anti-cancer
activities, as well as the biology and structure of circRNAs.
Our main focus was on how curcumin exerts anti-cancer functions
by modulating circRNAs and their target mRNAs and pathways.
Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c
cascade to suppress colorectal cancer metastasis
Cell Death & Differentiation | June 2023 Curcumin is a
polyphenol derived from the rhizome of the turmeric plant
(Curcuma longa) and has been a popular food additive in Eastern
cuisine. In addition, it has been used for centuries in
traditional Chinese and ayurvedic medicine. Notably, curcumin
has potential as a preventive and therapeutic agent for CRC, as
it suppresses many hallmarks of cancer cells and exhibited
promising effects in preclinical and clinical studies. For
example, the addition of daily oral curcumin to FOLFOX
chemotherapy (folic acid/5-fluorouracil/oxaliplatin)
significantly prolonged the progression-free survival and
overall survival) of patients with metastatic CRC. Moreover,
curcumin showed improved erytrocyte sedimentation rate and
C-reactive protein/CRP serum levels of in stage 3 CRC patients
and improved their quality of life. Daily oral curcumin given to
patients with advanced colorectal cancer refractory to standard
chemotherapy, resulted in stable disease in 5 of 15 individuals
within 4 months of follow-up evaluation. When curcumin was given
in combination with mesalamine it resulted in remissions of
patients with ulcerative colitis/UC. Furthermore, in familial
adenomatous polyposis/FAP patients a combination of curcumin and
quercetin reduced the number and size of ileal and rectal
adenomas without appreciable toxicity. As the clinical studies
only included small numbers of patients, larger, targeted and
prospective clinical trials are required to establish curcumin
in clinical practice. Curcumin was shown to affect the
expression of non-coding RNAs in CRC cells. Also miR-34a, a
p53-inducible microRNA with tumor-suppressive capacities, was
induced by exposure to curcumin. our results provide a plausible
mechanism for the effects that have been ascribed to curcumin in
the prevention and therapy of colorectal cancer and other
malignancies. The members of the miR-34 family are frequently
silenced in colorectal tumors by DNA methylation. There is
evidence that curcumin can reactivate CpG methylated genes.
Therefore, CpG-methylation of miR-34a/b/c is presumably not an
obstacle for treatment of CRC with curcumin. Originally this
study was intended to determine the mode of action of curcumin
during tumor prevention. In that scenario, miR-34a/b/c should
not be silenced by CpG-methylation. We showed that the
anti-tumor effects of curcumin are less pronounced in
miR-34-deficient cells. Therefore, it will be important to
investigate the in vivo effects of curcumin on CRC treatment and
prevention with respect to miR-34 expression in the future. For
example, future experiments should include the treatment of wt
and miR-34 knockout mouse models of CRC with curcumin and/or
chemotherapy. Howells et al. showed in a phase IIa clinical
study that the addition of curcumin to FOLFOX treatment
significantly improved the progression free and overall
survival. The addition of curcumin to cancer therapy is of great
interest, since a phase I clinical study showed that the
addition of curcumin to FOLFOX treatment is safe and tolerable
in patients with metastatic CRC at doses up to 2 grams daily.
Moreover, oral consumption of up to 3600 mg curcumin leads to
curcumin concentrations in human colorectal mucosa which are in
the range of the concentration used in this study. In the
future, the findings presented here may be exploited for the
development of therapeutic approaches that aim at restoring the
tumor suppressive function of the p53/miR-34 pathway.
Curcumin
Enhances the Abscopal Effect in Mice with Colorectal Cancer by
Acting as an Immunomodulator Pharmaceutics
| June 2023 Curcumin has been shown to exert anti-tumor and
immunomodulatory properties in several studies. Curcumin
suppresses tumor growth by generating reactive oxygen species
(ROS) and inducing apoptosis. Curcumin triggers apoptosis in
HCT-116 cells by inhibiting NF-κB activation and downstream
pathways. Curcumin has been found to cause more DNA damage and
cell deaths in Panc-1 and MiaPaCa-2 cells when combined with RT.
Additionally, curcumin exerts immunomodulation potential and
slows tumor progression. For instance, curcumin augments tumor
inhibition by enhancing the proliferation and activation of T
cells. Curcumin can also suppress tumor growth by repressing the
generation and activity of TGF-β-induced regulatory T cells. We
chose curcumin for combination treatment due to its anti-tumor
and immunomodulatory abilities. Curcumin has been found to
repress the expression of NF-κB and PD-L1. Liao et al. reported
that curcumin suppresses PD-L1 levels and improves the tumor
immune microenvironment in tongue squamous cell carcinoma. The
results showed that combining curcumin with RT resulted in the
most significant tumor inhibition in primary and secondary
tumors. This finding suggests that curcumin has the potential to
enhance the abscopal effect and improve treatment outcomes.
Curcumin has been found to improve the effectiveness of
different treatments in various cancers. For example, Hussain et
al. summarized that curcumin can augment the efficacy of
cisplatin and reduce treatment resistance by increasing ROS
generation and triggering apoptosis cascades in multiple cancer
types. A combination of curcumin and doxorubicin has also been
shown to help tumor control by disturbing cell cycle progression
and the balance between apoptosis and anti-apoptosis in head and
neck cancer. Curcumin has also been combined with FLLFOX
chemotherapy for treating patients with metastatic colorectal
cancer, resulting in significant improvement in overall and
progression-free survival. However, further research is needed
to fully elucidate the mechanisms underlying the beneficial
effects of curcumin in cancer treatment. Curcumin enhances
radiosensitivity by regulating epigenetics, DNA damage repair,
and apoptosis in various cancers, including nasopharyngeal
cancer, bladder cancer, and glioblastoma. Curcumin can also
enhance radiotherapy through anti-inflammatory mechanisms.
Additionally, curcumin may enhance radiotherapy through
anti-inflammatory mechanisms. Our findings demonstrate that
curcumin enhances the abscopal effect in a bilateral CT26
tumor-bearing mouse model by suppressing NF-κB and downstream
proteins, elevating IL-1β and IL-6, and modulating the overall
tumor immune microenvironment, thereby enhancing tumor
suppression. We also validated that curcumin enhances RT
outcomes and boosts the anti-tumoral immune responses in
bilateral CT26-luc tumor-bearing mice by performing a
biodistribution study of 111In-DOTA-anti-OX40 mAb, ELISA assay,
and Western blot. These results suggest that curcumin acts as an
immunomodulator to improve RT outcomes.
Effect
of Curcumin and Coenzyme Q10 Alone and in Combination on
Learning and Memory in an Animal Model of Alzheimer’s Disease
Biomedicines | June 2023 Curcumin has a
wide range of biological and pharmacological effects, including
those that are antibacterial, anti-inflammatory, antioxidant,
anti-tumour, anti-protozoa, and anti-HIV. This has been
demonstrated by modern medicine. According to the Joint Nations
and World Health Organization Expert Committee on Food Additives
(JECFA), curcumin is regarded as a safe chemical and is hence
appropriate for everyday dietary usage. Curcumin is a viable
drug candidate for the treatment of complicated disorders such
as Alzheimer’s disease and its related cognitive loss because of
its pleiotropic effects and good safety profile. Curcumin has
demonstrated a dose–response relationship, with a higher dose
(200 mg/kg b.w. p.o.) being more effective than a lower dose
(100 mg/kg b.w. p.o.). We may infer from our results that
curcumin at higher doses and its combination with coenzyme Q10
have a significant impact on cognitive impairment in animal
models of Alzheimer’s disease and can be utilised alone or as an
add-on therapy for the condition. The bioavailability of
curcumin was significantly increased by 2000% when 20 mg of
piperine, which is extracted from black pepper, was also taken
as a supplement. Curcumin has a learning and memory
enhancement effect and a higher dose is comparatively more
effective than a lower dose and it has shown a
dose–response effect. The effects of the combination of curcumin
and coenzyme Q10 on learning and memory were significant and
greater than when both drugs were given alone and were
comparable to Memantine. The results of the present study are
encouraging and may reveal the importance of curcumin and
coenzyme Q10 herbal drugs and nutrients in impaired cognition
states. As a result, curcumin, coenzyme Q10, and their
combination, which has demonstrated the greatest benefit, may be
effective in the management of learning- and memory-impaired
states as an alternative, supplemental, or even preventive
medication. These medications, alone or in combination, can be
taken by patients of any age for a longer period of time without
experiencing any negative side effects.
Journal of Pharmaceutical Research Curcumin from
turmeric is an extremely efficient agent in increasing
cholesterol uptake by the liver cells
Journal of Pharmaceutical Research | May 2023 Curcuma longa
decreased total cholesterol, TG, LDL cholesterol 16.10, 20.01,
and 17.59 mg/dl respectively. Curcuma longa, Fenugreek leaves
and Lemon are mild to moderately effective hypolipidemic herbs
to lower total plasma cholesterol, triglycerides, and LDL
cholesterol. Curcumin reduces both the oxidation and circulation
of oxidized levels of LDL cholesterol which leads to reduction
in the occurrence or treatment of already present
atherosclerosis in the subjects. Research has revealed that
curcumin from turmeric is an extremely efficient agent in
increasing cholesterol uptake by the liver cells. Several
independent studies have shown that curcumin increases the
expression of cholesterol and lipoprotein receptors on the liver
cells. Curcumin also in- creases cholesterol and bile acids
excretion in feces. Additionally, curcumin also increases the
amount of ABC (ATP-binding cassette) transporters. Phenolics in
Curcuma Longa have potential health benefits mainly due to their
antioxidant properties such as reactive oxygen species (ROS)
scavenging and inhibition, electrophile scavenging and metal
chelation.
Curcumin
Attenuates Delayed-Onset Muscle Soreness and Muscle Function
Deficits Following a Soccer Match in Male Professional Soccer
Players International Journal of Sports
Physiology and Performance | May 2023 Curcumin attenuated
deficits in CMJ (P ≤ .004) and RSI (P ≤ .001) and reduced
Delayed-Onset Muscle Soreness (P ≤ .004) at all postmatch time
points (except 60 h post for RSI). The greatest difference
between control and curcumin was 12 hours post for CMJ
(P < .001, 1.91 [4.40] cm, 95% CI, 1.25 to 2.57, g = 0.36) and
RSI (P = .003, 0.40 [0.41] AU, 95% CI, 0.17 to 0.63, g = 0.90)
and 36 hours post for Delayed-Onset Muscle Soreness (P < .001,
47 [23] mm, 95% CI, −67 to −27, g = 2.12). Conclusions: Curcumin
intake <36 hours after a soccer match attenuated Delayed-Onset
Muscle Soreness and muscle function deficits, suggesting that
curcumin may aid recovery in professional male soccer players.
The
effects of curcumin on astrocytes in common neurodegenerative
conditions Mini-Reviews in Medicinal
Chemistry | May 2023 Curcumin, with multiple special
properties, has been effectively prescribed to manage various
diseases. It has hepato-protective, anti-carcinogenic,
cardio-protective, thrombo-suppressive, anti-inflammatory,
chemo-therapeutic, anti-arthritic, chemo-preventive, and
anti-oxidant activities. In the current review, the effects of
curcumin on astrocytes in common neurodegenerative conditions,
such as Huntington's disease, amyotrophic lateral sclerosis,
multiple sclerosis, Alzheimer's disease, and Parkinson's
disease, are discussed. Hence, it can be concluded that
astrocytes play a critical role in neurodegenerative diseases,
and curcumin is able to directly modulate astrocyte activity in
neurodegenerative diseases.
Curcumin reduces paclitaxel resistance in ovarian
carcinoma cells by upregulating SNIP1 and inhibiting NFκB
activity Biochemical Pharmacology | May
2023 Curcumin inhibits NFκB activity by modulating the
EGR1/SNIP1 axis to attenuate p65 acetylation and protein
stability in Txr cells. These findings provide a new mechanism
to account for the effects of curcumin in inducing apoptosis and
reducing paclitaxel resistance in ovarian cancer cells. Curcumin
has been described as having unique anticancer activity,
including inducing apoptosis and inhibiting proliferation and
invasion of tumors by suppressing a variety of cellular
signaling pathways. It was reported that curcumin induced cell
apoptosis and increased paclitaxel sensitivity by interfering
with NFκB, p53, and caspase-3 signaling. Moreover, curcumin’s
anticancer properties have primarily been attributed to blocking
the transcriptional factor NFκB activity. Curcumin, a dietary
phytochemical obtained from the dried rhizomes of Curcuma longa
(turmeric), has been used as a food additive and as a form of
traditional herbal medicine. In combination with 5-fluorouracil
(5-FU), docetaxel, or paclitaxel, curcumin significantly
enhanced chemotherapy sensitivity and produced significant
health benefits]. The anticancer properties of curcumin have
been primarily attributed to its ability to block the
transcriptional factor NFκB, which is a master regulator of
inflammation, cell proliferation, apoptosis, and drug
resistance. Therefore, curcumin may be used against
paclitaxel-resistant cancer cells induced by TLR4 signaling,
which activates NFκB and upregulates downstream taxol-resistance
genes. In addition, curcumin has been reported to inhibit NFκB
activity.
Effects of Curcumin on Axon Growth and Myelin Sheath
Formation in an In Vitro Model
Neurochemical Research | May 2023 Although the beneficial
effects of curcumin, extracted from rhizomes of the ginger
family genus Curcuma, on the repair and regeneration of nerves
have been evaluated in vitro, there are few studies concerning
its effects on axon myelination. We found a significant increase
in expression of all six proteins following curcumin treatment,
with a corresponding increase in the levels of MBP, MPZ,
Krox-20, and Oct-6 mRNA. The results suggested that curcumin can
promote the growth of axons by upregulating the expression of
GAP-43 and MAP-2, stimulate synthesis and secretion of
myelin-related proteins, and facilitate formation of the myelin
sheath in axons by upregulating the expression of Krox-20 and
Oct-6. Therefore, curcumin could be widely applied in future
strategies for the treatment of nerve injuries.
Curcumin Improves Diabetic Cardiomyopathy by
Inhibiting Pyroptosis through AKT/Nrf2/ARE Pathway Mediators of
Inflammation Mediators of Inflammation |
May 2023 Curcumin is a natural antioxidant that protects
cells from inflammatory damage and has therapeutic effects in
diseases such as myocardial, kidney, and liver injuries. Li et
al.’s report found that curcumin can improve mercuric
chloride-induced liver injury through the Nrf2/ARE pathway. Zhao
et al.’s study found that curcumin inhibited autophagic death
caused by HgCl2 through the PI3K/AKT/Nrf2 pathway, thereby
improving spleen damage. Therefore, curcumin is a natural
agonist of Nrf2, which provides a good pharmacological basis for
the treatment of diabetic cardiomyopathy. Current research has
found that curcumin has a good therapeutic effect on the
complications of diabetes. Curcumin can inhibit the NF-κB/p65
pathway in the nervous system of diabetic rats, increasing the
activity of superoxide dismutase and reducing the level of
inflammatory factors. ALTamimi found that curcumin could inhibit
the PKCβ/p66shc axis and activate FOXO-3a, reversing diabetic
nephropathy in rats. The present study found that curcumin can
inhibit the progression of pyroptosis in diabetic
cardiomyopathy, reduce the degree of myocardial fibrosis, and
inhibit the decline of cardiac function by regulating the
AKT/Nrf2/ARE pathway. Therefore, our findings support the
therapeutic potential of curcumin and provide a new theoretical
basis for the treatment of diabetic cardiomyopathy. This study
found that curcumin can promote the transfer of Nrf2 into the
nucleus through the AKT pathway and increase the expression of
the downstream antioxidant factors HO-1 and GCLC. These effects
cleared the accumulation of ROS in diabetic cardiomyocytes,
alleviated mitochondrial damage, inhibited the progression of
pyroptosis, and had a role in the treatment of diabetic
cardiomyopathy.
Curcumin alleviated oxidation stress injury by
mediating osteopontin in nephrolithiasis rats
Acta Cirúrgica Brasileira | May 2023 Curcumin could reduce
the oxidative stress damage caused by EG-induced kidney stones.
Curcumin (Cur) is a polyphenolic substance isolated from the
turmeric rhizome. Curcumin is the main active component of
turmeric, and it has various functions, including antioxidant,
anti-inflammatory, antifibrosis8, antibacterial and antitumor
activities, and protection from oxidative damage in the kidney.
Animal models of oxidative damage to kidney tissue and kidney
stones have proven that curcumin can reduce the expression of
inflammation-related factors, and induce anti-inflammatory
factors to inhibit the activation of the MAPK/ERK, TGF-β/Smad,
and PPAR-γ pathways. In addition, curcumin could induce the
antioxidant response in the kidney, and nuclear factor Nrf2 to
play a regulatory role, inhibit mitochondrial dysfunction,
reduce inflammation and prevent oxidative stress damage. Studies
have shown that curcumin exhibits important renal protection and
stone suppression effects in kidney diseases. The subcutaneous
injection of curcumin could alleviate the oxidative stress
damage of calcium oxalate kidney stones induced by EG within a
specific dose range. Curcumin may dissolve calcium oxalate
stones in the renal tubules of rats and reduce the oxidative
damage of calcium oxalate stones to the kidneys. Therefore,
curcumin could be used as a new drug candidate to treat kidney
stones.
Anti-Allergic
Effect of Dietary Polyphenols Curcumin and Epigallocatechin
Gallate via Anti-Degranulation in IgE/Antigen-Stimulated Mast
Cell Model: A Lipidomics Perspective
Metabolites | May 2023 Both curcumin and EGCG significantly
inhibited degranulation as they suppressed the release of β-hexosaminidase,
interleukin-4, and tumor necrosis factor-α from the
IgE/antigen-stimulated mast cell model. Remodeling patterns
(lipid response and composition) of curcumin intervention were
considerably similar to those of EGCG, lipid metabolism was more
potently disturbed by curcumin. Seventy-eight percent of
significant differential lipids upon IgE/antigen stimulation
could be regulated by curcumin/EGCG. LPC-O 22:0 was defined as a
potential biomarker for its sensitivity to IgE/antigen
stimulation and curcumin/EGCG intervention. The key changes in
diacylglycerols, fatty acids, and bismonoacylglycerophosphates
provided clues that cell signaling disturbances could be
associated with curcumin/EGCG intervention. Our work supplies a
novel perspective for understanding curcumin/EGCG involvement in
antianaphylaxis and helps guide future attempts to use dietary
polyphenols. Curcumin got approved to be “generally recognized
as safe” (GRAS) by the US Food and Drug Administration (FDA).
Two typical dietary polyphenols, curcumin and EGCG, were
confirmed to show anti-allergic potential in the present study.
Both curcumin and EGCG significantly suppressed the release of
β-hexosaminidase, IL-4, and TNF-α from IgE/antigen-stimulated
RBL-2H3 cells. As compared to the alteration pattern associated
with IgE/antigen-stimulated degranulation (Veh vs. AG), the
lipidome modulation by curcumin/EGCG could be identified (Cur
vs. AG and EGCG vs. AG). Comprehensive lipidomics analysis
revealed that the ability to disturb lipid metabolism was
stronger with curcumin than EGCG, in accordance with the
superior ability of curcumin to suppress the degranulation
process. These key lipidome disturbances provide novel insights
into the effects of curcumin/EGCG intervention underlying the
progression of degranulation. Our findings open the possibility
of preventing immediate allergic reactions via
antigen-stimulated mast cells in vitro and will help guide
future attempts to use dietary polyphenols.
Curcumin and whey protein concentrate binding:
Thermodynamic and structural approach Food
Hydrocolloids | May 2023 Curcumin is a natural hydrophobic
polyphenol (Liu, Chen, Cheng, & Selomulya, 2016), first isolated
from the rhizome of turmeric (Curcuma longa), and it has a
varied range of beneficial biological activities. According to
recent studies, it is recognized that curcumin has the ability
to enhance human health, particularly due to its antioxidant,
anti-inflammatory, anticancer, antibacterial and antiviral
activities. For example, it was reported that curcumin reduces
cholesterol and platelet aggregation (Suresh & Srinivasan,
2010), inhibits proliferation of cancer cells (Naksuriya, van
Steenbergen, Torano, Okonogi, & Hennink, 2016; Shabaninejad et
al., 2020; Taebi et al., 2020) and improves digestion (Dulbecco
& Savarino, 2013). In addition, the curcumin , as an antiviral
and anti-inflammatory agent, might be helpful for both
prevention and treatment of COVID 19 (Dhar & Bhattacharjee,
2021; Jennings & Parks, 2020). Overall, the documented
anti-inflammatory and immunomodulatory effects of curcumin
(Yadav, Mishra, Singh, Mehrotra, & Singh, 2005) along with the
evidence on its anti-fibrotic effects (Gorabi et al., 2020) on
the lung tissue make it a promising candidate for the treatment
of COVID-19 (Dourado et al., 2021; Manoharan et al., 2020).
Cannabinoid compounds in combination with curcumin
and piperine display an anti-tumorigenic effect against colon
cancer cells Frontiers in Pharmacology |
May 2023 Evidence supported by experimental findings suggest
that micronutrients such as curcumin and piperine may present a
safer strategy in preventing tumorigenesis and its recurrence.
Recent studies demonstrated that piperine potentiates curcumin’s
inhibitory effect on tumor progression via enhancing its
delivery and therapeutic activity. It is possible to
reduce colorectal cancer death rate by as much as 90% through
inclusion of naturally existing bio-compounds with the
anti-cancer and anti-oxidant characteristics such as curcumin.
It is suggested that curcumin can selectively kill tumor cells
through its multifaceted metabolic effects, that culminate in
its anti-oxidant and anti-inflammatory activities (Hewlings and
Kalman, 2017). Several clinical trials classify curcumin as a
potential chemo-preventive and chemotherapeutic agent (Doello et
al., 2018). In exerting its anti-tumorigenic effects,
curcumin blocks angiogenesis, and negatively regulates cancer
cell cycle progression as well as metastatic activity. In
several combinatorial therapy approaches, where a secondary
active drug agent or drug candidate is co-administered with
curcumin, an increase in the therapeutic benefit from curcumin
has been reported in diverse cancer models (Baldi et al., 1839),
(Bolat et al., 2020), (Schmidt et al., 2020). Strikingly, the
second agent turns out to enhance curcumin-dependent anti-cancer
activity in a synergistic fashion in certain cases. Among the
numerous candidates tested so far, curcumin, piperine and
certain types of cannabinoids performed promisingly well in
colon carcinoma models as monotherapy agents. Piperine, a
dietary polyphenol isolated from black and long peppers,
distinguished with its intrinsic features, improves -not
only-curcumin’s existing anti-cancer activity, but also its
extremely poor bioavailability (Tang et al., 2017) (Tang et al.,
2017) As a single agent, piperine alone also displays
anti-mutagenic and anti-tumor activities (Chinta et al., 2015).
For example, this agent can inhibit the proliferation of colon
cancer cell lines via induction of a cell cycle arrest in the G1
phase, while it triggers apoptosis in prostate cancer models (Ouyang
et al., 2013), (Yaffe et al., 2015).
Curcumin can improve spinal cord injury by
inhibiting DNA methylation Molecular and
Cellular Biochemistry | May 2023 Curcumin is a natural
polyphenol from turmeric. It has anti-inflammatory, antioxidant,
and neuroprotective effects, and can mitigate the cell and
tissue damage caused by spinal cord injury. This report analyzed
the specific functions of DNA methylation in central nervous
system diseases, especially traumatic brain injury and spinal
cord injury. DNA methylation can regulate the level of gene
expressions in the central nervous system. Therefore,
pharmacological interventions regulating DNA methylation may be
promising for spinal cord injury.
Curcumin Improves Diabetic Cardiomyopathy by
Inhibiting Pyroptosis through AKT/Nrf2/ARE Pathway
Mediators of Inflammation | May 2023 Curcumin is a natural
antioxidant that protects cells from inflammatory damage and has
therapeutic effects in diseases such as myocardial, kidney, and
liver injuries. Li et al.’s report found that curcumin can
improve mercuric chloride-induced liver injury through the
Nrf2/ARE pathway. Zhao et al.’s study found that curcumin
inhibited autophagic death caused by HgCl2 through the
PI3K/AKT/Nrf2 pathway, thereby improving spleen damage.
Therefore, curcumin is a natural agonist of Nrf2, which provides
a good pharmacological basis for the treatment of diabetic
cardiomyopathy. Current research has found that curcumin has a
good therapeutic effect on the complications of diabetes.
Curcumin can inhibit the NF-κB/p65 pathway in the nervous system
of diabetic rats, increasing the activity of superoxide
dismutase and reducing the level of inflammatory factors. Al-Tamimi
found that curcumin could inhibit the PKCβ/p66shc axis and
activate FOXO-3a, reversing diabetic nephropathy in rats. The
present study found that curcumin can inhibit the progression of
pyroptosis in diabetic cardiomyopathy, reduce the degree of
myocardial fibrosis, and inhibit the decline of cardiac
function. Therefore, our findings support the therapeutic
potential of curcumin and provide a new theoretical basis for
the treatment of diabetic cardiomyopathy. This study found that
curcumin can promote the transfer of Nrf2 into the nucleus
through the AKT pathway and increase the expression of the
downstream antioxidant factors HO-1 and GCLC. These effects
cleared the accumulation of ROS in diabetic cardiomyocytes,
alleviated mitochondrial damage, inhibited the progression of
pyroptosis, and had a role in the treatment of diabetic
cardiomyopathy.
The Combined Effect of Curcumin and Crocin on the Reduction of
Inflammatory Responses in Arthritic Rats
Current Medicinal Chemistry | April 2023 Crocin,
curcumin and crocin + curcumin administration showed effective
anti-arthritic effects owing to their anti-inflammatory effects.
Therefore, crocin and curcumin, either alone or in combination,
can be a suitable treatment modality for rheumatoid arthritis.
The Apoptotic Activity of Curcumin Against Oral
Cancer Cells Without Affecting Normal Cells in Comparison to
Paclitaxel Activity Applied Biochemistry
and Biotechnology | April 2023 Curcumin and paclitaxel (PTX)
have significant anti-cancer activity against normal human
gingival fibroblast and tongue squamous cell carcinoma
fibroblast cell lines. The results showed that curcumin (13.85
µg mL−1) and PTX (8.17 µg mL−1) significantly inhibited TSCCF
cell viability, with no significant effect on normal HGF cells.
For TSCCF, the results showed the highest necrosis was achieved
with curcumin (58.8%) and PTX (39%) as compared to the control
(2.99%). In conclusion, the results confirmed that
curcumin is more specific to the oral cancer cells but not
normal cells by inducing apoptosis in a dose- and time-dependent
manner, with decreased TSCCF cell viability.
Curcumin
Epigenetically Represses Histone Acetylation of Echinocandin B
Producing Emericella rugulosa Physiologia
| April 2023 Analysis revealed suppression of the
echinocandin B levels in the cells treated with curcumin.
Curcumin was also found to repress the expression of different
ecd genes by several folds. Taken together, we conclude that
curcumin targets echinocandin B production by inhibiting histone
acetylation as well as disrupting interspecies consortium
communication, which eventually leads to a decrease in the
echinocandin B synthesis. The curcumin treatment to E.
rugulosa NRRL11440 showed severe impairment of the
echinocandin B production as supported by the HPLC analysis.
Curcumin treatment to E. rugulosa NRRL11440 was found to
suppress the echinocandin B antifungal biosynthesis by
repression of gene expression of a transcriptional factor ecdB
and an NRPS-coded ecdA which shows reduced cell susceptibility
against C. albicans. Curcumin may turn out to be an effective
histone acetyltransferase inhibitor for limiting acetylation on
the histone proteins.
Curcumin and chemokines: mechanism of action and
therapeutic potential in inflammatory diseases
Inflammopharmacology | April 2023 Curcumin, the major
component of the Curcuma longa rhizome, has various
pharmacological actions, including anti-inflammatory,
immune-regulatory, anti-oxidative, and lipid-modifying
properties. Curcumin is a safe phytochemical that elicits a wide
range of biological actions in the human body. It shows
anti-inflammatory, antioxidant, lipid-modulating,
anti-thrombotic, immunomodulatory, hepatoprotective,
anti-diabetic, anti-tumor, and neuroprotective actions (Qadir et
al. 2016; Bavarsad et al. 2019; Ghasemi et al. 2019; Iranshahi
et al. 2009; Panahi et al. 2017b; Parsamanesh et al. 2018;
Sahebkar and Henrotin 2016; Alidadi et al. 2020; Heidari et al.
2022; Vahedian-Azimi et al. 2022; Mohammed et al. 2021). In
addition, curcumin influences various cells and molecular
targets like growth factors, cytokines/chemokines, hormones,
transcription factors, cell adhesion molecules, protein kinases,
redox state enzymes, and receptors (Esatbeyoglu et al. 2012; H.
Zhou et al. 2011; Mashayekhi-Sardoo et al. 2021; Mohajeri et al.
2020; Soltani et al. 2021; Ganjali et al. 2017b;
Momtazi-Borojeni et al. 2018). The anti-inflammatory effects of
curcumin are mediated by downregulation in the activity of
cyclooxygenase-2 (COX-2), lipoxygenase (LOX), inflammasome, and
inducible nitric oxide synthase (iNOS) (Goel et al. 2008b,
2008a; Hassanzadeh et al. 2020). Moreover, curcumin also
inhibits IL-2, IL-6, IL-8, IL-12, TNF-α, macrophage inhibitory
protein (MIP), and the production of monocyte chemoattractant
protein-1 (MCP-1) pro-inflammatory cytokines and chemokines (Abe
et al. 1999), as well as down-regulates mitogen-activated and
janus kinases (Natarajan and Bright 2002; Siwak et al. 2005).
These biological effects appear to be achieved by
curcumin-mediated inhibition of NF-κB (Surh et al. 2001; Zhong
et al. 2012; Lee et al. 2005; Ji et al. 2009; Zhao et al. 2014).
The regulatory and anti-inflammatory effects of curcumin are
well established, and it exerts its pharmacological effects
through various molecular targets. In general, the biological
effects of curcumin are broadly thought to be achieved by
inhibition of NF-κB, although, more specifically, the actual
anti-inflammatory effects of curcumin are primarily mediated by
downregulation in the activity COX-2, LOX, and iNOS. Curcumin
can exert its inhibitory effects on chemokines, which generally
function as pro-inflammatory mediators and are responsible for
the recruitment of immune cells to sites of inflammation. As it
relates to the neuroprotective effects provided to neuroglia and
neurons, curcumin modulates the expression of different
chemokines and reduces degeneration, injuries, and deficits
associated with these cells' neuroinflammation. Moreover, the
inhibitory effect of curcumin on hepatic, cardiovascular,
pulmonary, and renal inflammatory conditions results in
decreased fibrosis and other inflammation-associated
histological complications. Lastly, in the case of cancer,
curcumin can inhibit chemokine expression, leading to inhibition
of tumor metastasis and activating specific chemokines that
recruit anti-tumor immune cells to the tumor microenvironment.
Curcumin Confers Anti-Inflammatory Effects in Adults Who
Recovered from COVID-19 and Were Subsequently Vaccinated: A
Randomized Controlled Trial Nutrients |
April 2023 Curcumin intake confers anti-inflammatory activity
and may be a promising prophylactic nutraceutical strategy for
COVID-19. 4 weeks of curcumin supplementation resulted in
significantly lower concentrations of proinflammatory cytokines
in adults who recovered from COVID-19 infection and were
subsequently vaccinated. Curcumin, a polyphenolic compound
derived from the rhizomes of turmeric (Curcuma Longa),
providing the spices’ yellow pigment, has been recognized for
its anti-inflammatory, antioxidant, anti-viral, and immune
modulating properties. Several studies have demonstrated the
effect of curcumin to inhibit inflammatory signaling pathways
such as nuclear factor-kappa B (NF-kB) in several cell types and
disease models and reduce the induction of several
proinflammatory cytokines and chemokines Given the evidence to
suggest the anti-viral and anti-inflammatory activity of
curcumin, the interest in this dietary compound as an adjunctive
strategy for COVID-19 has risen. Importantly, curcumin has also
exhibited good safety and tolerability profiles in clinical
trials, even at high doses. We demonstrated that curcumin
supplementation was associated with significantly lower levels
of the proinflammatory cytokines IL-6 and MCP-1, which increased
in the control group during the four-week trial period. These
findings indicate that curcumin supplementation may help to
control inflammation and support resilience.
Curcumin protects against doxorubicin induced
oxidative stress by regulating the Keap1-Nrf2-ARE and autophagy
signaling pathways Psychopharmacology |
April 2023 Curcumin relieves depressive-like state through
the mitigation of oxidative stress and the activation of
Nrf2-ARE signaling pathway. Curcumin, a yellow coloring agent
extracted from curcuma longa, has pharmacological
effects including antioxidant, anti-inflammatory,
immunomodulatory, and neuroprotective activities (Aggarwal and
Harikumar 2009; Maheshwari et al. 2006). Notably, curcumin’s
antioxidative properties hold a great deal of potential for
neuroprotective effect. Previous studies have reported that the
main mechanism of curcumin the treatment of oxidant
stress-related diseases was the activation of Nrf2 (Madiha and
Haider 2019; Yang et al. 2009). Our previous study have revealed
that curcumin relieves depressive-like state through the
mitigation of oxidative stress and the activation of Nrf2-ARE
signaling pathway (Liao et al. 2020). By activating Nrf2-ARE
signaling, curcumin exerts its chemopreventive effects via the
induction of antioxidant enzymes (Scapagnini et al. 2011).
Soetikno et al. have also reported that curcumin alleviates
oxidative stress, inflammation, and renal fibrosis in remnant
kidney through the Nrf2-keap1 pathway (Soetikno et al. 2013).
Scapagnini et al. have reported that curcumin strongly induces
HO-1 expression and activity in different brain cells via the
activation of Keap1-Nrf2-ARE signaling pathway (Scapagnini et
al. 2011). Balogun et al. have also reported that curcumin
exhibited its chemopreventive effect by selectively activating
the Nrf2-Keap1-ARE signaling pathway (Balogun et al. 2003).Our
present study has demonstrated that curcumin exhibited great
potential to reverse the depressive-like behavior in DOX-treated
rats. DOX-induced excessive oxidative stress causes the
upregulation of autophagy, and autophagy acts as an antioxidant
feedback response activated by the p62-Keap1-Nrf2 feedback loop.
The possible mechanism under behavior-modulating and
neuroprotective effects of curcumin is the activation of
p62-Keap1-Nrf2 signaling pathway.
Impact
of Curcumin Supplementation on Radiation Dermatitis Severity: A
Systematic Review and Meta-Analysis of Randomized Controlled
Trials Asian Pacific Journal of Cancer
Prevention | April 2023 Curcumin has recently attracted more
attention for managing the side effects of breast cancer
treatments. Based on the results of the present study, curcumin
has significant effects in reducing the severity of radiation
dermatitis in breast cancer patients receiving radiotherapy.
Amongst the wide range of medical herbs, curcumin is a component
of the turmeric plant and a potent antioxidant and
anti-inflammatory agent used to treat skin ailments, such as
scabies, acne, eczema, wrinkled skin, and wound healing. Some
clinical trial studies have shown that the effect of curcumin on
breast cancer dermatitis is beneficial(Khameneh et al., 2018;
Sarkhosh et al., 2019). For example, Okunieff et al. reported
curcumin might reduce cutaneous radiation toxicity in mice (Okunieff
et al., 2006). Hemati et al. demonstrated that oral curcumin is
effective in the prophylaxis of radiation-induced dermatitis in
breast cancer (Hemati et al., 2011). Curcumin can be
considered as an effective factor in inhibiting and controlling
radiation dermatitis in patients with BC and improving clinical
symptoms. Curcumin might reduce radiation dermatitis severity
compared to placebo through various molecular pathways, such as
reducing the levels of inflammatory cytokines.
Recent Progress in Understanding the Health Benefits of Curcumin
Molecules | March 2023 Among natural
compounds, curcumin, the main active component isolated from the
rhizome of Curcuma Longa L., is well known for its
beneficial effect on human health. Various biological activities
and therapeutic properties of curcumin are due to its chemistry;
in particular, phenolic hydroxyl groups, the central bis-α,
β-unsaturated β-diketone, double conjugated bonds, and methoxy
groups are responsible for its bio-pharmacological effects.
Inflammaging is a word used to describe the tight relationship
between low-grade chronic inflammation and aging that occurs
during physiological senescence in the absence of evident
infection. This condition has been linked to a broad spectrum of
age-related disorders in various organs, including the brain.
Inflammaging represents a highly significant risk factor for the
development and progression of age-related conditions, including
neurodegenerative diseases characterized by the progressive
dysfunction and degeneration of neurons in the brain and
peripheral nervous system. In the brain, curcumin acting on
microglia can inhibit the formation of reactive oxygen species
and other pro-inflammatory mediators that are believed to play a
pivotal role in many age-related diseases, such as Alzheimer’s
disease (AD), Parkinson’s disease (PD), and Huntington’s
disease. The studies presented in this Special Issue have
confirmed the multiple proprieties of curcumin that are
beneficial to human health. Our results suggest that curcumin
supplementation or curcumin supplementation together with a
combined change in dietary habits and/or implementation of
physical activity and/or lifestyle changes has positive effects
on the levels of certain blood biochemical parameters and waist
circumference.
Meta-Analysis
of Exploring the Effect of Curcumin Supplementation with or
without Other Advice on Biochemical and Anthropometric
Parameters in Patients with Metabolic-Associated Fatty Liver
Disease (MAFLD) International Journal of
Environmental Research and Public Health | March 2023
Curcumin is characterized by many desirable properties. It has
anti-inflammatory, antioxidant, and anticancer properties, among
others. Furthermore, importantly, it is safe and rarely causes
adverse symptoms. For this reason, it is used to treat or
support the treatment of many diseases, e.g., cardiovascular
diseases, inflammatory bowel diseases, breast, stomach,
pancreatic and lung tumors, dermatoses, allergic asthma, and
liver diseases. The use of curcumin supplementation or curcumin
supplementation together with changes in diet, lifestyle, and/or
physical activity led to statistically significant positive
changes in alanine aminotransferase (ALT), aspartate
aminotransferase (AST), fasting blood insulin (FBI), homeostasis
model assessment of insulin resistance (HOMA-IR), total
triglycerides (TG), total cholesterol (TC), and waist
circumference (WC). It appears that these therapeutic approaches
may be effective in alleviating Metabolic-Associated Fatty Liver
Disease (MAFLD).
The
Differential Antagonistic Ability of Curcumin against
Cytotoxicity and Genotoxicity Induced by Distinct Heavy Metals
Toxics | March 2023 Curcumin exhibits
various beneficial biological activities including being
anti-oxidant, anti-inflammatory, anti-tumor, and anti-bacterial.
A series of authoritative international institutions, such as
the Food and Drug Administration (FDA) in the USA and the Joint
FAO/WHO Expert Committee on Food Additives, have confirmed the
safety of curcumin in daily use and clinical treatment.
Depending on the outstanding biological properties, curcumin is
increasingly employed to antagonize heavy metals’ adverse
effects, mainly through anti-oxidation and metal chelation. For
instance, curcumin had been shown to have many therapeutic
properties on cadmium-induced organ toxicity by removing ROS and
inhibiting oxidative damage. In addition, Kabeer Abubakar et al.
showed that curcumin attenuates Pb-induced neurotoxicity by
inhibiting oxidative stress and chelating Pb ions. Curcumin
shows prominent detoxification specificity against different
types of heavy metals and toxic endpoints, which provides a new
clue for the better and targeted application of curcumin in
heavy metal detoxification. The protective efficacy of
curcumin for Cd- and As-induced toxicity was more obvious than
for Pb and Ni. Both anti-oxidation and metal chelation
contributed to the antagonistic efficiency of curcumin against
heavy metals. Considering the remarkable bioactivity and wide
application of curcumin in biomedicine, it is worthwhile to
further investigate the protective effect of curcumin against
many other contaminants and elucidate the underlying mechanism
in vitro and in vivo.
Curcumin effects on chronic obstructive pulmonary
disease: A systematic review Health Science
Reports | March 2023 Curcumin has antiproliferative and
anti-inflammatory effects by downregulating pro-inflammatory
cytokines. Besides, Curcumin accelerates the transcription of
genes which helps the expression of the antioxidant system by
reducing reactive oxygen species and leading to an
increase in the antioxidant defense system. Adding or replacing
Curcumin, a natural meal flavoring, may indicate advantages in
this era by its antiproliferative and anti-inflammatory effects.
Curcumin can inhibit alveolar epithelial thickness and
proliferation, lessen the inflammatory response, remodel the
airway, produce ROS, alleviate airway inflammation, hinder
emphysema and prevent ischemic complications. The findings of
our study suggest that Curcumin might be potentially a
beneficial food additive and could be effective in treating
chronic obstructive pulmonary disease for alternation or
addition to previous pharmacological managements. It has been
demonstrated that this impact is related to Curcumin's
modulatory effects on oxidative stress, cell viability, and
inflammation.
Curcumin: a natural organic component that plays a
multi-faceted role in ovarian cancer
Journal of Ovarian Research | March 2023 Curcumin, a natural
organic component obtained from Curcuma longa’s rhizomes, shows
abundant anti-tumor, antioxidant and anti-inflammatory
pharmacological activities, among others. Notably the anti-tumor
activity has aroused widespread attention from scholars
worldwide. Numerous studies have reported that curcumin can
delay ovarian cancer, increase its sensitivity to chemotherapy,
and reduce chemotherapy drugs’ side effects. It has been shown
considerable anticancer potential by promoting cell apoptosis,
suppressing cell cycle progression, inducing autophagy,
inhibiting tumor metastasis, and regulating enzyme activity.
Around 210 clinical trials on curcumin application have been
documented. Several clinical trials have shown that curcumin has
beneficial effects on serum markers of inflammation, weight loss
and glucose and lipid metabolism. Among other roles, this
natural polyphenolic compound acts as an antioxidant,
anti-aging, anti-inflammatory, lipid-modifying. As a
broad-spectrum anticancer drug, has been reported to selectively
kill cancer cells through various biological pathways without
toxic side effects on normal cells. These biological pathways
include the induction of apoptosis, cell cycle arrest, effects
on autophagy, inhibition of tumor cell metastasis, regulation of
enzyme activity and inhibition of the inflammatory response.
Clinical trials have shown that curcumin does not have toxic and
side effects at a dose of 8 g per day, which indicates its
safety.
The effect of curcumin-piperine on cardiometabolic, inflammatory
and oxidative stress factors and macular vascular density
Avicenna Journal of Phytomedicine | March 2023
Curcumin is a safe phytochemical with antioxidant,
anti-inflammatory, antidiabetic, and lipid-lowering effects. The
combination of curcumin with piperine (an alkaloid derived from
the plant Piper nigrum L.) has better gastrointestinal
absorption and reduces curcumin's systemic excretion. Piperine
increases the bioavailability of curcumin by binding to the
enzyme glucuronidase in the intestine, preventing
glucuronidation and reducing the excretion of curcumin from the
stool (Kaur, 2012). No significant adverse effects are
associated with supplementation with curcumin, even at doses
above 8 g/day (Mirzaei et al., 2017). Many regulatory proteins,
including chemokines, interleukins, hematopoietic growth
factors, and transcription factors, are modulated by curcumin,
thus reducing the inflammatory process (Peddada et al., 2019).
In several studies, curcumin has been shown to downregulate
tumor necrosis factor (TNF) -α (Li et al., 2013) and C- reactive
protein (Adibian et al., 2019). Curcumin supplementation
improved glycemic factors, low-density lipoprotein, very
low-density lipoprotein, and triglycerides in patients with
diabetes (Neerati et al., 2014). It also significantly lowered
blood glucose levels (Nabavi et al., 2015) and modulated retinal
disorders in diabetic rats. If the beneficial effects of
curcumin on diabetic retinopathy are observed, this safe, this
natural and inexpensive herbal supplement can be considered a
therapeutic solution in these patients.
Protective effects of curcumin and Ginkgo biloba
extract combination on a new model of Alzheimer’s disease
Inflammopharmacology | March 2023 Several experimental and
clinical investigations have shown that curcumin and its new
formulations protect against Alzheimer’s disease (Antona et al.
2021). Curcumin has been proven to have antioxidant,
anti-inflammatory, and neurotrophic properties, as well as the
ability to suppress apoptosis and hyper-phosphorylation of tau
protein (Yang et al. 2022). Our results provide strong evidence
for the hypothesis that ginkgo biloba extract increases
curcumin's plasma bioavailability and brain access, which may
improve curcumin’s effectiveness against characteristic symptoms
of Alzheimer’s disease. Moreover, it may support the idea that
ginkgo biloba extract and curcumin may be used together to
prevent the central pathological changes that result in the
occurrence of Alzheimer’s disease, and arrest the progression of
Alzheimer’s disease successfully.
The impact of curcumin supplementation on systemic
lupus erythematosus and lupus nephritis: A systematic review
Lupus | March 2023 Curcumin is the active ingredient in the
curry spice turmeric. It has anti-inflammatory properties due to
the inhibition of transcription factors and inflammatory
mediators such as nuclear factor-κβ (NF-κβ), cyclooxygenase-2
(COX2), lipoxygenase (LOX), tumor necrosis factoralpha
(TNF-alpha), and interleukin-1 (IL-1) and 6 (IL-6). Another
study suggested that curcumin reduced B cell-activating factor
(BAFF) when used for up to 8 weeks at 50 mg/kg/day. A reduction
in pro-inflammatory Th1 and Th17 percentages, IL-6 and
anti-nuclear antibody (ANA) levels were reported.
Curcumin Mitigates Neuropathic-Induce Muscle Atrophy
International Journal of Exercise Science | March
2023 Curcumin has been shown to
exert an anti-inflammatory effect, preserving muscle mass in
diabetic rats. Curcumin supplementation appears to mitigate this
inflammatory response and muscle mass loss.
Multiple mechanisms of curcumin targeting spinal
cord injury Biomedicine & Pharmacotherapy
Volume | March 2023 Curcumin acts as an
anti-inflammatory, antioxidant, anti-apoptotic and
neuroprotective agent in secondary spinal cord injury through
multiple pathways. As the main active ingredient in turmeric,
curcumin can play an important role in reducing inflammation and
oxidation, protecting the neurons, and ultimately reducing
spinal cord injury. This article reviews the effects of curcumin
on the repair of nerve injury, with emphasis on the various
mechanisms by which curcumin promotes the treatment of spinal
cord injury.
Efficacy of curcumin plus piperine
co-supplementation in moderate-to-high hepatic steatosis: A
double-blind, randomized, placebo-controlled clinical trial
Phytotherapy Research | February 2023 Curcumin + piperine
decreased waist circumference, systolic blood pressure, total
cholesterol, low-density lipoprotein-cholesterol, fasting blood
glucose, alanine transaminase and aspartate transaminase
compared with placebo. Curcumin + piperine may be considered as
an adjunct therapy to improve anthropometric measures, blood
pressure, lipid profile, blood glucose, and liver function in
NAFLD patients.
Curcumin-piperine co-supplementation and human health: A
comprehensive review of preclinical and clinical studies
Phytotherapy Research
| February 2023 The findings of this
comprehensive review show the beneficial effects of
curcumin-piperine in improving glycemic indices, lipid profile
and antioxidant status in diabetes, improving the inflammatory
status caused by obesity and metabolic syndrome, reducing
oxidative stress and depression in chronic stress and
neurological disorders, also improving chronic respiratory
diseases, asthma and COVID-19.
Curcumin
a Natural Phenol and Its Therapeutic Role in Cancer and
Photodynamic Therapy: A Review
Pharmaceutics | February 2023 Dietary-derived polyphenolic
compounds such as curcumin are stated to have anticancer
potential and related pharmacological benefits and receive
enormous attraction because of their beneficial health impact.
Curcumin is an extremely pleiotropic molecule that can mediate
cancer treatment as a chemopreventive or chemotherapy agent
without side effects. Curcumin and other turmeric-derived
products are labeled as safe by the Food and Drug Administration
(FDA, USA), and curcumin has achieved therapeutic pursuit in
treating metabolic diseases, immune-related diseases, and
cancer, owing to its vast biological target and with practically
no aftereffects. The structural characteristics of curcumin
improve its ability to bind with various biomacromolecules.
Mesenchymal
Stem Cells and Curcumin Effectively Mitigate Freund's
Adjuvant-induced Arthritis via their Anti-inflammatory and Gene
Expression Endocrine, Metabolic & Immune
Disorders | February 2023 Curcumin and BM-MSCs work together
to dramatically restore the high serum PGE2 and IL-17
levels and lower the IL-13 level in arthritic rats to normal
levels. Based on these findings, additive therapeutic effects on
rheumatoid arthritis occur from the combined treatment of
curcumin and BM-MSCs compared with their individual us. Thus, it
can be said that both curcumin and BM-MSCs are effective at
reducing inflammation while also having beneficial effects on
the ankle joint, thymus and spleen.
Modulatory properties of curcumin in cancer: A
narrative review on the role of interferons
Phytotherapy Research | February 2023 Curcumin, the active
ingredient of turmeric, is one of these herbal remedies with
many beneficial effects, including modulation of immunity.
Curcumin is beneficial in managing various chronic inflammatory
conditions, improving brain function, lowering cardiovascular
disease risk, prevention and management of dementia, and
prevention of aging. Several clinical studies have supported
this evidence, suggesting curcumin to have an immunomodulatory
and anti-inflammatory function.
The effect of Curcumin on metabolic parameters and
androgen level in women with polycystic ovary syndrome: a
randomized controlled trial BMC Endocrine
Disorders | February 2023 Recently curcumin was studied as
supportive therapy for a wide range of diseases such as type 2
diabetes which is one of the complications of polycystic ovary
syndrome PCOS. Based on a study on animals, curcumin can be
effective in improving insulin sensitivity and decreasing CRP
and IL-6 levels. Moreover, it was reported in a study on humans
that the edible intake of curcumin led to a significant decrease
in FBS, HOMA-IR, HbA1c, triglycerides, and total cholesterol
levels in patients with metabolic diseases. As seen in animal
experiments, the use of curcumin can lead to a decrease in
insulin resistance (one of the key features of polycystic ovary
syndrome PCOS phenotype), a decrease in blood’s inflammatory
factors such as CRP and IL-6. The administration of curcumin can
lead to improvement in insulin sensitivity, cholesterol levels
and metabolic factors in people with polycystic ovary syndrome
PCOS as well. Curcumin decreased FBS levels and improved
menstruation characteristics (amenorrhea, oligomenorrhea, and
menstrual irregularities) in women with polycystic ovary
syndrome PCOS. After the intervention, amenorrhea and
oligomenorrhea frequency in the curcumin group was significantly
lower than in the placebo group. After 12 weeks of intervention,
the mean serum FBS levels in the curcumin group were
significantly lower than in the placebo group.
Impacts of turmeric and its principal bioactive
curcumin on human health: Pharmaceutical, medicinal, and food
applications: A comprehensive review
Frontiers In Nutrition | February 2023 Recently, the
biological activities of turmeric and curcumin have been
thoroughly investigated. The studies mainly focused on their
antioxidant, antitumor, anti-inflammatory, neuroprotective,
hepatoprotective, and cardioprotective impacts. Over the few
current decades, considerable studies have been conducted on
curcumin due to its beneficial health properties, including
potent antioxidant properties, antimicrobial, anti-inflammation,
anticancer effects, cardio-protectiveness, and hypoglycemic
action. Curcumin has a prolonged history of usage in ancient
medicine, where it was used in various medical treatments as
well as food coloring and spice. Science has advanced over time,
demonstrating curcumin’s many positive benefits for human
health. Technological advances have made it possible to employ
curcumin for various uses in the food and health industries.
According to the results of preclinical and clinical studies
conducted in vitro and in vivo, respectively, curcumin may be
helpful in the prevention and treatment of many diseases,
including cardiovascular diseases, diabetes mellitus, obesity,
allergy, asthma, inflammatory diseases, and neurodegenerative
disorders, e.g., Alzheimer’s, Parkinson’s, multiple sclerosis,
and Huntington’s disease by affecting different molecular
targets. Compared to other medications, curcumin is viewed as a
very cost-effective and safe natural substance that can be used
to prevent and treat many disorders. Black pepper piperine is
one of the most effective boosters of curcumin bioavailability.
The simultaneous administration of curcumin and piperine to
humans or animals boosted the serum levels by more than a
thousandfold. Piperine contained in black pepper can improve the
uptake of curcumin by 2,000% (20 times). The vast metabolism of
turmeric in the hepatic tissues and intestinal walls increased
its bioavailability, which improved through piperine. Taking
these two substances with an oil rich in unsaturated fatty acids
further strengthens this benefit. Zeng et al. examined the
effect of piperine pre-administration on oral curcumin
bioavailability. In this investigation, rats were given 20 mg/kg
piperine first, followed by 200 mg/kg curcumin at intervals of
0.5–8 h after piperine treatment. The pre-treatment with
piperine before curcumin administration significantly increased
curcumin oral bioavailability in all tested rats. Recent
research suggests that oral administration of curcumin and
piperine for symptomatic COVID-19 therapy might dramatically
reduce mortality and morbidity (53). The conjugation between
piperine and curcumin may be a safe and natural option for
preventing post-COVID symptoms.
The Role of Curcumin as an Anti-Aging Compound
Emerging Anti-Aging Strategies
| February 2023 Compounds that may
postpone the onset of age-related symptoms, particularly natural
compounds included in the average diet, are being thoroughly
researched and Curcumin is one among them. It alleviates
age-related symptoms, increases the lifetime of model organisms,
and delays the course of age-related disorders in which cellular
senescence is directly implicated.
Anticancer properties of curcumin-treated
Lactobacillus plantarum against the HT-29 colorectal
adenocarcinoma cells Scientific Reports
| February 2023 When taken orally or
topically, curcumin has a number of anti-inflammatory and
anticancer properties. At both neutral and acidic pH levels,
curcumin possesses potent antioxidant properties. It also
influences cell signaling, enzyme activity, immunomodulation,
angiogenesis, and cell–cell adhesion. Curcumin’s ability to
modulate gene transcription and induce apoptosis in preclinical
models suggests that it may be especially useful for cancer
chemoprevention and chemotherapy in humans. Evidence of
biologically active levels in both animals and humans has been
demonstrated. Oral curcumin has already been studied
extensively, and it appears to have the potential to help people
with invasive or pre-invasive gastrointestinal tract cancers,
particularly those of the colon and rectum. Curcumin may
affect the metabolomics of probiotics in intestinal flora which
could subsequently influence their anticancer properties. The
findings in this study suggest that the metabolomics of
curcumin-treated probiotics may either directly induce enhanced
toxicity against cancer cells or may interact with curcumin
indirectly, amplifying their anticancer effects.
The Therapeutic Role of Curcumin in Inflammation and
Post-Surgical Outcomes Food Reviews
International
| February 2023 Curcumin is a natural
polyphenol derivative that showed to target multiple signaling
molecules at the cellular level and help in supporting health
benefits by acting as a potent anti-inflammatory and antioxidant
compound. It has been shown to be beneficial in the treatment of
inflammatory conditions, metabolic syndrome, wounds,
post-surgical inflammation and outcomes. Curcumin has remarkable
antioxidant and anti-inflammatory properties because it
inhibits inflammatory mediators. Curcuminoids as a preventative
agent against myocardial infarction after coronary artery bypass
grafting (CABG) were evaluated; C-reactive protein, plasma
malondialdehyde, and N-terminal pro-B type natriuretic peptide
levels were all significantly lower in curcumin when compared to
the placebo group. Curcumin by itself has very low
bioavailability due to ineffective absorption, and fast
metabolism and excretion. This issue can be solved by combining
curcumin with piperine (a key active ingredient in black pepper)
to create a curcumin complex that is readily absorbed and
metabolized in the body. Other in-vitro studies have also
demonstrated additional evidence supporting the cardioprotective
effect of curcuminoids is that they inhibit human platelet
activation which eventually lead to decreased occurrence of
myocardial ischemia. Curcumin’s antioxidant properties were
found to reduce adriamycin-induced cardiotoxicity and may help
prevent diabetic cardiovascular complications. Curcumin also has
an anti-thrombotic, anti-proliferative, and anti-inflammatory
properties, and can lower serum cholesterol levels, all of which
may protect against atherosclerosis. In animal models,
curcumin have been shown to reduce the development of cardiac
hypertrophy and heart failure. Curcumin has been shown to have
strong antioxidant and anti-inflammatory effects that could
result in improved post-surgical outcomes. In conclusion, this
review paper shows that curcumin is highly beneficial and has
strong antioxidant and anti-inflammatory effects that could
result in improved post-surgical outcomes. These benefits are
maximized when curcumin is coupled with agents such as piperine,
that significantly increase its bioavailability.
Curcumin Induces Ferroptosis in Follicular Thyroid
Cancer by Upregulating HO-1 Expression
Oxidative Medicine and Cellular Longevity | February 2023
Curcumin has anticancer effects in multiple types of solid
tumors. Research has demonstrated that curcumin has potential
applications in pharmacology and cancer treatment. Curcumin
inhibits cancer cell growth and promotes apoptosis in colorectal
cancer, lung cancer, and prostate cancer. Additionally, numerous
studies have shown that curcumin elevates the HO-1 expression in
a wide range of cancer cells. Tumorigenesis is significantly
inhibited by curcumin. The present study shows that curcumin
inhibits the growth of follicular thyroid cancer by increasing
the HO-1 expression, further activating the ferroptosis pathway.
This study demonstrates that the HO-1-ferroptosis signalling
pathway might play an important role in follicular thyroid
cancer tumorigenesis, and that curcumin inhibits the growth of
follicular thyroid cancer cells by affecting this pathway.
We conclude that curcumin inhibits the tumorigenesis of
follicular thyroid cancer via HO-1-induced activation of the
ferroptosis signalling pathway. Further research is needed to
determine the specific mechanism underlying the effect of
curcumin on follicular thyroid cancer; however, for patients who
cannot tolerate surgery or are difficult to diagnose, it may be
possible to develop a therapeutic pathway towards the remission
of follicular thyroid cancer based on our findings.
Curcumin inhibits pancreatic cancer cell
proliferation Journal of Gastrointestinal
Oncology | January 2023 In hypoxic pancreatic cancer cells,
curcumin can inhibit the HIF-1α-mediated glycolytic pathway by
down-regulating Beclin1 expression, thereby inhibiting cell
proliferation. Furthermore, curcumin reduced cellular adenosine
triphosphate (ATP) production in a dose-dependent manner.
Compared with control pancreatic cancer cells, the expression
levels of GLUT1, HK2, LDHA, and PDK1 gradually decreased with
increasing curcumin concentrations. Curcumin can inhibit the
expression of Beclin1 and HIF-1α in pancreatic cancer cells
under anoxic conditions, thereby affecting the glycolysis
pathway and inhibiting cell proliferation.
Exploring the Neuroprotective Mechanism of Curcumin
Inhibition of Intestinal Inflammation against Parkinson’s
Disease Based on the Gut-Brain Axis
Pharmaceuticals | January 2023 Curcumin is an important
active ingredient of turmeric with a wide range of
pharmacological effects, such as antitumor, antioxidant,
anti-inflammatory, antibacterial, and hypolipidemic properties.
In addition, curcumin promotes Parkinson’s disease treatment
through multiple pathways, including the prevention of reactive
oxygen species (ROS) production, glial cell activation, a-syn
aggregation, neuronal cell apoptosis. Cui et al. suggested
that curcumin may have more important peripheral effects than
direct effects on the central nervous system. Curcumin is known
to improve intestinal barrier function and reduce inflammation.
In a previous study, curcumin was considered neuroprotective in
PD, and this neuroprotective mechanism may act by inhibiting
intestinal inflammation. After treatment with curcumin,
the total movement distance and average speed improved, the
tyrosine hydroxylase (TH) rate in the substantia nigra pars
compacta (SNpc) and striatum were reduced, the pyroptosis of
AIM2 and caspase-1 activations were inhibited, and intestinal
inflammatory factors and intestinal inflammation were reduced.
Curcumin improved gastrointestinal disorders and
gastrointestinal barrier function in the MPTP-induced mice and
reversed MPTP-induced motor dysfunction and dopaminergic neuron
loss in mice. The above effects may be partly dependent on
curcumin activation of the SIRT1/NRF2 pathway in the colon. This
study provides a potential opportunity to develop new preventive
measures and novel therapeutic approaches that could target the
gut–brain axis in the context of PD and provide a new
intervention in the treatment of Parkinson’s disease. In
summary, curcumin can inhibit intestinal pyroptosis through
activation of the SIRT1/NRF2 pathway; reduce intestinal tissue
secretion of IL-1β, IL-6, IL-18, and TNFα; and attenuate the
loss of gastrointestinal barrier proteins ZO-1 and occludin,
elucidating that curcumin is dependent on the gut–brain axis and
thus exerted neuroprotective effects.
Curcumin’s anti-cancerous activity
Williams Cancer Institute | January 2023 For over 5000 years
plants have been used as medicine and therapies and nowadays a
fair amount of modern medicine is directly or indirectly derived
for plants. There are many plant-derived compounds that can
induce apoptosis in cells; these compounds are non-toxic for our
body and are capable of boosting apoptotic pathways. Curcumin
found in turmeric has been found to have many properties
including anti-inflammatory, anti-oxidant, and
anti-carcinogenic. The influence of Curcumin in treating cancer
relies on its effect on cell proliferation, cell survival,
caspase activation, death receptors, mitochondrial, protein
kinase and tumor suppression pathways; so through this
interactions, its able to suppress tumor cells initiation,
progression and metastasis. One of its best qualities is that
curcumin is toxic for cancer yet cytoprotective for normal
cells, making it universal for all kind of cancer cells, proving
positive effects on breast, lung, prostate, pancreatic, oral,
colorectal, multiple myeloma and head and neck squamous cell
carcinoma Also, it’s been shown that people from southwest Asia
who regularly consume turmeric in their diet, have the lowest
incidence of any type of cancer. Despite its actual mechanism
against cancer is still unknown so far it has demonstrated to be
a good, natural and safe adjuvant in cancer treatment.
Attenuation of Inflammatory Responses in Breast and
Ovarian Cancer Cells by a Novel Chalcone Derivative and Its
Increased Potency by Curcumin Mediators of
Inflammation | January 2023 Curcumin, is extensively studied
for its various pharmacological effects, including anticancer
properties. Curcumin has shown promising results in treating
cancer, both alone and in combination with other
chemotherapeutic agents. It exerts anticancer effects, mainly by
modulating various signaling pathways and transcription factors.
Curcumin is a well-known natural product with numerous
pharmacological effects, especially in cancer. It has been
shown in recent studies that curcumin inhibits cell
proliferation, promotes apoptosis, suppresses chemotherapeutic
resistance, and exerts antimetastatic effects in the treatment
of both breast and ovarian cancers, either alone or combined
with other chemotherapeutic agents. In conclusion, our findings
suggest that MPP, a novel synthetic derivative of chalcone,
alone or in combination with curcumin, could serve as an
effective anti-inflammatory and cytotoxic treatment for
combating breast and ovarian cancer, mediated by the inhibitory
effect of this combination on NF-κB activity and its downstream
genes. All the effects of MPP were enhanced by the addition of
curcumin. MPP, especially when combined with curcumin, caused a
remarkable increase in the concentration of IκB. MPP and
its coadministration with curcumin effectively reduced the
activity of the NF-κB signaling pathway, leading to a reduced
inflammatory response in the environment of cancer cells.
Curcumin for the treatment of COVID-19 patients: A
meta-analysis of randomized controlled trials
Phytotherapy Research | January 2023 Curcumin is a low-cost
and easily accessible therapeutic option for COVID-19 patients.
Curcumin reduced the risk of all-cause mortality (RR 0.38; 95%
CI: 0.20–0.72; moderate certainty of evidence), and patients
with no recovery status (RR 0.54; 95% CI: 0.42–0.70; moderate
certainty of evidence). The results of subgroup analysis
suggested a higher benefit with early administration of curcumin
(within 5 days of onset of symptoms) and with the use of
combination regimens. Curcumin is likely to be of benefit in
mild-to-moderate COVID-19 patients.
Inhibiting
proliferation and migration in cervical cancer by curcumin and
resveratrol
Natural Product Research | January 2023 Functional
experiments indicated that curcumin displayed stronger
inhibitory activity on the proliferation of cervical cancer HeLa
cells. Curcumin exerted its anti-cervical cancer effect by
regulating cell cycle mitosis, whereas resveratrol affected
adhesion. Furthermore, the target genes were verified by
molecular docking, qRT-PCR, and Western blot, the results
revealed that curcumin and resveratrol significantly decreased
the expression of CHEK1 and MAPK3, respectively. In conclusion,
curcumin inhibited the proliferation of cervical cancer HeLa
cells by specifically targeting CHEK1, while resveratrol
specifically targeted MAPK3 to supress migration, and the
combination of them can synergistically restrain the
proliferation and migration of cervical cancer cells.
Curcumin treatment suppresses cachexia-associated
adipose wasting in mice by blocking the cAMP/PKA/CREB signaling
pathway Phytomedicine | January 2023
Curcumin significantly reduced serum levels of free fatty acids
and increased triglyceride levels. In addition, curcumin
significantly inhibited PKA and CREB activation in the adipose
tissue of cancer cachectic mice. Curcumin also ameliorated
CL316243-induced adipose atrophy and inhibited hormone-mediated
PKA and CREB activation in mice. Moreover, the lipid droplet
degradation induced by C26 tumor cell conditioned medium in
mature 3T3-L1 adipocytes was ameliorated by curcumin treatment.
Curcumin also improved the lipid droplet degradation of mature
3T3-L1 adipocytes induced by CL316243. Curcumin might be
expected to be a therapeutic supplement for cancer cachexia
patients, primarily through inhibiting adipose tissue loss via
the cAMP/PKA/CREB signaling pathway. Curcumin alleviated cancer
cachexia-associated adipocyte atrophy and lipid degradation. The
protective effects of curcumin on cachectic fat loss are
mediated by the cAMP/PKA/CREB signaling pathway.
Curcumin suppresses cell proliferation and reduces
cholesterol absorption
Lipids in Health and Disease
| January 2023 Curcumin is a bioactive dietary
polyphenol of turmeric with various biological activities
against several cancers. Several studies have demonstrated the
protective effects of Curcumin against varied cancers, including
lung cancer, breast cancer, gastric cancer, colorectal cancer
and so on. In addition, an epidemiological analysis showed an
association between dietary consumption of Curcumin and
decreased incidence of colorectal cancer in the Indian
population. Several potential mechanisms of curcumin-related
anti-cancer effects in colorectal cancer have been identified,
such as mechanisms involving DNA damage, cell cycle arrest,
apoptosis, colorectal cancer angiogenesis, epidermal growth
factor receptor signaling pathway, and tumor immunomodulation.
Furthermore, Zou J. et al found that curcumin could reduce
intestinal cholesterol absorption by 51% in mice. Studies have
demonstrated the potential anti-tumor effects of curcumin on
CRC. In summary, the present study demonstrates that curcumin
suppresses the proliferation of Caco-2 cells and reduces
cholesterol absorption through activate the TRPA1 channel.
Furthermore, the potential antitumor effect of curcumin in a
high-lipid environment was determined. Curcumin is a bioactive
dietary polyphenol that exhibits anticancer and lipid-lowering
effects in vitro. Curcumin could serve as a natural active
ingredient to be used in the primary prevention of colorectal
cancer in clinical practice.
Curcumin enhances the anti-cancer efficacy of
paclitaxel in ovarian cancer Frontiers | January 2023 Curcumin
has been shown to synergistically enhance the therapeutic
effects of multiple chemotherapeutic agents, but the potential
involvement of curcumin in ovarian cancer is largely unknown.
Curcumin and paclitaxel synergistically inhibited proliferation
and promoted apoptosis in ovarian cancer cells. Furthermore,
curcumin and paclitaxel combination resulted in decreased
miR-9-5p expression and increased BRCA1 expression.
Functionally, miR-9-5p overexpression counteracted the
synergistic effect of curcumin and paclitaxel on cell
proliferation and apoptosis by targeting BRCA1. Meanwhile, in
vivo experiments revealed that curcumin and paclitaxel
combination dramatically suppressed the growth of transplanted
tumors, while miR-9-5p mimics eliminated the growth inhibition
of xenografts induced by the combined treatment. Conclusion:
Curcumin enhanced the anti-cancer efficacy of paclitaxel in
ovarian cancer by regulating the miR-9-5p/BRCA1 axis. These
findings provide strong evidence for clinical investigation of
curcumin and paclitaxel combination as a novel strategy for
ovarian cancer patients.
MiR-125b-5p is targeted by curcumin to regulate the
cellular antioxidant capacity Free Radical
Research | January 2023 As a natural polyphenolic food
supplement and the principal curcuminoid in turmeric, curcumin
shows antioxidant, anti-inflammatory, and antitumor activities.
Cellular antioxidant capacity induced by curcumin extract was
inhibited by miR-125b-5p overexpression. Thus, curcumin may
exhibit antioxidant effects by repressing miR-125b-5p
expression, which provides new insights into the molecular
antioxidant mechanism of curcumin.
Curcumin Stimulates UCP1-independent Thermogenesis
in 3T3-L1 White Adipocytes but Suppresses in C2C12 Muscle Cells
Biotechnology and Bioprocess Engineering | January
2023 The anti-obesity effect of curcumin involves mainly two
interacting parts, one mediated via β3-AR and cAMP
(UCP1-dependent) and the other via α1-AR and increase in
cytosolic Ca2+ levels (UCP1-independent) in beige fat but not in
muscle cells.
Curcumin
Reduces Pathological Endoplasmic Reticulum Stress
International Journal of Molecular Sciences |
January 2023 Several published studies show that curcumin
treatment reduces ER stress in a range of conditions. We can
identify a “natural” chemical, curcumin, which is able to reduce
pathological ER stress in a cell model of EDM5 by promoting the
proteasomal degradation mutant matrilin-3. Therefore, this is an
important in vitro study in which we describe, for the first
time, the success of a naturally occurring chemical as a
potential treatment for this currently incurable rare skeletal
disease. This is an important and exciting area of research that
will have significant clinical impact on a range of human
diseases including the rare skeletal disease, EDM5.
The
Effects of Curcumin on Inflammasome: Latest Update
Molecules | January 2023 Curcumin, a natural
monomer extracted from plants, has gained popularity in recent
decades due to its therapeutic benefits in a wide range of human
pathological conditions. The medicinal plant Curcuma longa
Linn, a perennial herb of the Zingiberaceae family known as
“golden spice” for its broad spectrum of pharmacological
properties, contains curcumin as one of its most active
constituents. In addition, the chemical structure of curcumin
makes it an excellent scavenger of reactive oxygen and nitrogen
species (ROS and RNS, respectively). As a result, curcumin can
attenuate or prevent exercise-induced oxidative stress and
inflammation. Curcumin activates the Nrf2 pathway, which is
important for the activation of antioxidant enzymes . Curcumin
is well known to have anti-inflammatory effects, and its role in
modulating neuroinflammation in several neurological disorders
has been extensively described. Taken together, in vitro, in
vivo, and clinical studies confirmed curcumin’s promising
effects for attenuating inflammation and oxidative stress,
alleviating the patient’s pain, protecting joints from damage,
and improving the quality of life of rheumatoid arthritis
patients without side effects. Curcumin encapsulation in
nanoparticles or in combination with MSCs showed an effective
and promising strategy for increasing curcumin bioavailability
and efficacy in rheumatoid arthritis. In addition, new curcumin
formulations and administration routes (such as oral and
topical) have been proposed as effective strategy for treating
rheumatoid arthritis. In this review, we have focused on the
therapeutic effects of curcumin administration in various
inflammatory diseases, focusing on its functional mechanisms in
preventing activation of the NLRP3 inflammasome. Future research
will address the clinical application of curcumin to treat
diseases in which the inflammasome is activated.
Review of Curcumin and Its Different Formulations:
Pharmacokinetics, Pharmacodynamics and
Pharmacokinetic-Pharmacodynamic Interactions
OBM Integrative and Complementary Medicine | January 2023
Curcumin has many pharmacological activities, such as
antioxidant, anti-inflammatory, antibacterial, antiviral,
antidiabetic, anticancer, and immunomodulatory activities,
against neurological disorders as well as digestive disorders.
Curcumin acts as an antioxidant by potentially scavenging
various free radicals, such as reactive oxygen and nitrogen
species, and inhibiting lipoxygenase/cyclooxygenase and xanthine
dehydrogenase/oxidase, enzymes that are thought to generate
reactive oxygen species. In addition, it can act directly by
upregulating the antioxidant defense enzymes, such as superoxide
dismutase and glutathione peroxidase. Despite possessing
potential pharmacological activity, as well as safety at high
doses (12 g/day), curcumin therapeutics still face low
bioavailability. Piperine increased the bioavailability of
curcumin by 154%. Curcumin combined with piperine exhibited
higher intestinal absorption (78%). When co-administered with
piperine, the half-life of curcumin was increased from 12.8h to
28.9h. Co-administration of piperine (20 mg/kg) and curcumin (2
mg/kg) increased the plasma concentration of curcumin in a short
time, i.e. within 1-2h, peak time was increased, elimination
half-life decreased, and clearance decreased. In humans, even
with a 2g load of curcumin, the serum level was undetectable. A
higher extent of absorption and higher bioavailability of
curcumin (2000%) was observed in humans using 20mg piperine. The
pharmacological activities of curcumin and its related
formulations and products have been reviewed in a few targeted
disease pathologies of national concern, such as cancer,
gastroduodenal disorder, immunodeficiency, liver disease,
ophthalmology, diabetes and osteoarthritis among other metabolic
diseases, and microbial and viral infections.
Curcumin Induces Ferroptosis in Follicular Thyroid
Cancer by Upregulating HO-1 Expression
Oxidative Medicine and Cellular Longevity | January 2023
Research has demonstrated that curcumin has potential
applications in pharmacology and cancer treatment. Curcumin
inhibits cancer cell growth and promotes apoptosis in colorectal
cancer, lung cancer, and prostate cancer. Additionally, numerous
studies have shown that curcumin elevates the HO-1 expression in
a wide range of cancer cells. The present study shows that
curcumin inhibits the growth of FTC by increasing the HO-1
expression, further activating the ferroptosis pathway. This
study demonstrates that the HO-1-ferroptosis signalling pathway
might play an important role in FTC tumorigenesis, and that
curcumin inhibits the growth of FTC cells by affecting this
pathway. We conclude that curcumin inhibits the tumorigenesis of
FTC via HO-1-induced activation of the ferroptosis signalling
pathway. Further research is needed to determine the specific
mechanism underlying the effect of curcumin on FTC; however, for
patients who cannot tolerate surgery or are difficult to
diagnose, it may be possible to develop a therapeutic pathway
towards the remission of FTC based on our findings.
Curcumin supplementation contributes to relieving
anthropometric and glycemic indices, as an adjunct therapy: A
meta-research review of meta-analyses
Journal of Functional Foods Volume | January 2023 Curcumin
supplementation can improve anthropometric and glycemic
parameters in a time- and dose- dependent manner.
Administered dose of > 1 g/day of curcumin has the most
beneficial effect on anthropometric and glycemic indices. Longer
durations of supplementation (>10-week) are needed to have the
decreasing impact on HOMA-IR and HbA1c. Curcumin supplementation
can be administered as the adjuvant therapy in managing
hyperglycemia, insulin resistance, and obesity. The significant
effects of Curcuma longa are primarily due to curcumin (Pulido-Moran
et al., 2016). Some beneficial effects of curcumin have
been revealed, including anti-diabetic properties, antioxidant
properties, and anti-inflammatory properties (Kalpana and Menon,
2004, Tsuda, 2018). Curcumin can have beneficial roles in some
chronic illnesses, e.g., coronary artery disease,
atherosclerosis, rheumatoid arthritis, obesity, and T2DM
(Aggarwal and Harikumar, 2009, Karimi et al., 2022). The
beneficial role of curcumin on glycemic control is due to its
inhibitory effect on hepatic gluconeogenesis, glycogenesis, and
hyperglycemia-mediated inflammation development (Ghorbani et
al., 2014). Besides, it has been reported that curcumin can
decrease angiogenesis in adipose tissue (Pivari et al., 2019,
Seo et al., 2008), decrease pre-adipocyte differentiation by
increasing resting energy expenditure by activating peroxisome
proliferator- activated receptor gamma (PPAR-γ((İçer and Tek,
2021, Seo et al., 2008), reduce adipogenic genes expression (Kim
et al., 2011, Lee et al., 2009), and inhibit cortisol-mediated
central obesity (Hu et al., 2013). The beneficial role of
curcumin on glycemic control may be stemmed from its inhibitory
effect on the phosphorylation kinase enzyme involved in glycogen
storage mobilization (Razavi et al., 2021). It has been
demonstrated that curcumin can substantially lower FBS and HbA1c
levels (Tabrizi et al., 2018; Wei et al., 2019). Curcumin can be
effective in different health conditions and age groups. With
moderate reliability, curcumin supplementation can be
administered as the adjuvant therapy in managing hyperglycemia,
insulin resistance, and obesity.
Fluoxetine and Curcumin Prevent the Alterations in
Locomotor and Exploratory Activities and Social Interaction
Elicited by Immunoinflammatory Activation in Zebrafish:
Involvement of BDNF and Proinflammatory Cytokines
ACS Chemical Neuroscience | January 2023 The increase in
proinflammatory cytokine expression causes behavioral changes
consistent with sickness behavior, and this led to the
suggestion that depression might be a psychoneuroimmunological
phenomenon. Fluoxetine and curcumin prevented the sickness
behavior induced by A. hydrophila and the increased expression
of proinflammatory cytokines. Our results point to the potential
of zebrafish as a translational model in studies related to
neuroinflammation and demonstrate for the first time the effects
of fluoxetine and curcumin on zebrafish sickness behavior.
Curcumin combined with verapamil improve
cardiovascular phenotype of a Williams-Beuren Syndrome mice
model reducing oxidative stress bioRxiv |
January 2023 Curcumin is a natural yellow pigment, which has
attracted much attention in recent years owing to its wide
spectrum of biological activities, including antioxidant, anti-
inflammatory, anti-tumor, or anti-microbial activities, (Llano
et al., 2019; Bozkurt et al., 2022). Besides, curcumin improved
cardiovascular structure and function, especially with the
normalization of systolic blood pressure and collagen deposition
in rats with diet-induced metabolic syndrome (du Preez et al.,
2019). In addition, curcumin has previously shown cardiac
protection in front of palmitate and high fat diet mediated the
activation of the nuclear factor erythroid 2 (NRF2) (Zeng et
al., 2015). A combination of curcumin and verapamil
significantly ameliorates the cardiovascular phenotype of a
mouse model for WBS. Its efficiency is achieved through
reduction of oxidative stress levels evidenced by the reduction
of XOR protein levels and induction of NRF2 pathway, both in the
aortic wall and LV-myocardium. Verapamil is already approved for
human use, while curcumin is a natural safe product. We here
shown that their combination deserves further evaluation as
potential therapeutic agent to prevent the severe cardiovascular
injuries occurring in human patients with WBS.
Curcumin suppresses lung cancer progression via
circRUNX1 mediated miR-760/RAB3D axis
Thoracic Cancer | December 2022 Curcumin has
antioxidant, antibacterial, anti-inflammatory, and anticancer
pharmacological effects, and it therefore has the potential to
become an effective drug for treating arthritis, cardiovascular
disease and cancer. Studies have reported that curcumin
exerts its anticancer effect by inhibiting cancer cell
proliferation, metastasis, and promoting apoptosis, including
lung cancer. Curcumin, as a natural phytochemical, is attracting
more and more attention. The anticancer role of curcumin has
previously been confirmed in hepatocellular, breast and
pancreatic cancers. Here, we reveal the anticancer effect of
curcumin in lung cancer progression. Curcumin hindered
proliferation, metastasis, increased the apoptosis of lung
cancer cells, and restrained lung cancer tumor growth. Our
results are consistent with previous studies, which indicate
that curcumin is an effective substance to suppress lung cancer
progression. In conclusion, our study showed that curcumin plays
an anticancer role in the progression of lung cancer, which is
mainly realized by circRUNX1/miR-760/RAB3D axis. Our study
revealed for the first time that curcumin inhibits lung cancer
progression by regulating the circRNA network, which not only
provides more evidence for the anticancer role of curcumin, but
also provides a new molecular target for lung cancer treatment.
Childhood obesity and curcumin: a possible effective
anti-obesity adjunct Advances in Obesity,
Weight Management & Control | December 2022 Curcumin, an
important compound present in the Curcuma longa L.
rhizome is a lipophilic molecule that can rapidly permeate cell
membranes to exert its effect. Other intervention studies that
have examined the impact of dietary polyphenols including
curcumin have further shown its ability to improve insulin
resistance, as well as obesity-associated low grade inflammatory
responses, a main determinant of the pathology of multiple
chronic health conditions, and possibly caused in part by an
inadequate nutrient intake that induces alterations in the lipid
content of adipose tissue and activation of immune and adipose
cells and others that foster local and systemic inflammation.
Additional recent evidence points not only to the
anti-inflammatory effects of curcumin in this regard, but also
its metabolic effects that can help to relieve obesity, as well
as obesity-associated chronic health conditions. Moreover,
curcumin appears to have pharmacological properties that
objectively lower body weight, fat mass and triglyceride levels,
while enhancing energy expenditure, fat utilization, and glucose
hemostasis. Unsurprisingly, among the many beneficial health
affirming impacts reported for curcumin, research specifically
focused on obesity and the metabolic-preventing/suppressing
aspects of curcumin is growing. Curcumin in its various forms
where present or administered in adequate amounts is likely to
either help initiate or offset excess weight, and promote weight
loss, more often than not, and via well defined cellular
pathways and molecular mechanisms of action, that support its
apparent ameliorating effect on inflammation and diabetes
extent, especially in cases with early onset obesity, or where
losing weight via traditional interventions may be a perpetual
‘losing’ battle. Among the potential mechanisms for offsetting
some degree of obesity, and its ramifications, the role of the
spice known as curcumin currently appears to exhibit very
favorable promise based on its ability to interact at the
cellular and molecular level, and attested to in most emergent
cellular, preclinical and clinical data sets that could be
adapted to support the idea of personalized and precision
medicine.
Curcumin
inhibits pancreatic cancer cell proliferation by regulating
Beclin1 expression and inhibiting the hypoxia-inducible
factor-1α- mediated glycolytic pathway
Journal of Gastrointestinal Oncology | December 2022
Curcumin has a wide range of antioxidant and anti-inflammatory
activities, as well as inhibition of the mitochondrial cascade.
Additionally, it has shown significant antitumor activity. In
conclusion, in hypoxic pancreatic cancer cells, curcumin can
inhibit the HIF-1α-mediated glycolytic pathway by
down-regulating Beclin1 expression, thereby inhibiting cell
proliferation.
Micronutrient Supplementation to Reduce
Cardiovascular Risk Journal of the American
College of Cardiology | December 2022 Curcumin, flavanol, genistein, and
quercetin showed moderate- to high-quality evidence for reducing
CVD risk factors. Supplementation of some but not all
micronutrients may benefit cardiometabolic health. This study
highlights the importance of micronutrient diversity and the
balance of benefits and risks to promote and maintain
cardiovascular health in diverse populations.
Not all micronutrients are created equal: Study
identifies some supplements that benefit cardiovascular health
Medical Express | December 2022 A comprehensive and systematic
approach to evaluate all the publicly available and accessible
studies reporting all micronutrients, including phytochemicals
and antioxidant supplements and their effects on cardiovascular
risk factors as well as multiple cardiovascular diseases. The
researchers looked at randomized, controlled intervention trials
evaluating 27 different types of antioxidant supplements. They
found strong evidence that several offered cardiovascular
benefit. Curcumin, flavanol, genistein and quercetin showed
evidence of reducing cardiovascular risk.
Curcumin Inhibits Proliferation of Renal Cell
Carcinoma in vitro
and in vivo
by Regulating miR-148/ADAMTS18 through Suppressing Autophagy
Journal of Integrative Medicine | December 2022 Curcumin can
inhibit the proliferation of renal cell carcinoma by regulating
the miR-148/ ADAMTS18 axis through the suppression of autophagy
in vitro and in vivo. There may exist a positive feedback loop
between miR-148 and ADAMTS18 gene in RCC.
Curcumin Regulates Gut Microbiota and Exerts a
Neuroprotective Effect in the MPTP Model of Parkinson's Disease
Evidence-Based Complementary and Alternative Medicine | December
2022 All curcumin groups improved cell wrinkling and vacuolar
degeneration, increased the number of TH positives, improved
cell survival, and the higher the dose of curcumin, the better
the effect. The relative abundance of Patescibacteria,
Enterobacteriaceae, Enterococcaceae all decreased in all
curcumin groups. In addition, the Kyoto Encyclopedia of Genes
and Genomes pathways showed a reduction in the superpathway of
N-acetylneuraminate degradation after medium and high-dose
curcumin administration. Curcumin regulates gut microbiota and
exerts a neuroprotective effect in the MPTP mice model. This
preliminary study demonstrates the therapeutic potential of
curcumin for Parkinson's disease, providing clues for
microbially targeted therapies for Parkinson's disease.
Curcumin, a polyphenol extracted from the rhizomes of
Curcuma longa, is converted into biologically active
metabolites in the intestine by microbial digestion. Nowadays,
it has been shown to have multiple effects such as
anti-inflammatory, antioxidant, anticancer, and mitochondrial
protection. The bidirectional interplay between curcumin and gut
microbes has been demonstrated, as curcumin is not only
metabolized by the enzymes of the gut microbes to produce active
metabolites but it also strengthens the intestinal barrier and
changes the composition of the gut microbes. Thus, curcumin can
exert a wide range of pharmacological effects through the
“microbe-gut-brain axis” and can be used to treat many chronic
diseases. Curcumin has shown an extremely high therapeutic
potential in Parkinson's Disease. In animal models, dyskinesia
can be improved after the use of curcumin. Many studies have
also confirmed that curcumin increased the survival of tyrosine
hydroxylase striatal fibers and nigrostriatal dense part neurons
in rat PD model induced by 6-hydroxydopamine (6-OHDA),
exhibiting increased dopamine levels. Concomitantly, curcumin
can exert anti-inflammatory effects by inhibiting
microglia-mediated neuroinflammation and reducing interleukin-2,
chemokines, and cyclooxygenase-2. Curcumin has also been shown
to increase the electrical activity of hippocampal neurons in
rotenone-induced Parkinson's Disease model rats and regulate the
activity of mitochondrial enzyme complex. In addition, a recent
clinical study found that curcumin improved motor and nonmotor
symptoms and reduced the aggregation of phosphorylated α-Syn in
skin biopsies in Parkinson's Disease patients. Our study shows
that curcumin can effectively regulate the changes of gut
microbiota, improve the dysfunction of MPTP mice, reduce the
neurotoxicity of MPTP in Parkinson's Disease mice, and protect
DA neurons, and there is some correlation with the dose. This
preliminary study demonstrates the therapeutic potential of
curcumin for Parkinson's Disease, providing clues for
microbially targeted therapies for Parkinson's Disease.
Curcumin in Ulcerative Colitis
Encyclopedia.pub | December 2022 The significant
anti-inflammatory properties of curcumin, being described over
the years have attracted a lot of researchers’ interest,
especially in the context of treating diseases with a chronic
inflammation basis. In many studies it has been shown that
curcumin inhibits NF-κB expression by blocking IkappaB (IκB)
kinase, that leads to the prevention of cytokine-mediated
phosphorylation and the degradation of IκB, which is an NF-κB
inhibitor. Furthermore, it was also reported that curcumin
inhibited the activity of proinflammatory proteins (e.g.,
activated protein-1, peroxisome proliferator-activated receptor
gamma, transcription activators, the expression of β -catenin).
As oral supplementation with curcumin leads to its high
concentration in the gastrointestinal tract, studies have slowly
focused on its impact on the intestinal microbiota. Via this
mechanism, the problem of low systemic curcumin bioavailability
probably is not a significant issue within the gastrointestinal
tract, and curcumin may have a hypothetical beneficial influence
on the gut microbiome. A bidirectional interaction exists
between curcumin and gut microbiota. Gut microbiota are actively
involved in curcumin metabolism, which lead to curcumin
biotransformation (demethylation, hydroxylation, demethoxylation)
and the production of metabolites. Curcumin supplementation is
effective in promoting the growth of beneficial bacterial
strains, improving intestinal barrier functions, and
counteracting the expression of pro-inflammatory mediators.
Peterson et al., in a double-blind, randomized,
placebo-controlled pilot study with 30 healthy subjects,
assessed changes in the gut microbiota using 16S rDNA sequencing
after oral supplementation with turmeric 6000 mg with extract of
piperine, curcumin 6000 mg with Bioperine (black pepper extract)
tablets, or placebo, at baseline and after 4 and 8 weeks. They
found that both turmeric and curcumin in a highly similar manner
altered the gut microbiota. Participants who took turmeric
supplementation displayed a 7% increase in observed microbial
species post-treatment, and curcumin-treated subjects displayed
an average increase of 69% in detected bacterial species.
Protective effect of curcumin on the kidney of
diclofenac sodium-challenged mice: apoptotic, redox potential
and histopathological outcomes The Journal
of Basic and Applied Zoology | December 2022 Curcumin
can be used as a promising natural phytochemical in rescuing
chemotherapy-associated renal dysfunction owing to its redox
stabilizing and cytoprotective nature. In folk medicine,
curcumin is a well-known therapeutic approach for numerous
respiratory and gastrointestinal ailments (Araujo & Leon, 2001).
According to Oriental beliefs, it has habitually been used in
fighting abnormalities linked to inflammatory and peroxidative
injury (Trujillo et al., 2013). Most of the biological actions
of Curcuma longa L. are attributed to curcumin, which
is suggested to be a top-ranked alternative in protecting
against chemotherapy-associated disturbances as it reduces the
production of apoptotic mediators and free radicals. The
anti-apoptotic ability of curcumin is mediated by activating the
DNA repair process (Chen et al., 2017), down-regulating the
transcript levels of pro-apoptotic mediators, up-regulating
those of anti-apoptotic mediators and inducing cytoprotective
proteins (Ben Yehuda Dai et al., 2016; Greenwald et al., 2017).
Neutralization of reactive oxygen species, up-regulation of
enzymatic antioxidants expression and stimulation of the
production of non-enzymatic ones (Barzegar & Moosavi-Movahedi,
2011; Lavoie et al., 2009) reflect the dual functional
antioxidant role of curcumin. The above-mentioned multifaceted
properties of curcumin offer a solid intellectuality for
interfering with the different toxicological targets of DS.
Curcumin succeeded in restoring the typical histomorphometric
features and reducing the apoptosis in the kidney. Curcumin
might exert its renoprotective action through its cytoprotective,
anti-apoptotic and antioxidant characteristics. The findings of
this study shed light on using natural phytochemicals to
alleviate the adverse influences of chemotherapies. . These
outcomes are of utmost significance in opening windows toward
incorporating curcumin in fighting the DS-related defects and
touching a new ground for exploring its usefulness in combating
the other dangerous effects of DS.
Beneficial effects of curcumin in the diabetic rat
ovary: a stereological and biochemical study
Histochemistry and Cell Biology | December 2022 Curcumin
treatment had a protective effect on the number of primordial
follicles in the DC2 group and on antral follicle numbers in the
DC3 group. Curcumin also exhibited positive effects on CAT
activity and SOD levels, blood glucose levels, and corpus
luteum, connective tissue, and blood vessel volumes in the DC2
and DC3 groups. Curcumin also ameliorated FSH levels in the DC1
and DC3 groups (p < 0.01). These findings suggest that curcumin
exhibits protective effects on ovarian structures and
folliculogenesis, especially when used concurrently with the
development of diabetes or in later stages of the disease.
Old but Fancy: Curcumin in Ulcerative Colitis—Current Overview
Nutrients | December 2022 Over the last
few years curcumin, a natural polyphenol belonging to the
curcuminoid family (compounds derived from Curcuma longa L.
[turmeric root]), is of greater interest in the context of
managing UC. It seems that curcumin is a promising natural
compound due to its widely described multi-beneficial effects on
microbiota alteration and antioxidative, antitumor and—the most
relevant—anti-inflammatory properties. Curcumin, also known as
the ‘golden spice of India’, has been used for thousands of
years as an essential medicinal, herbal ingredient that exhibits
anti-inflammatory, antioxidant, or antimicrobial properties,
mainly. It is also well-known in Chinese traditional medicine.
Since 2020, the interest in curcumin for treating UC has
increased noticeably, as evidenced by the increase in published
systematic reviews. Searching via PubMed the descriptors
“curcumin and ulcerative colitis” yielded sixteen systematic
reviews and/or meta-analyses since 2012, where nine of them have
been published from 2020 to the present. For some individuals
affected by UC, there seems to be a real need to identify
curcumin’s role as a supplement in safe, bioavailable, tolerated
doses, and to incorporate it into routine clinical practice for
better clinical outcomes and improvement of the quality of life
of patients.
New Insights into Dose-Dependent Effects of Curcumin
on ARPE-19 Cells International Journal of
Molecular Sciences | December 2022 Curcumin is a natural and
biologically-active molecule that has been largely studied
because of its versatility; indeed, there is a huge number of
studies based on the use of curcumin in different pathological
contexts, including ocular diseases. This compound has been
shown to elicit antioxidant, anti-inflammatory, and
anti-angiogenic effects in various cell systems. Curcumin is
particularly important because of its versatility. Curcumin is
the main curcuminoid extracted from the rhizome of Curcuma
longa. Curcumin is considered a pleiotropic compound
because of its ability to interact with many cellular components
and influence a high number of cellular mechanisms. Altogether,
our findings show new dose-dependent mechanisms of action of
curcumin that suggest a wide therapeutic application in ocular
diseases with different pathogenesis (i.e., proliferative
vitreoretinopathy or Age-Related Macular Degeneration). This
interpretation is in accordance with previous evidence about the
cytotoxic effects of curcumin in particular conditions and
contributes to underlining new insights into the effects of this
very useful compound. Taken together our results agree with the
high versatility of Curcumin for application in ophthalmic
diseases. Administration of high concentrations of curcumin may
be recommended to limit the progression of the disease. By
contrast, a lower dosage of Cur should be used for ocular
pathologies characterized by RPE degeneration, such as
Age-related macular degeneration, to promote RPE health and
survival. We also showed new dose-dependent effects of curcumin,
highlighting mechanisms by which curcumin acts on RPE cells
which lays the foundation for further studies in the field.
Curcumin:
A Novel Way to Improve Quality of Life for Colorectal Cancer
Patients? International Journal of
Molecular Sciences | December 2022 Several preclinical
studies have demonstrated that curcumin acts through multiple
cellular pathways and possesses both anti-cancer properties
against CRC and the capacity to mitigate chemotherapy-related
side effects and overcome drug resistance. In this review
article, we suggest that the addition of curcumin to the
standard chemotherapeutic treatment for metastatic CRC could
reduce associated side-effects and overcome chemotherapy
resistance, thereby improving patient QoL. For many years,
curcumin (diferuloylmethane)—the “golden spice”—has been widely
studied because of its pleiotropic effects in cancer. Curcumin,
a hydrophobic polyphenol, is derived from the rhizome of the
herb Curcuma longa and constitutes the major curcuminoid in the
spice turmeric (77% curcumin, 17% demethoxycurcumin, 3% bis-demethoxycurcumin).
Curcumin is “generally recognized as safe” (GRAS) as a dietary
supplement by the U.S Food and Drug Administration (FDA) and the
European Food Safety Authority (EFSA) and has been catalogued
with the E100 code of the European Union. One of the clinical
benefits of curcumin is the improvement of Quality of Life in
several health conditions, including cancer. Curcumin is a
pleiotropic agent that acts through multiple cellular pathways
and has been shown to possess anti-cancer properties against
Colorectal Cancer in vitro and in vivo. Many of its anti-cancer
properties have been attributed to its role as an
anti-inflammatory and antioxidant, as well as to its ability to
modulate the cell cycle and the pathways involved in
proliferation, apoptosis, migration, invasion, angiogenesis, and
metastasis, which are typically targeted by the drugs used to
treat Colorectal Cancer. Mechanistically, curcumin modulates
several Colorectal Cancer molecular targets at the same
time—either by altering their gene expression, activation, or
signaling pathways, or by direct interaction. Importantly, in
addition to its well-known anti-cancer properties, curcumin can
also alleviate some of the chemotherapy-related side effects.
For example, curcumin attenuates the liver injury induced by
oxaliplatin through activation of the nuclear factor-erythroid
2-related factor 2 (Nrf2) signaling, a key regulator pathway of
cellular defense against oxidative and electrophilic stresses,
as well as the nerve damage and the oxidative damage to
mitochondria caused by oxaliplatin. In fact, curcumin has been
shown to not only hinder mitochondrial damage but also to
protect mitochondria and induce activity of mitochondrial
complex enzymes. Interestingly, similar effects of curcumin on
cisplatin-related toxicity have been observed in several tumor
types. Additionally, curcumin protects against irinotecan-induced
intestinal injury by inhibiting nuclear factor kappa B (NF-κB).
Recently, it has been shown that curcumin attenuates
bevacizumab-associated cardiotoxicity by suppressing oxidative
stress and preventing mitochondrial dysfunction in heart
mitochondria. In a study of curcumin’s effects in cancer
patients, Belcaro and colleagues looked at the side effects of
chemotherapy in several tumor types, including colon, ovarian,
lung, liver, kidney, and stomach cancers. Of 80 patients treated
with chemotherapy, 40 simultaneously received 500 mg of
curcumin. Chemotherapy-related nausea, diarrhea, constipation,
weight loss, neutropenia, and cardiotoxicity were significantly
lower in the patients receiving curcumin than in the control
group. Moreover, patients receiving curcumin also required fewer
medications for treating these side effects. In the same vein,
turmeric supplementation for 21 days resulted in a clinically
relevant and statistically significant improvement in global
health status, symptom scores (fatigue, nausea, vomiting, pain,
appetite loss, insomnia), and hematological parameters of breast
cancer patients treated with paclitaxel. Taken together, these
findings lead us to suggest that the addition of curcumin to the
standard treatment of Colorectal Cancer could not only attenuate
chemotherapy-associated side effects but also improve the QoL of
patients. Most clinical data on curcumin come from early phase
clinical trials, with results showing that oral curcumin can
achieve efficacious levels in the colon with negligible
distribution outside the gut. Moreover, curcumin was shown to be
safe in advanced Colorectal Cancer patients when administered
for up to four months. In addition, a study by James and
colleagues found that curcumin at doses up to 2 gms daily was
highly tolerable when added to a FOLFOX regimen in Colorectal
Cancer patients with liver metastases. More recently, the same
group performed a phase IIa randomized trial of first-line
treatment for mCRC patients comparing FOLFOX +/−bevacizumab with
the same regimen plus curcumin 2 gms/day (CUFOX) in mCRC
patients. One of the most commonly used herbal supplements is
curcumin, which has been extensively studied in cancer
prevention and treatment. In fact, a plethora of preclinical
studies have demonstrated the anti-cancer properties of curcumin
as well as its role as a chemosensitizer agent. Several
preclinical studies have demonstrated that the addition of
curcumin to the standard treatment of Colorectal Cancer could
decrease treatment-associated side effects and enhance
chemotherapy efficacy. Therefore, considering that
therapy-induced toxicity is among the most important factors
limiting cancer treatment and is usually associated with
discontinuation of potentially effective therapy, we suggest
that adding curcumin, a natural compound with a very low
toxicity profile in humans, to current Colorectal Cancer
treatment regimens could be a potential synergistic strategy to
reduce chemotherapy-related adverse effects, improve treatment
efficacy, and decrease drug resistance.
The protective effects of curcumin on depression:
Genes, transcription factors, and microRNAs involved
Journal of Affective Disorders | December 2022 Curcumin is
one of the natural compounds that have been developed for
depression therapy. Curcumin, the main therapeutic component of
turmeric (Curcuma longa), has long been recognized for
its significant anti-inflammatory and antioxidant properties due
to its unique molecular structure (Duc et al., 2021; Nguyen and
Kim, 2021; Nguyen et al., 2021c). Curcumin is well-known for its
potential as a neuroprotective compound against depression.
Curcumin has also been shown to possess physiological effects
that are comparable to those of typical antidepressant
medications (Ramaholimihaso et al., 2020). Curcumin may have an
anti-depressant effect via the relevant genes. We also observed
74 miRNAs associated with depression that are targeted by
curcumin, with hsa-miR-146a-5p having the greatest expression
and interaction. Curcumin's physicochemical
characteristics and pharmacokinetics are consistent with its
antidepressant effects due to its high gastrointestinal
absorption, which did not remove it from the CNS, and its
ability to penetrate the blood-brain barrier. Curcumin also
inhibits CYP1A9 and CYP3A4. Our data mining found that
curcumin's antidepressant effects were regulated by 14 different
genes. The GeneMANIA prediction plug-in presented interaction
types among the identified genes targeted by curcumin's possible
benefits to counteract the development of depression. Converging
evidence indicates that curcumin has been shown to exert
modulating effects on neuroplasticity, insulin resistance,
inflammatory pathways, excitotoxicity, neurotransmitter levels,
nitrosative and oxidative stress, hypothalamic-pituitary-adrenal
disturbances, and the endocannabinoid system, all of which can
be implicated in the pathophysiology of depression (Ramaholimihaso
et al., 2020).Our findings suggest that curcumin may have a
possible anti-depressant impact via the following genes:
ADORA2A, ALB, BDNF, FGF2, GLO1, GSK3B, IL6, MIF, NOS1, PTGS2,
RELN, SELP, SOD1, and NR3C1.
Mechanism of apoptosis activation by Curcumin
rescued mutant p53Y220C in human pancreatic cancer
Molecular Cell Research | December 2022 Based on our studies,
it reflects that apoptosis in pancreatic cancer cells is
mediated by curcumin-rescued mutant p53Y220C. In this study, we
have shown through different biophysical and cell-based studies
that curcumin binds and rescues mutp53Y220C to an active
wild-type conformation and restores its apoptotic transcription
function in BxPC-3-pancreatic cancer cells. In addition, the
curcumin-rescued-p53Y220C (CRp53) showed significant
hyperphosphorylation at Ser15, Ser20, and acetylation at Lys382
with an 8-fold increase in transcription activity in the BxPC-3
cell lines.
An in silico investigation on the interactions of curcumin
and epigallocatechin-3-gallate with NLRP3 Inflammasome complex
Biomedicine & Pharmacotherapy | December
2022 The binding energies of curcumin and inhibitor MCC950
are almost identical. Curcumin and EGCG, plant-derived
compounds, inhibit the NLRP3-mediated IL-1β and IL-18
production. Curcumin and epigallocatechin-3-gallate (EGCG)
suppress the activation of the NLRP3 inflammasome. Our data
showed that NLRP3 had a higher binding affinity for curcumin and
EGCG than other complex proteins. The therapeutic effect of
curcumin and EGCG may be due to the inhibition of inflammasome
activation. The molecular and protein-protein interaction data
indicated that the therapeutic effects of these two polyphenols
are mediated by preventing the development of the NLRP3 complex.
MACC1-Dependent Antitumor Effect of Curcumin in Colorectal
Cancer Nutrients | November 2022
Curcumin is the curcuminoid compound of turmeric (Curcuma
longa). Its remedial effect was shown for various diseases, such
as Alzheimer’s and gastrointestinal disorders. Recent studies
also demonstrated curcumin’s inhibitory impact on cancer
progression and distant dissemination of tumors. Curcumin is
able to inhibit proliferation and induces apoptosis. Further
studies revealed that curcumin treatment enhances G1/S cell
cycle arrest. Moreover, curcumin treatment induces autophagy
through the suppression of the AKT/mTOR/p70S6K pathway. In
addition to these, its effect on angiogenesis, cancer stemness,
and NFκB signaling was reported in different tumor entities.
Preliminary studies indicated the potential inhibitory effect of
curcumin on prostate cancer metastasis by decreasing the
expression of CXCL1 and 2. Curcumin reduced the
metastasis-associated in colon cancer 1 expression, restricted
the metastasis-associated in colon cancer 1-induced
proliferation, and was able to reduce the metastasis-associated
in colon cancer 1-induced cell motility as one of the crucial
steps for the distant dissemination of the tumor. We further
showed the metastasis-associated in colon cancer 1-dependent
effect of curcumin on clonogenicity and wound healing. This
study is, to our knowledge, the first identification of the
effect of curcumin on the restriction of cancer motility,
proliferation, and colony-forming ability by using
metastasis-associated in colon cancer 1 as a target. Taken
together, we illustrated the prominent inhibitory effect of
curcumin on MACC1 expression and MACC1-induced phenotypes. In
addition, we further revealed the MACC1-dependent
anti-proliferative and anti-migratory effects of curcumin.
Although the experiments have been conducted in the established
cell lines, these promising results can expand in the other
models so that curcumin can further supplement the treatment of
CRC patients, notably those who cannot tolerate statins and have
high MACC1 expression. This is the first study showing the
effect of curcumin on reducing MACC1 expression in the
established cell lines. In this study, we demonstrated the
MACC1-dependent inhibitory effect of a wide range of curcumin
concentrations on MACC1-induced viability, proliferation,
migration, wound healing, and clonogenicity.
Effects of curcumin, a bioactive component of turmeric, on type
2 diabetes mellitus and its complications: an updated review
Food & Function | November 2022 Among
the herbal supplements, turmeric (Curcuma longa L.) has
been attracting an avalanche of attention owing to its main
component, curcumin. This review examines the physiological
activities and mechanisms of action of curcumin associated with
type 2 diabetes and its complications. The anti-diabetic
characteristic of curcumin is mainly attributed to its
anti-inflammatory as well as anti-oxidant activities. In
addition to these activities, curcumin has been developed as a
promising prevention/treatment choice for diabetes complications
by modulating various critical signal steps owing to the
anti-hyperglycemic and anti-hyperlipidemic activities of
curcumin. Studies on diabetic humans and animals have revealed
that curcumin may have positive effects on oxidative stress and
inflammation and may reduce fasting blood glucose levels,
increase insulin sensitivity/secretion and regulate the lipid
profile. Thus, it may prevent and treat diabetes by affecting
various molecular targets.
Curcumin Represses Colorectal Cancer Cell Proliferation by
Triggering Ferroptosis via PI3K/Akt/mTOR Signaling
Nutrition and Cancer | November 2022
Curcumin is known to suppress the progression of
colorectal cancer by inhibiting cancer cell proliferation. In
this study, we explored the role of ferroptosis in the
antiproliferative properties of curcumin. The effect of curcumin
on ferroptosis In Vitro was evaluated in HCT-8 cells.
Ferroptosis was first blocked by ferrostatin-1 and the
antiproliferative effect of curcumin was evaluated by
determining the levels of ferroptotic markers, including
glutathione, SLC7A11, GPX4, iron, malondialdehyde, and reactive
oxygen species. Curcumin repressed HCT-8 cell proliferation in a
dose-dependent manner. Treating HCT-8 cells with curcumin
significantly downregulated GSH, SLC7A11, and GPX4, while
significantly increasing levels of iron, MDA, and ROS. In
addition, curcumin promoted ferroptosis and reduced
proliferation of HCT-8 cells by suppressing the PI3K/Akt/mTOR
pathway, and these effects were antagonized by Fer-1. The
effects of curcumin were antagonized by a PI3K agonist and
reinforced by a PI3K inhibitor. Curcumin triggers ferroptosis
and suppresses proliferation of colorectal cancer cells by
inhibiting the PI3K/Akt/mTOR signaling pathway. These results
indicate its potential as a treatment against colorectal cancer.
Neuroprotective Activities of Curcumin in
Parkinson’s Disease: A Review of the Literature
International Journal of Molecular Sciences | November 2022
Curcumin is a neuroprotective agent with antioxidant,
anti-inflammatory, free radical scavenging, mitochondrial
protecting, and iron-chelating properties, which enhance DA
levels in the brain. Curcumin is a polyphenolic compound
isolated from the rhizomes of Curcuma longa (turmeric). It has
been demonstrated to have potent anti-inflammatory, antioxidant,
free radical scavenging, mitochondrial protecting, and
iron-chelating effects, and is considered a promising
therapeutic and nutraceutical agent for the treatment of
Parkinson’s disease. The interaction of curcumin with α7-nACh
receptors provides further evidence for a potential
neuroprotective role for curcumin in Parkinson’s disease.
Additionally, curcumin and derivatives show a high safety
profile with minimal reported toxicity as demonstrated both in
in vitro and in in vivo studies in Parkinson’s disease models.
Therefore, gaining a better understanding of the neuroprotective
properties of curcumin could have significant therapeutic
implications. The evidence reviewed supports curcumin’s powerful
molecular and cellular effects in neurodegenerative disorders as
an appealing strategy for improving Parkinson’s disease
management and prognosis. Perkins and colleagues reported that
humans require a daily dose of 1.6 g curcumin to achieve the
desired results. Concomitant administration of piperine with
curcumin significantly reduced elimination and half-life
clearance of curcumin.
Schizophrenia,
Curcumin and Minimizing Side Effects of Antipsychotic Drugs:
Possible Mechanisms Neurochemical Research
| November 2022 Curcumin has important therapeutic properties
such as antioxidant, anti-mutagenic, anti-inflammatory, and
antimicrobial functions and protection of the nervous system.
Also, the ability of curcumin to pass the blood-brain barrier
raises new hopes for neuroprotection. Curcumin can improve and
prevent further probable neurological and behavioral disorders
in patients with schizophrenia. Alternative therapy such as
curcumin can reduce the severity of symptoms without significant
side effects. It decreases the side effects of neuroleptics and
retains lipid homeostasis. Curcumin increases the level of
brain-derived neurotrophic factor and improves hyperkinetic
movement disorders. Curcumin may act as an added counteraction
mechanism to retain cell integrity and defense against free
radical injury. Thus it appears to have therapeutic potential
for improvement of schizophrenia. In this study, we review
several properties of curcumin and its ability to improve
schizophrenia and minimize the side effects of antipsychotic
drugs, and we explore the underlying mechanisms by which
curcumin affects schizophrenia and its symptoms.
Glutathione
Compared to Curcumin in the Management of Systemic Lupus
Erythematosus: A Systematic Review Cureus |
November 2022 Curcumin can be a more promising alternative
since it operates on various pathways and is a more easily
accessible source. Based on the data available, curcumin shows a
broader range of applications. It has actions on many more
pathways. Hence, curcumin is a more apt drug for usage soon.
Curcumin is a more available, naturally occurring compound. In
addition, some studies also indicate the effect of curcumin on
glutathione function. Curcumin also has more studies proving its
role in the management of SLE, thus making it a safer bet for
case management. The ability of curcumin to interact with
several immunomodulatory pathways makes it so valuable for
managing autoimmune diseases. The activation of oxidative
pathways is how curcumin's anti-inflammatory role is activated.
Curcumin targets the inhibitor of kappa-B kinase subunit beta
(IKKβ) of the NFκB pathway to help reduce inflammation. NFκB
downregulation by curcumin minimizes the release of nitric
oxide, ILs, and various other inflammatory markers from the T
cells. Curcumin also prevents neutrophil chemotaxis, thus
reducing inflammatory responses in tissues. Curcumin acts by
causing impairment in the formation of pro-inflammatory markers.
Curcumin plays a role in adjusting the levels of inflammatory
markers from cells. It reduced IL types 4, 6, and 8 and tumor
necrosis factor (TNF) alpha. Reducing free radicals in the body
helps reduce inflammatory changes in tissues.
Curcumin improves insulin sensitivity in high-fat
diet-fed mice through gut microbiota Nutrition
& Metabolism | November 2022 Curcumin is a polyphenolic
compound extracted from tropical plant Curcuma longa, and as a
phytochemical derived from a medicinal and edible food, it not
only has an extremely low level of toxicity but also has been
used in traditional medicine to improve metabolic diseases.
Moreover, curcumin has been shown to improve metabolic syndrome
in basic research, and its potential efficacy in improving
diabetes has also been demonstrated in clinical trials.
Therefore, curcumin has excellent prospects for clinical
application in the prevention and treatment of insulin
resistance. In a recent study by our research team, gut
microbiota were shown to mediate the enhancement of uncoupling
protein 1-dependent thermogenesis by curcumin in high-fat
diet-fed mice, while curcumin increased energy consumption by
improving high-fat diet-induced gut microbiota dysbiosis and
hence ameliorating high-fat diet-induced obesity in mice.
Accordingly, we speculated that curcumin may exert its
protective effects against insulin resistance via gut microbiota
modulation. We believe this knowledge would provide a
theoretical basis for the clinical application of curcumin in
the prevention and treatment of metabolic syndrome and type 2
diabetes, as well as new ideas for the treatment of metabolic
diseases. Curcumin-restructured fecal microbiota produced
similar effects to curcumin, while also confirming that curcumin
improved insulin sensitivity through gut microbiota modulation
in high-fat diet-fed mice. This study demonstrated that curcumin
ameliorated high-fat diet-induced GLMDs and increased insulin
sensitivity, and verified that the beneficial effects of
curcumin required its modulation on gut microbiota. Moreover, we
found that curcumin upregulated the expression of the
gut-derived hormone FGF15, and this upregulation was also
dependent on gut microbiota. Our findings suggested that
curcumin at least partly exert its effects on increasing insulin
sensitivity via FGF15 upregulation in high-fat diet-fed mice.
This study provided a theoretical basis for the clinical
application of curcumin in the treatment of metabolic syndrome
and type 2 diabetes. In addition, it is hoped that our findings
will provide novel ideas on nutritional manipulations of gut
microbiota for the treatment of metabolic diseases.
Curcumin and Its Analogs in Non-Small Cell Lung Cancer
Treatment: Challenges and Expectations
Biomolecules | November 2022 Curcumin, a natural polyphenolic
compound extracted from the root of turmeric, possesses diverse
pharmacologic activities, including anti-diabetes, anti-aging,
anti-Parkinson’s disease and Alzheimer’s disease,
anti-cardiovascular disease, and anti-cancer, etc. Specifically,
in tumor treatment, modern medicine has demonstrated that
curcumin exerts therapeutic effects on various cancers,
including breast cancer, colorectal neoplasm, liver carcinoma,
glioblastoma, gastric tumor, and lung carcinoma, etc. We
determined via a PubMed database search that researchers first
reported assessing curcumin as an anticancer drug in 1985. Ten
years later, investigators found that Cur could suppress lung
tumor metastasis and extend the life span of mice. Since then,
many non-small cell lung cancer (NSCLC) preclinical studies
revealed that curcumin could inhibit tumor nodules ; restrain
cancer stem cells; control the cell cycle; suppress immigration,
invasion, and repair; induce the production of ROS and ER
stress; trigger apoptosis; elevate DNA damage and ferroptosis;
and promote necrotic cell death, thereby treating and preventing
NSCLC. The broad actions through which curcumin can affect
non-small cell lung cancer (NSCLC) in vitro and in vivo are
summarized. Considerable preclinical evidence has revealed that
curcumin and its analogs affect non-small cell lung cancer
(NSCLC) via various mechanisms, such as inducing ROS production,
increasing ferroptosis, changing mitochondrial potential, and
disturbing cellular signaling pathways. Additionally,
co-treatment with curcumin and other agents synergistically
enhances cytotoxicity in non-small cell lung cancer (NSCLC)
cells to suppress tumor cell growth, migration, and invasion.
This evidence suggests that curcumin and its analogs offer
promise to prevent non-small cell lung cancer (NSCLC) in humans.
Quinacrine and Curcumin in combination decreased the
breast cancer angiogenesis by modulating ABCG2 via VEGF A
Journal of Cell Communication and Signaling | November 2022
Curcumin + QC inhibited the proliferation, invasion, migration
and expression of representative markers of metastasis and
angiogenesis. Curcumin + QC inhibited the ABCG2 expression and
thus reduced the angiogenesis. Reduction of vascularization was
also observed after treatment of Curcumin + QC.
Curcumin + QC inhibited the process by inhibiting ABCG2 in
breast cancer.
Combination of curcumin and piperine synergistically
improves pain-like behaviors in mouse models of pain with no
potential CNS side effects CM Journal |
November 2022 For centuries, turmeric containing curcumin and
Piper nigrum containing piperine have been used as food
additives and folk medicine, including Traditional Chinese
Medicine. The combination of C. longa curcumin, and
P. nigrum piperine, has been used in traditional medicine.
Many recent studies reported synergistic effects of curcumin and
piperine combination in various pharmacological models,
including lung cancer, aging, and hepatocellular carcinoma.
Curcumin has also been reported as a potential analgesic both in
animals and humans and exhibits diverse cellular and molecular
targets. Curcumin inhibits pain neurotransmission by modulating
immune and neuronal cells at cellular and mechanistic levels. In
animal models of pain, curcumin suppresses pro-inflammatory
mediators and increases endogenous anti-inflammatory mediators
by modulating peripheral and central immune cells. The present
study demonstrates strong antinociceptive synergism between
curcumin and piperine in mouse models with no potential CNS side
effects, suggesting its possible use in clinical trials.
The combination of curcumin and piperine produced synergistic
interaction in the formalin, tail-flick, and cold plate tests.
The synergistic interaction of curcumin and piperine was further
confirmed by the efficacy of the combination in LPS-stimulated
RAW 264.7 macrophage cells. Curcumin and piperine interacted
synergistically, reducing proinflammatory mediators. The
combination also demonstrated better compatibility profiles with
neuronal cells. The combination of curcumin and piperine
synergistically ameliorates pain-like behaviors in the mouse
formalin model. Curcumin and piperine significantly ameliorate
formalin-induced peripheral and central inflammation. Curcumin
and piperine synergistically attenuate inflammatory response
in-vitro. The curcumin-piperine combination at the highest
dose exhibited significantly lesser expression of
pro-inflammatory cytokines compared to the individual treatment
at respective concentrations. Curcumin-piperine combination
showed better compatibility with neuronal cells compared to
individual treatments. The combination of curcumin and piperine
synergistically interacts in suppressing pain-like behaviors
induced by heat stimuli. The combination of curcumin and
piperine synergistically interacts in suppressing pain-like
behaviors by cold stimuli. Reduction in locomotive behaviors was
not observed with the curcumin-piperine combination, indicating
no potential CNS side effects of curcumin-piperine combination
at its highest therapeutic doses. Curcumin and piperine
interacted synergistically, suppressing inflammatory mediators
with favorable compatibility with neuronal cells. Curcumin and
piperine have been shown to interact synergistically in various
preclinical pharmacological studies. The combination of curcumin
and piperine elicited a greater antinociceptive effect compared
to that of either curcumin or piperine alone. The isobolographic
analysis was performed to evaluate the type of interaction,
wherein strong antinociceptive synergism between curcumin and
piperine was found. This interaction produced by the combination
of these two compounds could be due to their pharmacodynamic and
pharmacokinetic interactions. Pharmacodynamically, the
combination of curcumin and piperine could simultaneously
inhibit multiple sites of action in the pain pathway. The
ability of curcumin and piperine to modulate diverse pathways of
pain could lead to robust inhibition of pain transmission when
those are coadministered. Hence, the pharmacodynamic interaction
between curcumin and piperine could be one of the potential
reasons for the observed antinociceptive synergism in this
study. In addition, it has also been proved that piperine can
increase the delivery of curcumin to systemic circulation due to
its ability to improve the pharmacokinetic profiles of curcumin.
Piperine was reported to increase the bioavailability of oral
curcumin: 154% and 2000% increase in curcumin concentration in
the plasma was observed in rats and humans, respectively. The
increased concentration of curcumin in the bloodstream is due to
the ability of piperine to decrease the rate of metabolism of
curcumin in the intestine and liver. In the intestine, piperine
regulates membrane lipid dynamics and inhibits the intestinal
metabolism of curcumin, leading to enhanced curcumin retention
in the intestine. Furthermore, piperine reduces the rate of
curcumin metabolism in the liver by hindering aryl hydrocarbon
hydroxylation, ethylmorphine-N-demethylation,
7-ethoxycoumarin-O-deethylation, and 3-hydroxy-benzo(a)pyrene
glucuronidation and glucuronidation, which subsequently reduce
the first-pass metabolism of curcumin. Hence, coadministration
of piperine and curcumin enhances the oral bioavailability of
curcumin, and thereby, its therapeutic efficacy. This factor may
also have influenced the strong antinociceptive synergism
observed in this study. Cells treated with the curcumin-piperine
combination at their EC90 concentration showed no toxicity to
neuronal cells. We found no effects of the individual curcumin
and combination on the spontaneous locomotor activity at their
high doses, while individual piperine reduced locomotor
activity. The results indicate no potential CNS side effects of
the curcumin and piperine combination.
Curcumin Sensitizes 4T1 Murine Breast Cancer Cells
to Cisplatin In Vivo | November 2022
Curcumin, which is highly effective at inducing cell death in
various types of cancer, is a polyphenolic yellow pigment
derived from Curcuma longa. It can selectively chemosensitize
tumor cells, thereby protecting normal cells from chemotherapy
and radiotherapy. In this study, treatment of mice with curcumin
led to a decrease in tumor mass. Treatment with curcumin
followed by cisplatin led to complete tumor mass regression in
mice compared with the control group. Zhao et al. reported that
high levels of PAR4 in the serum and plasma of mice inhibited
the growth of metastatic lung tumor nodules derived from Lewis
lung carcinoma cells in syngeneic mice. Curcumin is a good
inducer of PAR4 expression in breast cancer cells and a
secretagogue in non-tumor cells in vivo. In addition, it
sensitizes cells to the effect of cisplatin; hence, curcumin,
alone or in combination with chemotherapy, might be used as an
alternative treatment for breast cancer.
Curcumin Prevents Diabetic Osteoporosis through
Promoting Osteogenesis and Angiogenesis Coupling via NF-κB
Signaling Evidence-Based Complementary and
Alternative Medicine | November 2022 Curcumin, an effective
component extracted from Curcuma longa, exhibits antioxidation,
regulation of bone metabolism and hypoglycemic effects.
Treatment prevented bone loss and promoted vessel formation in
diabetic osteoporosis mice. Based on these results, we concluded
that curcumin ameliorated diabetic osteoporosis.. Reports
demonstrate that curcumin may ameliorate bone microarchitecture
and enhance BMD in APP/PS1 transgenic mice and has shown bone
protective effect on postmenopausal osteoporosis animal models
and patients. More importantly, recent studies have found the
therapeutic value of curcumin on osteoporosis induced by
diabetes. The benefits of curcumin on bone formation and
regeneration are attributed to its capacity to reduce
H2O2-stimulated osteoblast apoptosis, improving osteoblast
mitochondrial function, and recovering the high glucose-impaired
osteogenic differentiation of osteoblast and BMSCs. To our
knowledge, this is the first to confirm that curcumin prevents
diabetes-induced bone loss by promoting BMSC-mediated
osteogenesis and angiogenesis coupling. In this study, our
results showed that curcumin treatment rescued high
glucose-inhibited osteogenic differentiation ability of BMSCs in
vitro. Furthermore, our in vivo results also revealed that
curcumin prevented bone loss in diabetic mice. Our findings
reveal the effects of curcumin in promoting the BMSCs-mediated
osteogenesis and angiogenesis coupling in high glucose
conditions. These impacts are preliminarily considered to be via
NF-κB signaling pathway inhibition. Furthermore, curcumin may
become a potential drug to prevent and treat diabetic
osteoporosis through promoting bone regeneration and vessel
formation.
In patients with osteoarthritis, is curcumin,
compared to placebo, effective in reducing pain?
Journal of the Oklahoma State Medical Association | November
2022 Yes. Studies have shown that curcumin extract has
benefit in treating osteoarthritic pain, compared to placebo. It
is reasonable to use curcumin in addition to traditional
osteoarthritis treatments, as studies show it has a low side
effect profile. Curcumin is a bright yellow powder derived from
turmeric, and has been used for centuries in alternative
medicine for its anti-inflammatory properties. Subjects took 500
mg of curcimin plus 5 mg piperine extract (to enhance
bioavailability) three times daily for 6 weeks. WOMAC
scores for patients taking curcumin averaged 37, while those
taking placebo averaged 57. Results from this literature review
suggest that curcumin can be considered by physicians as an
adjunctive therapy to traditional therapies for osteoarthritis,
as it does appear to offer benefit in pain relief compared to
placebo. Although more evidence is needed to support curcumin as
a replacement for NSAIDs or other mainstay therapies, the
results of the studies reviewed are promising. Larger trials to
investigate the efficacy of curcumin compared to NSAIDs would be
appropriate. However, curcumin appears to be a safe and
effective addition to osteoarthritis treatments for patients,
and should not be overlooked by physicians.
Curcumin protects retinal neuronal cells against
oxidative stress-induced damage by regulating mitochondrial
dynamics Experimental Eye Research |
November 2022 Data indicate that curcumin protects against
oxidative stress-induced injury in retinal neuronal cells by
promoting mitochondrial fusion. Curcumin has anti-inflammatory,
antimutagenic and antimicrobial properties, and has been
administrated for asthma, diabetes and cancer in traditional
medicine for a long history (Nabavi et al., 2015; Qadir et al.,
2016; Shahid et al., 2019). Curcumin has been found to regulate
the apoptosis, proliferation, transformation and metastasis of
cancer cells by inhibiting NF-κB signaling (Aggarwal et al.,
2006). Curcumin also exerts its anti-inflammatory function via
downregulation of COX-2, PGE-2 and proinflammatory factors
including IL-1, 6, 8 and TNF-α or upregulation of peroxisome
proliferator-activated receptor-γ (Michalik et al., 2006; Taylor
and Leonard, 2011). In addition, several studies indicate that
curcumin also shows therapeutic effect on several retinal
diseases including primary retinitis, age-related macular
degeneration, diabetic retinopathy and glaucoma (Nebbioso et
al., 2021). Pretreatment with curcumin effectively attenuated
H2O2-induced mitochondrial fission, and inhibited the
intracellular ROS generation, mitochondrial membrane potential
disruption, PINK1 expression, caspase-3 cleavage and apoptosis
in R28 cells. Notably, knockdown of mitochondrial fusion protein
Mfn2 dramatically attenuated curcumin's protection against
H2O2-induced growth inhibition in R28 cells. In conclusion, our
results indicate that mitochondrial fusion plays a vital role in
curcumin-mediated protection against oxidative stress-induced
retinal neuronal damage, and also suggesting mitochondria as a
crucial target for the protection of neurons.
Effects of curcumin-piperine supplementation on
systemic immunity in young women with premenstrual syndrome and
dysmenorrhea: A randomized clinical trial
European Journal of Obstetrics, Gynecology, Reproductive Biology
| November 2022 Curcumin decreased the serum immunoglobulin E
(IgE) levels in women with premenstrual syndrome and
dysmenorrhea. Curcumin + piperine treatment was associated with
a significant reduction in the mean serum levels of
immunoglobulin E (IgE). Curcumin plus piperine might have
positive effect on serum immunoglobulin E (IgE) levels with no
significant changes on serum IL-10 and IL-12 in healthy young
women with PMS and PD. Studies with higher doses and longer
durations of treatment with curcumin are required to confirm
these findings.
Alzheimer’s disease large-scale gene expression
portrait identifies exercise and curcumin as top theoretical
treatments Scientific Reports | October
2022 For the Alzheimer’s disease portrait, the top three
scoring treatments for reversing Alzheimer’s disease expression
with little effect on exacerbating Alzheimer’s disease
expression were for exercise. Overall, the ranking of treatments
was similar for male and female portrait, although in males,
curcumin was the second highest ranked treatment.
Isolation and In silico Study of Curcumin from
Curcuma longa and Its Anti-Diabetic Activity
Applied Biochemistry and Biotechnology | October2022 The
development of new drugs from natural products is still
challenging, and the most extensively studied plant material is
turmeric, Curcuma longa, which is the chief source of
curcumin. Curcumin is a bright yellow solid. Based on the
findings, it can be said that curcumin, a natural substance, has
good therapeutic qualities when it is isolated.
The Pharmacological Mechanism of Curcumin against
Drug Resistance in Non-Small Cell Lung Cancer
Evidence-Based Complementary and Alternative Medicine | October
2022 Curcumin is commonly utilized for the treatment of
various cancers (e.g., breast cancer and hematological cancers).
It has been found to have anticancer activity in non-small
cell lung cancer. Increasing evidence showed that curcumin could
enhance immune function via various mechanisms. It was revealed
that curcumin could enhance tumor antigen-specific T-cell
induction in cancer cells. Curcumin inhibited CSN5 expression in
cancer cells and sensitized them to anti-CTLA4 therapy.
Additionally, curcumin could reverse resistance to targeted
medicines. Curcumin overcomes primary gefitinib resistance in
non-small cell lung cancercells by causing cell death related to
autophagy. Curcumin enhances gefitinib’s sensitivity by
inhibiting cell proliferation and suppressing clonogenic
capacity in NCI-H1975 cells. Curcumin can also enhance the
effect of chemotherapy drugs. A previous study demonstrated that
curcumin and doxorubicin work together more effectively in
treating Hodgkin lymphoma. Curcumin in combination with
immunotherapy, chemotherapy, or targeted drugs has the potential
to be effective for drug-resistant non-small cell lung cancer.
Curcumin regulates drug sensitivity in non-small cell lung
cancerby interacting with cell cycle, NF-kappa B, MAPK, Th17
cell differentiation signaling pathways, etc. The findings of
our study reveal the relevant key signaling pathways and targets
of curcumin as an adjuvant therapy in the treatment of non-small
cell lung cancer, thus providing pharmacological evidence for
further experimental research.
Antitoxic Effects of Curcumin against
Obesity-Induced Multi-Organs’ Biochemical and Histopathological
Abnormalities in an Animal Model
Evidence-Based Complementary and Alternative Medicine | October
2022 Curcumin exerted potent antitoxic, antioxidant,
tissue-protective, and antiobesity effects. Curcumin is
recommended to be added to various dietary regimens to prevent
or delay the organs’ dysfunction among obese people. The most
significant phenolic ingredient in turmeric is called curcumin,
and it is yellow in color and is a natural phenolic antioxidant.
Due to its biological and pharmacological characteristics, which
include antioxidant and anti-inflammatory features, curcumin has
received a lot of interest in various research studies,
including human or experimental animal models in various
diseases, including obesity. Genetic analyses of the related
inflammatory signaling pathways (via assessments of adipose
tissue expressions of TLR4, IL-6, and TNF-α) were performed to
explore the potential mechanistic benefits of curcumin in
reversing these metabolic abnormalities. Coadministration of
curcumin with a high-fat diet group exhibited significantly
decreased serum insulin and glucose levels when compared with
the high-fat diet group. In parallel with our results, Hartogh
et al. reported that by lowering the harmful effects of liver
fat and increasing cell sensitivity to insulin, curcumin can
lower blood glucose levels in obese rats. The present results
could be attributed to the ability of curcumin to reduce
oxidative stress and inflammatory response which contributed to
insulin resistance. Similarly, curcumin treatment attenuated
glucose intolerance and boost insulin sensitizing response.
Furthermore, curcumin administration caused strong induction of
the antioxidant defenses, since SOD, CAT, and GSH-Px activities
were significantly increased, reaching values similar to those
of the control group. Curcumin’s effects may act by either
directly scavenging the reactive oxygen metabolites or due to
the presence of various antioxidant principles such as
flavonoids, steroids, tannins, glycosides, triterpenoids, and
polyphenolic compounds. The anti-inflammatory effects of
curcumin form the basis of its potential clinical applications.
In the present study, curcumin significantly reduces the
inflammation state in high-fat diet group. Curcumin is an
excellent antioxidant agent and has an effective role in the
regression of DNA damage. Interestingly, the current study
demonstrated that administration of curcumin to the high-fat
diet group provided protection against hepatic disorders,
duodenal and myocardial histopathological changes as confirmed
by these results are in line with those of many researchers who
found a marked reduction in steatosis of hepatocytes and an
improvement in liver histopathology. It is likely to postulate
that the antioxidative property of curcumin is the key to its
therapeutic effect on gastrointestinal injury as documented by
many researchers. Moreover, Gorabi et al. revealed that high-fat
diet plus curcumin showed no histopathological changes in the
myocardial structure, indicating a preventive effect of curcumin
against histological cardiac changes induced by a high-fat diet.
There is no doubt that the use of curcumin improved the
histological findings as well as modulated metabolic and
oxidative stress markers, as well as downregulated inflammatory
biomarkers and apoptosis. Therefore, it is advised that curcumin
be evaluated as a possible supplemental therapy for metabolic
diseases linked to obesity brought on by high-fat diet.
Curcumin
strengthens immunity by helping the generation of immune cells
such as T cells and B cells International
Curry and Spices Symposium | October 2022 Immune cells such
as B cells increased significantly in the lymph glands of rats
administered with curcumin. Curcumin helps to produce antibodies
and can contribute to the prevention of various infectious
diseases such as the flu and colds and cancer. Curcumin is a
yellow pigment component of turmeric, the main ingredient in
curry, and is known to have excellent antioxidant and
anti-inflammatory effects. Curcumin in turmeric has anti-cancer,
anti-inflammatory, and antioxidant effects by inhibiting the
activity of inflammation-related genes.
Roles of Curcumin on Cognitive Impairment Induced by
a Mixture of Heavy Metals Neurotoxicity
Research | October 2022 The most important pathways involved
in curcumin's protective activity against heavy metals were
categorized as "regulation of neuron apoptotic process” and
"negative regulation of apoptotic signaling route”. Curcumin was
also well-positioned inside the CASP3 binding region. Three key
miRNAs linked to cognitive impairment, mixed heavy metals, and
curcumin were observed. These miRNAs were found to be related to
the important pathways related to cognitive impairment and
involved in curcumin's protective activity against mixed heavy
metals such as "apoptosis multiple species”, “apoptosis”, and
“Alzheimer’s disease”. Curcumin's physicochemical
characteristics and pharmacokinetics are consistent with its
therapeutic benefits in cognitive impairment, owing to its high
gastrointestinal absorption and ability to cross the blood–brain
barrier. Our findings emphasize the protective effects of
curcumin in cognitive impairment caused by heavy metal mixtures
and pave the way for molecular mechanisms involved in cognitive
impairment pathology.
Protective effects of curcumin against traumatic
brain injury Biomedicine & Pharmacotherapy
| October 2022 Curcumin has a broad range of clinical
properties due to its considerable antioxidative and
anti-inflammatory actions. This review discusses the pleiotropic
mechanisms, the side effects, curcumin's delivery to the central
nervous system (CNS), and its immunomodulatory and protective
effects on traumatic brain injury. Clinical trials, in
vivo, and in vitro studies were extracted from different
scientific databases, including PubMed, Scopus, and Google
Scholar, to assess the effects of curcumin or its derivatives in
traumatic brain injury. Findings reveal that curcumin exhibited
some protective effects on traumatic brain injury via
modulation of cell signaling pathways including toll-like
receptor-4 (TLR-4), nuclear factor kappa B (NF-κB), and Nod-like
receptor family proteins (NLRPs). Moreover, curcumin upregulates
the brain-derived Neurotrophic Factor/Tropomyosin receptor
kinase B (BDNF/TrkB) signaling pathway,
phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT),
nuclear factor erythroid 2-related factor 2 (Nrf2), which have
crucial functions in modulation of TBI
pathophysiological-mediated pathways. Curcumin displays
beneficial immunomodulatory functions and protective capacities
in different traumatic brain injury models.
Curcumin: An overview Journal
of Medicinal Plants Studies | October 2022 Curcumin is the
active ingredient in the herbal remedy and dietary spice
turmeric, having a wide range of therapeutic properties that
covers antimicrobial, immune-health, multiple myeloma and
cancers of various categories. Curcumin has been shown to
exhibit antioxidant, anti-inflammatory, antiviral,
antibacterial, antifungal, and anticancer activities and thus
has a potential against various malignant diseases, diabetes,
allergies, arthritis, Alzheimer's disease, and other chronic
illnesses. Curcumin inhibits the growth of Helicobacter
pylori, which causes gastric ulcers and has been linked
with gastric cancers. Extracts of turmeric and its
curcumin component exhibit strong antioxidant activity
comparable to vitamins C & E. Several studies have demonstrated
curcumin's ability to reduce oxidative stress. It appears that
curcumin's role as an antioxidant may be due in part to its
ability to down regulate nitric oxide formation. It has been
proved already that curcumin down -regulates NF- kappaB in human
multiple myeloma cells, leading to the suppression of
proliferation and induction of apoptosis, thus providing the
molecular basis for the treatment of multiple myeloma with this
pharmacologically safe agent. Pharmacological studies have
demonstrated that curcumin from Curcuma longa is an
anti-mutagen as well as an anti-promotor for cancer.
The Role of Phytochemicals in the Treatment of
Colorectal Cancer Onco Therapeutics |
October 2022 Phytochemicals like curcumin are naturally
occurring and are known to exhibit anti-cancer activity against
colorectal cancer by regulating various key signaling pathways
including the Wnt/β-catenin signaling pathway. By regulating
vital molecular pathways, the course of colorectal cancer can be
positively altered. The evidence outlined within this literature
review suggests the significance of these phytochemicals as
preventive agents and their potential role in developing
effective therapies. This review emphasizes the molecular
mechanisms of curcumin, resveratrol, and sulforaphane that can
effectively target colorectal cancer development and
progression.
Review On Curcuma Longa Effect On Human Health
Journal of Emerging Technologies and Innovative Research |
September 2022 Curcumin is the phytochemical derived from the
bulb of the plant Curcuma longa and is the major
component of turmeric. The herb has been used for thousands of
years. It aids in the management of oxidative and inflammatory
conditions, metabolic syndrome, arthritis, It may also help in
the management of exercise-induced inflammation and muscle
soreness, thus enhancing recovery and performance in active
people. Most of these benefits can be attributed to its
antioxidant and anti-inflammatory effects. Curcumin from the
herb turmeric has been used for thousands of years. It aids in
the management of oxidative and inflammatory conditions,
metabolic syndrome, arthritis, It may also help in the
management of exercise-induced inflammation and muscle soreness,
thus enhancing recovery and performance in active people. Most
of these benefits can be attributed to its antioxidant and anti-
inflammatory effects. It has also demonstrated hepatoprotective,
nephroprotective, neuroprotective, and cardioprotective
properties. These characteristics provide the foundation for its
therapeutic uses and the rationale for clinical trials. Many
other medicinal and pharmacological properties of curcumin used
for humans. In Ayurveda, curcumin has been used for various
medicinal conditions including rhinitis, wound healing, common
cold, skin infections, liver and urinary tract diseases.
Curcumin was found to be effective even when given by different
routes including topical, oral or by inhalation, dependent on
the intended use.
Curcumin Targeting Non-Coding RNAs in Colorectal Cancer:
Therapeutic and Biomarker Implications
Biomolecules | September 2022 Curcumin has shown potent
anti-tumor and anti-inflammatory effects and is considered a hot
spot in the research and development of anti-tumor drugs due to
its advantages of precise efficacy, lower toxic side effects,
and less drug resistance. Recent studies have revealed that
curcumin has anti-tumor effects exerted on the epigenetic
regulation of tumor-promoting/tumor-suppressing gene expression
through the alteration of expression levels of non-coding RNAs.
Curcumin has been approved as a food additive by the World
Health Organization and the US Food and Drug Administration and
has been listed as a third-generation cancer chemoprevention
drug by the National Cancer Institute of the United States due
to its safety, non-toxicity, and lack of adverse effects.
Curcumin has a non-toxic chemical composition; almost all types
of tumor markers can be regulated by it to exert an anti-tumor
effect; undoubtedly, this provides a strong theoretical basis
for cancer treatment. Studies have shown that curcumin could
exert an anti-tumor effect both in vitro and in vivo through
different mechanisms, including inhibiting the invasion,
metastasis, and proliferation of tumor cells, inducing tumor
cell apoptosis and autophagy, and resisting chemotherapy
resistance. Recent studies have shown that curcumin is widely
used as an anti-tumor agent because it regulates ncRNAs based on
an epigenetic regulation mechanism; there are benefits to using
curcumin in the treatment of colorectal cancer. Its
anti-colorectal cancer effect is essentially through the
indirect regulation of target genes or signaling pathways. In
summary, these findings could provide favorable evidence for
exploring the role of curcumin in the treatment of colorectal
cancer via non-coding RNAs, which may provide new directions for
the treatment and prognosis of colorectal cancer patients.
Curcumin could affect the development of colorectal cancer by
targeting oncogenes or tumor-suppressor genes; its
anti-colorectal cancer effect is essentially through the
indirect regulation of target genes or signaling pathways.
Treated by curcumin, Lnc NBR2, Lnc KCNQ1OT1, Lnc PANDAR, and Lnc
CCAT1 could prove to be potentially effective target molecules
in the treatment progress of colorectal cancer. In
summary, these findings could provide favorable evidence for
exploring the role of curcumin in the treatment of colorectal
cancer via non-coding RNAs, which may provide new directions for
the treatment and prognosis of colorectal cancer patients.
Non-coding RNAs can be potential therapeutic targets for the
occurrence and development of colorectal cancer, and
curcumin-targeted non-coding RNAs have good biomarker and
reference significance for the treatment of colorectal cancer.
The effect of eight weeks of Pilates with curcumin
supplementation on liver enzymes and lipid profile in overweight
and obese women Obesity Medicine |
September 2022 Curcumin supplement significantly improve
liver enzymes. Pilates training plus Curcumin supplement
significantly decreased anthropometry indices. Pilates and
Curcumin alone or in combination led to significant changes in
lipid profile. The results showed that weight, BMI, WHR and PBF
decreased in the curcumin + Pilates group compared to the other
groups. According to the results, an 8-week Pilates and curcumin
alone or in combination reduced serum ALT, LDL-C, TG and T-Chol
compared with the control group. Also, serum AST levels
decreased from 23.75 ± 2.14 to 19.37 ± 1.98 in the curcumin
group. Eight weeks of intervention with Pilates and curcumin
alone or in combination seemed effective in improving lipid
profile and reducing ALT enzyme levels in overweight and obese
females. It also appears that the AST enzyme is only affected by
curcumin supplementation.
Curcumin in the treatment of urological cancers:
Therapeutic targets, challenges and prospects
Life Sciences | September 2022 Curcumin has been widely used
in cancer treatment due to its ability to trigger cell death and
suppress metastasis. The beneficial effects of curcumin in the
treatment of urological cancers is the focus of current review.
Curcumin can induce apoptosis in the three types of urological
cancers limiting their proliferative potential. Furthermore,
curcumin can suppress invasion of urological cancers through EMT
inhibition. Notably, curcumin decreases the expression of MMPs,
therefore interfering with urological cancer metastasis. When
used in combination with chemotherapy agents, curcumin displays
synergistic effects in suppressing cancer progression. It can
also be used as a chemosensitizer. Based on pre-clinical
studies, curcumin administration is beneficial in the treatment
of urological cancers and future clinical applications might be
considered upon solving problems related to the poor
bioavailability of the compound.
The effects of curcumin in learning and memory
impairment associated with hypothyroidism in juvenile rats: the
role of nitric oxide, oxidative stress, and brain-derived
neurotrophic factor Behavioural
Pharmacology | September 2022 Curcumin enhanced the
performance of the rats in both MWM and PA tests. In addition,
curcumin reduced malondialdehyde concentration and NO
metabolites; however, it increased thiol content as well as the
activity of catalase and superoxide dismutase enzymes in both
the cortex and hippocampus. Curcumin also increased hippocampal
synthesis of BDNF in hypothyroid rats. The beneficial effects of
curcumin cognitive function in juvenile hypothyroid rats might
be attributed to its protective effect against oxidative stress
and potentiation of BDNF production.
Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis
in Drug-Resistant Cancer Cell Lines Life |
September 2022 The present study shows that curcumin induces
anticancer activity against resistant cancer cell lines in a
concentration and time-dependent manner. The protective
activities of curcumin against the growth of cancer cells are
mediated by modulating oxidative stress, regulating fibrosis,
SIRT1 activation, and inducing cellular apoptosis. The
bio-functional properties of curcumin and its derivatives - such
as anti-tumor, antioxidant, and anti-inflammatory activities -
have gained much attention in combating many human diseases,
particularly cancer. Curcumin’s natural phenolic, hydrophobic,
and antioxidant properties help it to diffuse through cancer
cell membranes into the mitochondria, endoplasmic reticulum, and
nucleus to perform chemo-preventive, antimetastatic, and
anti-angiogenic actions. Curcumin has been reported to exert its
chemotherapeutic efficacy through targeting several molecular
pathways involved in mutagenesis, cell cycle regulation,
tumorigenesis, apoptosis, and metastasis. Moreover, several
studies showed that curcumin significantly reduces fibrosis via
suppressing the overproduction of collagen-linked factors such
as hydroxyproline, fibronectin, and TGF-β1 in cancer cells. In
breast cancer, curcumin is shown to suppress the spread of
cancer cells to other parts of the body. In addition, curcumin
regulates different signaling pathways, especially breast cancer
gene. In colon cancer, curcumin induces FADD (Fas-Associated
Protein With Death Domain), triggering apoptosis. Moreover,
it inhibits colon cancer metastasis. Similarly, in lung cancer,
curcumin modulates the circ-PRKCA/miR-384/ITGB1 pathway,
suppressing the malignancy of lung carcinoma. It also reduces
migration and invasion of lung carcinoma. Curcumin has been
reported to sensitize tumor cells to chemotherapeutic drugs and
ionizing radiation therapy. In conclusion, curcumin induces
anticancer activity against sensitive and drug-resistant cancer
cells in a concentration- and time-dependent manner. The
protective activities of curcumin against the growth of cancer
cells are mediated by modulating oxidative stress, regulating
fibrosis, SIRT1 activation, and inducing cellular apoptosis.
Therefore, curcumin could be tested as an auxiliary therapeutic
agent for current treatments to improve the prognosis in
patients with drug-resistant cancer.
Curcumin as adjuvant treatment in patients with
non-alcoholic fatty liver (NAFLD) disease: A systematic review
and meta-analysis Complementary Therapies
in Medicine | September 2022 Curcumin has been shown to
improve non-alcoholic fatty liver disease’s severity and
increase liver steatosis resolution compared to the placebo
groups. Curcumin was also found to reduce triglycerides if taken
more than eight weeks’ duration. There is no major side
effect, and our findings showed no difference in the adverse
effect. Curcumin is acknowledged as a powerful antioxidant and
anti-inflammatory agent. A review reported that the consumption
of curcumin significantly reduced liver enzymes, decreased
low-density lipoprotein and total cholesterol among
non-alcoholic fatty liver disease patients. Another review found
curcumin showed significant effects on fasting blood sugar,
insulin level, and homeostasis model of assessment insulin
resistance among women with polycystic ovary syndrome. Curcumin
is anticipated to function as antiviral drugs to treat the
current COVID-19 virus based on in vitro and in vivo studies as
it showed high inhibitory activity towards the virus. Goodarzi
and Jalali found that curcumin reduced liver enzymes in
non-alcoholic fatty liver disease compared to the placebo group,
which is similar to our findings. Mansour-Ghanaei and Wei showed
that curcumin reduced aspartate aminotransferase. Our finding is
similar to Jalali that curcumin reduced total cholesterol in
participants compared to the placebo group. Wei and Jalali
showed that curcumin reduced the low-density lipoprotein
compared to the placebo group. Wei also showed that curcumin
reduces triglycerides compared to the placebo group. Curcumin
reduced BMI in participants with the non-alcoholic fatty liver
disease compared to the placebo group. Besides improving the
liver ultrasonographic findings, curcumin also reduced serum
liver enzymes, total cholesterol, and BMI. There is no major
side effect, and our findings showed no difference in the
adverse effect between the two groups. Our meta-analysis shows
that curcumin has favorable effect on liver ultrasonographic
findings, reduced serum liver enzymes, total cholesterol, and
BMI in participants with non-alcoholic fatty liver disease.
Therefore, promoting curcumin as an adjuvant treatment on NAFLD
patients might be justified.
Prevention of Female Reproductive Disorders with the
Help of Curcumin Journal of Antimicrobial
Agents | September 2022 Various examinations on Curcumin have
exhibited its many advantages because of its cell reinforcement,
hostile to disease, against joint inflammation, against
asthmatic, against microbial, against viral and against
parasitic properties. Curcumin shows huge cancer prevention
agent properties by breaking the chain response of free extreme
creation. Likewise, curcumin diminished the protein reactions
engaged with aggravation processes, for example, those of cancer
rot factor alpha, interleukin-1, IL-2, IL-6, IL-8 and IL-12.
Curcumin has been displayed to hinder the actuation of TNF-α in
the NF-κB pathway and kill the receptive oxygen species, causing
oxidative pressure. As oxidative pressure and irritation are in
most persistent sicknesses, curcumin supplementation could
altogether offer different medical advantages. Coorganization of
curcumin with piperine, an alkaloid in dark pepper, improves
curcumin's bioavailability by up to 2000 percent.
Anti-migratory effect of curcumin on A-549 lung
cancer cells Hormone Molecular Biology and
Clinical Investigation | September 2022 Curcumin inhibited
lung cancer cells through various molecular pathways. RECK/MMPs
axis as a regulator of cancer cell migration was modulated after
curcumin treatment and invasion of lung cancer cells was
decreased. The results of MTT assay showed that the cytotoxic
effect of curcumin was in a dose dependent manner. Flow
cytometry results demonstrated a significant increase in the
percentage of apoptotic cells in curcumin treated group. In
addition, curcumin inhibited migration rate in lung cancer
cells.
A network pharmacology approach to identify the
mechanisms and molecular targets of curcumin against Alzheimer's
disease Medicine | September 2022
Curcumin and its metabolites possess anti-inflammatory,
antioxidant, antimicrobial, and antiviral activities. Further,
in recent years, the literature reports that curcumin has
beneficial effects in diseases of the neurological system,
including Alzheimer's disease. Curcumin suppresses the formation
and promotes the disaggregation of amyloid-β plaques, attenuates
the hyperphosphorylation of tau, and enhances its clearance.
available studies indicate that curcumin has been widely used in
neurodegenerative diseases. A recent study indicated that
curcumin could improve lipid metabolic disorders by the ATP
binding cassette A1 transmembrane transport system in
Alzheimer's disease. In addition, curcumin improves parkinsonian
disability scores in vivo and inhibits PC12 cell death in vitro
by inhibiting AKT/mTOR signaling pathway, which is mediated by
autophagy. As valuable targets for Alzheimer's disease
treatment, curcumin can systematically improve the pathological
features of stroke through multifactorial, multitarget, and
multipathway. In summary, curcumin has the potential to be more
effective than current treatments.
Curcumin as a novel approach in improving lipid
profile: An umbrella meta-analysis
Nutrition, Metabolism and Cardiovascular Diseases
| September 2022 Curcumin supplementation significantly
reduced serum levels of LDL-cholesterol, triglycerides and total
cholesterol. Curcumin intake significantly increased
high-density lipoprotein cholesterol (HDL-cholesterol) levels.
Curcumin has ameliorating effects on triglycerides, total
cholesterol, LDL-c, and HDL-c levels. Overall, curcumin could be
recommended as an adjuvant anti-hyperlipidemic agent. We showed
that curcumin supplementation could be effective for lipid
profile.
Antitumor effect of infrared whole-body hyperthermia
with curcumin in breast cancer Medical
Applications | September 2022 Curcumin has traditionally been
used as a food additive or as a remedy in traditional medicine
for its anticancer and non-toxic effects. Thus, this research
proposed the combination of curcumin and IHT as an alternative
to chemotherapy in breast cancer treatment. Results showed that
tumor growth inhibition and body weight gain in the combination
treatment group are significantly different compared
to control. The group also had the longest median survival time
(42 days) with no mortality observed during the experiment. This
result indicates that the combination treatment is well
tolerated by the mice and has negligible levels of toxicity.
Platelet to Lymphocyte Ratio) and Neutrophils to
Lymphocytes Ratio results indicate that the combination
treatment has better prognosis outcome than single
treatment and may become a potential alternative antitumor
treatment of breast cancer.
Synergistic anticancer effects of curcumin and
crocin on human colorectal cancer cells
Molecular Biology Reports | September 2022 Curcumin, a
polyphenol compound derived from the Curcuma longa L,
and crocin, a hydrophilic carotenoid from Crocus Sativus
Linnaeus, are traditionally used in food preparations in many
countries and could act as chemopreventive compounds against
several diseases, including cancer. Based on the obtained
results, curcumin and crocin treatment could cooperatively
reduce cell viability and induce apoptosis in SW-480 cells by
modulating the expression of Bax, Bcl-2, Caspase-3, Caspase-8,
Caspase-9, Jak2, Stat3, and Akt1 genes. Besides, curcumin and
crocin were able to synergistically increase the cell cycle
arrest at the sub G1 phase, induce autophagy and decrease the
clonogenic ability of SW-480 cells. These results suggested that
curcumin and crocin combination could be considered a more
effective therapeutic strategy for inhibiting colorectal cancer.
Curcumin against gastrointestinal cancer: A review
of the pharmacological mechanisms underlying its antitumor
activity Frontiers in Pharmacology |
September 2022 Gastrointestinal cancer poses a serious threat
to human health globally. Curcumin, a hydrophobic polyphenol
extracted from the rhizome of Curcuma longa, has shown reliable
anticancer function and low toxicity, thereby offering broad
research prospects. Numerous studies have demonstrated the
pharmacological mechanisms underlying the effectiveness of
curcumin against GIC, including the induction of apoptosis and
autophagy, arrest of the cell cycle, inhibition of the
epithelial–mesenchymal transition processes, inhibition of cell
invasion and migration, regulation of multiple signaling
pathways, sensitization to chemotherapy and reversal of
resistance to such treatments, and regulation of the tumor
survival environment. It has been confirmed that curcumin exerts
its antitumor effects on GIC through these mechanisms in vitro
and in vivo. Moreover, treatment with curcumin is safe and tolerable.
It has been reported that curcumin promoted pyroptosis in liver
cancer cells (Li W.-f. et al, 2021), induced necroptosis in
prostate and lung cancer cells (Lee et al., 2021), and induced
ferroptosis in breast (Li et al., 2020) and lung cancer cells
(Tang et al., 2021). Curcumin has exhibited good antitumor
activity and low toxicity. Newly discovered types of
regulated cell death, such as pyroptosis, necroptosis, and
ferroptosis, may provide a new direction for research on the
efficacy of curcumin against GIC. Curcumin is the most important
component of the rhizomes of turmeric (Curcuma longa) (Waly
et al., 2018). Curcumin is a hydrophobic polyphenol that has
been approved by the US Food and Drug Administration based on
its bio-safety (Mashayekhi-Sardoo et al., 2021). Moreover, it
has demonstrated a wide range of pharmacological activities,
such as antibacterial (Ibarra-Martinez et al., 2022),
anti-inflammatory (Yan et al., 2021), antioxidant (Xu et al.,
2021), and antitumor (Zhang et al., 2020). Curcumin has been
widely reported to inhibit the proliferation of tumor cells in a
concentration-and time-dependent manner in vitro (Li et al.,
2017a; Fan et al., 2020; Mao et al., 2021). In numerous studies,
curcumin, a plant extract with a good safety profile, has
exhibited pharmacological effects on GIC both in vivo and in
vitro. As demonstrated in the present review, curcumin can
effectively inhibit GlC through multiple targets, mechanisms,
and pathways.
Curcumin Remedies Testicular Function and
Spermatogenesis in Male Mice with Low-Carbohydrate-Diet-Induced
Metabolic Dysfunction International
Journal of Molecular Sciences | September 2022 Low
carbohydrate diet and ketogenic diet groups had significantly
lower testosterone concentrations than the normal diet group. In
contrast, the diet treated with curcumin supplementation group
had an increased testosterone concentration level. Curcumin
increases the testosterone level through upregulating 17β-HSD
expression. Curcumin, a powdered rhizome of Curcuma longa,
is considered a powerful antioxidant. The antioxidant capacity
of curcumin can be divided into the direct removal of reactive
oxygen species (ROS) and indirect activation of antioxidant
enzymes activities. These properties are related to the chemical
structure of curcumin, which includes bios-α, β-unsaturated
β-diketone, two methoxy groups, two phenolic hydroxy groups and
two conjugated bonds, which might play important roles in
anti-inflammatory and antiproliferative activities. A
randomized, double-blind, placebo-controlled clinical trial
showed that curcumin supplementation could increase sperm
quality, including total sperm count, sperm concentration and
motility, and improved the total antioxidant capacity of plasma,
malondialdehyde, C-reactive protein and tumor necrosis factor
(TNF). Curcumin, a phenolic compound extracted from the Curcuma
longa rhizome, has antioxidant, anti-inflammatory, and
anti-mutative properties. The present study shows that curcumin
improved the percentage of morphologically normal sperm and
testicular morphology. Alizadeh et al. showed that curcumin
could improve sperm count, concentration and motility in
patients with asthenoteratospermia. It is speculated that
curcumin, with a conjugated structure and an enol form, could
scavenge free radicals and increase the activity of antioxidant
enzymes, thereby improving sperm quality. The study shows that
oral curcumin (80 mg/kg) can lower lipid accumulation in liver
and adipose tissue and improve the insulin sensitivity of male
C57BL/6 mice with a 60% high-fat diet. Oral administration of
curcumin (80 mg/kg) in Sprague Dawley rats with a 60% high-fat
diet feeding showed anti-hyperglycemic, anti-lipolytic and
anti-inflammatory effects by attenuating TNF-α levels. In ICR
mice with spermatogenic disorders induced by scrotal heat
stress, administrating curcumin (80 mg/kg) by intragastric
intubation, also had antioxidative, anti-apoptotic and androgen
synthesis effects. Our results show that a
low-carbohydrate diet caused a lower sperm quality and a damaged
testicular histology. Administrating curcumin (80 mg/kg) could
partially reverse this condition. Mu et al. showed that
curcumin reversed high-fat-diet-induced decreased expressions of
Fas, Bax and cleaved caspase 3, and increased the expression of
Bcl-xl. In summary, the results of our study confirmed that a
low-carbohydrate diet led to a lower sperm quality and damaged
testicular histology. Supplementation with curcumin may improve
the impaired sperm and testis function via decreasing oxidative
stress, inflammation and apoptosis.
Anti-proliferation effects of apatinib in
combination with curcumin in breast cancer cells
Hormone Molecular Biology and Clinical Investigation | September
2022 The obtained results showed that all treatments of
apatinib, curcumin, and apatinib-curcumin significantly
decreased viability and proliferation of the breast cancer cells
in a concentration‐ and time‐dependent manner. Curcumin and
Apatinib-Curcumin increased apoptosis percentage in the treated
cancer cells through regulation of apoptosis-related genes
expression.
ERK1/2-Dependent Inhibition of Glycolysis in
Curcumin-Induced Cytotoxicity of Prostate Carcinoma Cells
BioMed Research International | September 2022 Curcumin
exerts chemotherapeutic effects on various types of cancers by
disrupting mitochondrial homeostasis and enhancing cellular
oxidative stress. Inhibition of ERK1/2 activation seems to serve
as an upstream event explaining the antiglycolytic and cytotoxic
roles of curcumin in prostate carcinoma cells preadapted to
acidic conditions. Numerous studies have shown that the growth
inhibitory effect of curcumin on various tumor cells is mediated
through actions on numerous molecules in the signaling pathway,
including p53, NF-κB, mitogen-activated protein kinases (MAPK),
Akt/mammalian target of rapamycin (mTOR), Notch-1, nuclear
factor erythroid 2-related factor 2 (Nrf2), Wnt/β-catenin, Janus
kinase (JAK)/signal transducer and activator of transcription
(STAT), and AMP-activated protein kinase (AMPK). Recently,
curcumin has been reported to suppress the Warburg effect in
various cancer cell lines by downregulating PKM2 expression
through inhibition of the mTOR/HIF-1α axis. In a previous study,
we reported the preferential cytotoxicity and mechanism of
curcumin on PC-3AcT cells that showed high resistance to
docetaxel, compared to parental PC-3 cells. Interestingly,
curcumin was shown to have the activity of co-inducing apoptosis
and necroptosis by increasing reactive oxygen species (ROS)
production and decreasing intracellular ATP content in human
prostate carcinoma cells preadapted to lactic acid-containing
media. Results provide mechanistic evidence for the
antiglycolytic and cytotoxic roles of curcumin through
inhibition of the MEK/ERK signaling pathway in prostate
carcinoma cells preadapted to acidic conditions. It is important
to note that curcumin promotes both apoptosis and necroptosis
for prostate cancer cells exhibiting the Warburg phenotype by
acting as a dual inhibitor of glycolysis and mitochondrial
function.
Piperine Enhances the Antimalarial Activity of
Curcumin in Plasmodium berghei ANKA-Infected Mice: A Novel
Approach for Malaria Prophylaxis
Evidence-Based Complementary and Alternative Medicine |
September 2022 Curcumin has numerous pharmacological,
antioxidant, anti-inflammatory, and anticarcinogenic activities.
Previous studies have reported the health beneficial effects of
dietary polyphenols, e.g., curcumin from turmeric for preventive
or therapeutic purposes in various types of cancer. Furthermore,
curcumin has well-known cytotoxic and parasiticidal effects on
protozoan parasites in vitro (e.g., Leishmania, Giardia,
Trypanosoma, and Plasmodium falciparum). Several studies have
shown the beneficial impacts of curcumin as an antimalarial
agent. For example, curcumin plays a role in disrupting
Plasmodium organelles such as apicoplast, microtubules, and
PfATP6 as well as affecting parasite chromatin modification
through HAT inhibition. In addition, curcumin may promote the
immune response against Plasmodium via increasing the reactive
oxygen species. Furthermore, curcumin inhibits glycogen synthase
kinase-3β (GSK3β), which affects the production of the
proinflammatory cytokines by inhibiting the transcriptional
activity of NF-κB. Nonetheless, the poor bioavailability of
curcumin due to expansive intestinal and hepatic metabolism
along with rapid elimination restricts its clinical use.
However, the absorption, distribution, metabolism, excretion,
and toxicity (ADMET) of a therapeutic could be achieved by
combining with bioenhancers like piperine. The combination
of piperine and curcumin can enhance the bioavailability of
curcumin in human and animal models. Recent studies
reviewed that the curcumin and piperine combination possibly has
prophylactic activity. The combination of curcumin and piperine
provided a good antimalarial activity with a synergistic effect
on Plasmodium berghei ANKA-infected mice, including inhibition
of parasitemia, delayed onset of clinical signs, and prolonged
survival rate. In addition, the low parasitic load in the liver,
lack of elevation in ALT and AST serum, and good
histopathological features of the liver suggest that piperine
may serve as a potential partner that can be combined with
curcumin as malaria prophylaxis.
Curcumin
improves the ability of donepezil to ameliorate memory
impairment in Drosophila melanogaster Drug
and Chemical Toxicology | September 2022 Curcumin and
donepezil, especially at lower dose of donepezil, significantly
improved the memory index and biochemical parameters compared to
donepezil alone. Thus, curcumin plus donepezil offers unique
therapeutic effects during memory impairment in the D.
melanogaster model of neurotoxicity.
Curcumin-mediated transcriptional regulation of
human N-acetylgalactosamine-α2,6-sialyltransferase which
synthesizes sialyl-Tn antigen in HCT116 human colon cancer cells
Frontiers in Molecular Biosciences | September 2022 Curcumin,
a natural polyphenolic compound, increases gene expressions of
ganglioside-specific human sialyltransferases, hST3Gal V and
hST8Sia I, in human cancer cell lines (Lee at al., 2018 a,
2018b). In this study, we investigated the effect of curcumin on
hST6GalNAc I gene expression in four kinds of human cancer cell
lines (colon cancer cell HCT116, lung cancer cell line A549,
glioblastoma cell line U-87 MG and breast cancer cell MCF-7). As
shown in Figure 1, gene expression of hST6GalNAc I assessed by
RT-PCR after treatment for 24 h with different concentration of
curcumin was increased remarkably in HCT116 cells, which began
to increase at 30 μM curcumin and showed about 14-fold
enhancement at 50 μM curcumin compared to untreated control
cells.
An examination of the protective effects and
molecular mechanisms of curcumin, a polyphenol curcuminoid in
diabetic nephropathy Biomedicine &
Pharmacotherapy | September 2022 The anti-inflammatory,
antioxidative, anti-apoptotic, and anti-fibrosis properties of
curcumin, a polyphenol curcuminoid, have been demonstrated in
research on diabetic nephropathy. Curcumin may have clinical
protective effects on diabetic nephropathy. Curcumin played
anti-inflammatory, antioxidant and anti-fibrosis effects in
diabetic nephropathy. Curcumin played anti-apoptosis and
promoted autophagy effects in diabetic nephropathy. Curcumin is
the most active ingredient of the curcuminoids and has been
shown to be safe and non-toxic in both pharmacological trials
and in vivo experiments. In addition, numerous studies have
demonstrated that curcumin exhibits positive biological
properties such as anticancer, anti-inflammatory, hypoglycemic,
antioxidant, and anti-apoptotic effects. Based on the remarkable
efficacy of curcumin, researchers have begun to focus on how it
can be applied to diabetes and its associated chronic
complications. Curcumin has been shown to play an essential role
in regulating hyperglycemia and lipid metabolism, alleviating
insulin resistance], inhibiting AGEs formation and AGEs-mediated
destruction, improving oxidative stress, inflammatory pathways
and apoptosis. Accumulating evidence indicates that curcumin
plays a vital role in the protection of multiple pathologic
mechanisms in diabetes retinopathy, diabetes cardiomyopathy and
diabetic neuropathy. Both clinical trials and preclinical
studies have verified that curcumin is beneficial to the
hypoglycemic process as well as insulin resistance improvement,
and more research on diabetic nephropathy has recently emerged.
A review of the underlying mechanisms of curcumin in diabetic
nephropathy examined its anti-inflammation, antioxidation,
anti-fibrosis, anti-apoptosis, and autophagy-promoting
properties. Notable progress has been made in preclinical
studies; however, clinical trials are still lacking. As a
natural polyphenol curcuminoid, curcumin is safe and effective
as a promising alternative therapeutic agent for the treatment
of diabetic mellitus and diabetic nephropathy.
The aphrodisiac potential of β-cyclodextrin–curcumin
via stimulating cAMP-PKA pathway in testicular Leydig cells
Nature | September 2022 Recent studies have confirmed the
potential pharmacological actions of curcumin in inflammatory
disorders, metabolic syndrome, cardiovascular disease, and
neurological disorders. Beyond these beneficial properties,
recent studies also revealed that curcumin potentially impacts
the reproductive system. Besides, curcumin was found to have
curative potential on the reproductive system function and its
impairment, regulated by stress and reproductive-related
hormones. Of note, researchers also demonstrated that curcumin
could increase spermatozoon motility in metronidazole-treated
mice.
Combined
Treatment with Curcumin and Ferulic Acid Suppressed the
Aβ-Induced Neurotoxicity More than Curcumin and Ferulic Acid
Alone International Journal of Molecular
Sciences | September 2022 Curcumin has been studied for its
antioxidant and anti-inflammatory effects. Curcumin is a
fat-soluble polyphenol abundant in turmeric, traditionally used
in Indian medicine. In some in vivo and in vitro studies,
curcumin has been found to have antioxidant and
anti-inflammatory effects, and it is therefore attracting
attention as a preventative action for Alzheimer’s disease by
inhibiting Aβ aggregation including oligomerization in vitro and
in vivo. Furthermore, the administration of curcumin to APPswe/PS1dE9
double transgenic mice has been found to reduce the γ-secretase
component presenilin-2 and promote the degradation of aggregated
Aβ.We find that combination treatment of curcumin and FA exerts
a cytoprotective effect on Aβ-induced cytotoxic effects, through
multiple mechanisms. These mechanisms include the suppression of
Aβ aggregation and antioxidant effects, as compared to single
treatment with either curcumin or FA alone. The protective
effects of the combination treatment we observed were
complementary and cooperative. These findings suggest that the
combination of curcumin and FA may provide an effective and
superior strategy for the prevention and therapeutics of
Alzheimer’s disease in humans.
Specific Irreversible Cell-Cycle Arrest and
Depletion of Cancer Cells Obtained by Combining Curcumin and the
Flavonoids Quercetin and Fisetin Genes |
September 2022 Curcumin treatment specifically triggers
senescence in cancer cells by inducing mitotic slippage and DNA
damage. We show that curcumin-induced senescence is
p21-dependent and characterized by heterochromatin loss.
Finally, we found that flavonoids clear curcumin-induced
senescent cancer cells. Our findings expand the characterization
of curcumin-induced cellular senescence in cancer cells and lay
the foundation for the combination of curcumin and flavonoids as
a possible anti-cancer therapy.
Curcumin and capsaicin regulate apoptosis and
alleviate intestinal inflammation induced by
Clostridioides difficile in
vitro Annals of Clinical Microbiology and
Antimicrobials | September 2022 Curcumin is found to possess
a wide array of biological features including anti-oxidant,
anti-tumor and also anti-inflammatory properties. Furthermore,
curcumin and its derivatives, bisdemethoxycurcumin and
demethoxycurcumin have been shown to exert antimicrobial
activities against different bacterial species particularly
multidrug resistant (MDR) strains. Curcumin has
anti-inflammatory and also anti-fibrosis effects by suppressing
the NF-κB and TGF-β1/SMAD-3 signaling pathways, respectively.
Vasanthkumar et al. demonstrated that curcumin and CAP alone or
in combination cause considerable reduction in LPS-induced
overexpression of COX-2, IL-6 and TGF-β. Consistent with
previous studies, findings of the present work revealed that
curcumin could decrease the C. difficile-induced gene
expression level
The Regenerated Capacity of Curcumin in the
Migration of Epidermal Stem Cells Promotes Skin Wound Healing in
a Wistar Rat International Journal of
Pharmacology | September 2022 Turmeric contains a polyphenol
called curcumin, which is similar to stem cells in that it can
renew identical cells and preserve proliferation and
multipotency. Curcumin’s anti-inflammatory and stemness
properties as well as regenerative benefits, were investigated
in this study. The curcumin decreased granulation tissue
intensity vs. the control group on days 7 and day 14. Curcumin
significantly reduced the mean of angiogenesis vs. the
negative-control group. However, curcumin significantly improves
epidermal thickening vs. the negative-control group (score 1 vs.
2, p<0.05), respectively at days 21 and 28. Curcumin improves
the collagen fibre, on day 21 as fascicle vs. mixed when
compared to the negative-control group. While, on days 21 and 28
the mature collagen was profoundly deposited vs. moderately in
the curcumin vs. control groups. Conclusion: we conclude that
curcumin significantly accelerated the healing course via
modulation in the amount, maturation and arrangement of collagen
fibre. Curcumin had a putative regenerative property upon
upregulation of CD34 as epidermal stem cell marker expression in
epidermis and hair follicles.
Cocktail of isobavachalcone and curcumin enhance
eradication of Staphylococcus aureus biofilm from orthopedic
implants by gentamicin and alleviate inflammatory osteolysis
Microbiology | September 2022 The combination of
isobavachalcone and curcumin can enhance the susceptibility of
MRSA to gentamicin, thus promoting the eradication of MRSA
biofilm. When administrated as cocktail in vivo, they can
significantly modify local inflammation in orthopedic
device-related infection and maintain trabecular bone
microstructure while substantially eradication MRSA in ODRI.
Although our current study did not reveal specific mechanism
about the synergy of this cocktail of gentamicin,
isobavachalcone and curcumin against S. aureus, their bone
microarchitecture maintenance characteristic did provide us the
insight and evidence for future potential topical application by
incorporating the mixture of these two small molecules with
conventional antibiotics, like gentamicin bone cement chain
beads and antimicrobial biomaterials, etc. The combination of
isobavachalcone and curcumin as adjuvants administrated together
with gentamicin to significantly enhance its antimicrobial
effect, which may serve as a new potential treatment strategy
especially for MRSA-induced ODRI, to rationalize the use of
high-level antibiotics and reduce the emergence of
drug-resistant strains of bacteria.
Curcumin and Curcuma longa Extract in the Treatment
of 10 Types of Autoimmune Diseases: A Systematic Review and
Meta-Analysis of 31 Randomized Controlled Trials
Frontiers in Immunology | August 2022 Curcumin and Curcuma
longa Extract had good clinical efficacy in the treatment of
psoriasis, ulcerative colitis and rheumatoid arthritis, so
Curcumin and Curcuma longa Extract could be used in the
treatment of the above diseases in the future. Curcumin is the
most effective ingredient extracted from the rhizomes of ginger
plants such as turmeric. A number of in vitro and in vivo
experiments showed that Curcumin has various pharmacological
effects such as regulating immunity, anti-oxidation, inhibiting
inflammation, anti-tumor, anti-angiogenesis, anti-coagulation,
and scavenging free radicals. These studies suggest that
Curcumin may play a regulatory role by altering the activities
of enzymes, receptors, and related transcription factors.
Numerous randomized controlled trials have shown that curcumin
can alleviate many human diseases, including autoimmune
diseases, with the main mechanisms in regulating immunity and
inhibiting inflammation. Also, Curcumin is administered with few
side effects, making it a potential alternative to NSAIDs and
other drugs with known severe side effects. Curcumin has been
shown to be a potent immunomodulator, which can modulate the
activity of T cells, B cells, macrophages, neutrophils, NK
cells, and dendritic cells. The diverse pharmacological
activities of Curcumin stem from its ability to interact with
different biological targets and signaling pathway.
Current pharmacological studies have shown that Curcumin and
Curcuma longa Extract seems to reverse some clinical symptoms of
many autoimmune diseases by regulating immune inflammatory
biological modules, such as inflammatory factors and immune
inflammatory cell activation, differentiation and immune
function regulation. Curcumin and Curcuma longa Extract is an
effective natural compound with a variety of therapeutic
pharmacological properties and almost no side effects. Recent
studies have shown that curcumin can synergistically enhance the
synergistic effect of glucocorticoids and alleviate
glucocorticoid-induced osteoporosis. Because of its good
clinical safety, the dose of curcumin in the treatment of
autoimmune diseases is mainly between 80 mg and 6000 mg. The
results of Meta-analysis showed that Curcumin and Curcuma longa
Extract had good clinical efficacy in the treatment of
Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract
could be used in the treatment of the above diseases in the
future.
Protective and anti-oxidative effects of curcumin
and resveratrol on Aβ-oligomer-induced damage
Journal of the Neurological Sciences | August 2022 Results
suggest that curcumin and resveratrol decreased ROS generation,
attenuated oxidative stress, inhibited tau hyperphosphorylation,
and protected SH-SY5Y cells from AβO damage. Both curcumin and
resveratrol are promising supplements or medicine as therapeutic
agents for the treatment of Alzheimer's disease.
Curcumin Suppresses the Progression of Colorectal
Cancer by Improving Immunogenic Cell Death Caused by Irinotecan Chemotherapy
Anticancer Section | August 2022 Curcumin, an adjuvant drug
with anti-inflammatory and antitumor effects, has been studied
extensively, although its synergistic antitumor effect remains
unclear. Results: Irinotecan in combination with curcumin had
synergistic antitumor effects in CT-26 colon carcinoma cells.
Combination treatment with Irinotecan and curcumin was more
effective than Irinotecan or curcumin alone. Irinotecan and
curcumin combination treatment significantly upregulated
ICD-related proteins including CALR and HMGB1 and had a greater
antitumor effect than Irinotecan or curcumin single treatment in
vivo. Curcumin may synergistically improve the antitumor effect
of Irinotecan by promoting the ICD effect. Conclusion:
Combination therapy with Irinotecan and curcumin may be an
option for first-line chemotherapy in some patients with
advanced colorectal cancer.
Effects
and Mechanisms of Curcumin for the Prevention and Management of
Cancers: An Updated Review Antioxidants |
August 2022 Curcumin possesses various biological activities,
such as antibacterial, anti‐inflammatory, antioxidant and
anticancer effects. Curcumin has shown anticancer effects on
various cancers, such as breast, liver, lung, gastric and
prostate cancers. For example, curcumin inhibited breast cancer
cells proliferation and induced apoptosis by increasing reactive
oxygen species (ROS) production. Curcumin also inhibited liver
cancer. Curcumin has been selected as a third‐generation cancer
chemopreventive agent by the National Cancer Institute. The
anticancer effects of curcumin have been extensively studied in
different cancers, such as breast, lung, colorectal, head and
neck, gastric, bladder, prostate, thyroid, liver, ovarian, oral,
pancreatic, cervical, tongue and brain cancers. Many studies
have reported the effectiveness of curcumin in the prevention
and management of various cancers, such as thyroid, breast,
gastric, colorectal, liver, pancreatic, prostate and lung
cancers. The potential mechanisms include inhibiting cancer cell
proliferation, suppressing invasion and migration, promoting
cell apoptosis, inducing autophagy, decreasing cancer stemness,
increasing reactive oxygen species production, reducing
inflammation, triggering ferroptosis, regulating gut microbiota,
and adjuvant therapy.
Curcumin activates autophagy and attenuates high
glucose‑induced apoptosis Experimental and
Therapeutic Medicine | August 2022 Curcumin is well known for
its anti‑inflammatory and antioxidant effects. Accumulating
evidence suggests that curcumin can act as an agent with
anti‑inflammatory, antioxidant, anticarcinogenic and
antilipidemic effects. Curcumin can improve gastric emptying in
rats by blocking the production of oxidative stress. In
addition, curcumin also induces autophagy to protect the
vascular endothelial cells and reduces the cell apoptosis from
the oxidative stress damage, suggesting a potential mechanism
underlying the anti‑apoptosis effects of curcumin. Overall,
previous studies have confirmed that curcumin has a strong
antioxidant and antiapoptosis effect. Curcumin alleviated
apoptosis by promoting autophagy and inhibiting the ROS/NF‑κB
signaling pathway.
Identifying the Antitumor Effects of Curcumin on
Lung Adenocarcinoma Using Comprehensive Bioinformatics Analysis
Drug Design, Development and Therapy | July 2022 The results
of this study suggest that the therapeutic effects of curcumin
on Lung Adenocarcinoma may be achieved through the intervention
of INS and GCG, which may act as potential biomarkers for Lung
Adenocarcinoma prevention and treatment. Curcuma longa L.,
also known as turmeric, has been widely used as a traditional
medicine in China, India, and Southeast Asia. As the main
component of turmeric, curcumin was first used to treat
cholecystitis in 1937. Curcumin mediates its anticancer activity
by modulating molecular targets including transcription factors,
micro-RNAs, cytokines, and interfering with genes related to
apoptosis and proliferation—thus inhibiting tumor cell
proliferation and migration, inhibiting angiogenesis, inducing
apoptosis, and increasing sensitivity to antitumor therapy. Due
to its excellent pharmacological activity, curcumin is widely
used in the treatment of many diseases, including
gastrointestinal disease, liver cirrhosis, cardiovascular
disease, diabetes, and cancer. Increasing studies suggest that
curcumin inhibits the growth of lung cancer cells through
multiple pathways by inducing apoptosis, inhibiting cell
proliferation, and epigenetic changes. These studies have
indicated that curcumin has great potential in the treatment of
various diseases. We found that curcumin significantly inhibited
the proliferation, migration and invasion of Lung Adenocarcinoma
A549 and NCI-H1299 cells and significantly decreased the
expression of INS and GCG genes.
Curcumin
reduces blood-nerve barrier abnormalities and cytotoxicity to
endothelial cells Folia Morphologica | July
2022 Curcumin, a polyphenol found in the root of Curcuma
longa, had favorable effects on cisplatin neuropathy in
previous work. Curcumin alleviated pericyte detachment,
cytotoxicity, oxidative stress, TEER reduction and tight
junction protein expression. Curcumin might improve neuropathy
via the restoration of BNB. Whether alterations in the BNB occur
and curcumin is effective in patients with cisplatin neuropathy
remain to be investigated.
The protective effect of curcumin on testicular
tissue in a cryptorchid rat model
Journal of Pediatric Urology | July 2022
Curcumin administration ameliorated the histological appearance
of the testis and greatly reduced the level of apoptosis in
cryptorchidism rats' testicular cells. After curcumin treatment,
the expression of proliferating cell nuclear antigen (PCNA) was
restored in the testis tissues of cryptorchidism rats. Curcumin
therapy reduced Bax expression while increasing Bcl-2
expression, according to the molecular study. Curcumin therapy
also reduced malondialdehyde (MDA) levels and enhanced
superoxide dismutase (SOD) levels in cryptorchidism rats' testis
tissue.
Exploring the Mechanism of Curcumin on
Retinoblastoma Based on Network Pharmacology and Molecular
Docking Evidence-Based Complementary and
Alternative Medicine | July 2022 Curcumin shows great effects
of inhibiting tumor cell proliferation, inducing apoptosis,
inhibiting tumor metastasis, and inhibiting angiogenesis on a
variety of tumors. Curcumin is a yellow phenolic pigment with
low toxicity, wide medicinal source and low price extracted from
the rhizome of Curcuma longa of the ginger family, such as
turmeric, which has a wide application prospect and value in
clinical treatment. We initially revealed that curcumin exerts
its therapeutic effects on retinoblastoma with multitarget,
multipathway, and multibiological functions, providing a
theoretical basis for subsequent studies. In conclusion, this
comprehensive network-based pharmacological analysis suggests a
number of testable speculations on the potential molecular
mechanisms of curcumin in the treatment of retinoblastoma and
predicts RB1, STAT3, and CDKN2A as potential therapeutic
targets.
Curcumin, thymoquinone, and 3, 3′-diindolylmethane
combinations attenuate lung and liver cancers progression
Frontiers in Pharmacology Sec. Ethnopharmacology | July 2022
Results showed that triple (Curcumin + TQ + DIM) and
double (Curcumin + TQ, curcumin + DIM, and TQ + DIM) combinations of
Curcumin, TQ, and DIM significantly increased apoptosis with
elevation of caspase-3 protein levels. Also, these combinations
exhibited significantly decreased cell proliferation, migration,
colony formation activities, phosphatidylinositol 3-kinase
(PI3K), and protein kinase B (AKT) protein levels with S phase
reduction. Triple and double combinations of Curcumin, TQ, and
DIM hindered tumor weight and angiogenesis of A549 and HepG2
implants in the chorioallantoic membrane model. Interestingly,
Curcumin, TQ, and DIM combinations are considered promising for
suppressing cancer progression via inhibiting tumor
angiogenesis. Curcumin, the active ingredient of Curcuma
longa L is the most studied compound described as a
potential anticancer agent due to its multi-targeted
signaling/molecular pathways (Sharma and Martins, 2020; Shah et
al., 2021). Generally, Curcumin has the highest binding
affinities with target proteins, followed by DIM and then TQ.
Furthermore, because Curcumin, TQ, and DIM have different and
common targets, we suggest treating different cancer cells. In
the same context, we encourage researchers to investigate
Curcumin, TQ, and DIM combination with chemotherapeutic agents
investigating the effect of natural products combined with
commonly used chemotherapeutics for cancer therapy.
Curcumin Alleviates D-Galactose-Induced
Cardiomyocyte Senescence
Natural Products and Herbal Medicine: Safety,
Efficacy, and Bioactivity | July 2022 Curcumin could be an
effective anticardiac aging drug. The polyphenolic compound
curcumin is derived from turmeric and possesses therapeutic and
biological properties against many human health issues.
Experiments in vitro and in vivo suggest that curcumin could
prevent cardiovascular diseases, alleviate cardiovascular aging,
and induce autophagy via various signaling pathways, including
SIRT, AMPK, and mTOR. Curcumin has antioxidant,
autophagy-promoting, and antiaging properties. The polyphenol
compound, curcumin, extracted from turmeric, has various
therapeutic uses in humans. It induces antioxidant,
anti-inflammatory, anticancer, and antiaging effects. Curcumin
protects against cardiovascular diseases, such as cardiac
hypertrophy, heart failure, and atherosclerosis. The role of
curcumin in regulating apoptosis and autophagy is well-studied,
including its role in reversing the aging process and reducing
oxidative stress. Curcumin ameliorates aging by promoting
autophagy and reducing oxidative stress during oxidative
stress-induced cardiac aging. These protective effects of
curcumin in cardiac aging is consistent with the interaction
between autophagy and oxidative stress. In addition, curcumin
could be used as a potential pharmacological candidate for
treating cardiac aging. Curcumin alleviated cardiac aging by
promoting autophagy and reducing oxidative stress in vivo. The
experimental results also revealed that curcumin acted as a
cardioprotective agent.
The Effect of Curcumin on Lipid Profile and Glycemic
Status of Patients with Type 2 Diabetes Mellitus: A Systematic
Review and Meta-Analysis Evidence-Based
Complementary and Alternative Medicine | July 2022 Curcumin
supplementation had beneficial effects on glycemic status and
some lipid parameters in patients with type 2 diabetes mellitus
(T2DM). Curcumin has a wide range of pharmacological
effects, including antioxidant, anti-inflammatory,
antibacterial, antiviral, antifungal, and antitumor properties.
Experimental and clinical studies also have reported the
beneficial effects of curcumin supplementation on lipid profile
and glycemic status. In conclusion, this meta-analysis
provided evidence that curcumin has promising effects on the
lipid profile and glycemic status in patients with T2DM. It
indicated that curcumin might be a favorable therapeutic option
for T2DM patients with mixed dyslipidemia.
Curcumin
attenuates development of depressive-like behavior in male rats
after spinal cord injury: involvement of NLRP3 inflammasome
Journal of Contemporary Medical Sciences | July
2022 Curcumin appears to constitute a suitable agent to
reduce neuroinflammation and through it, relieve a
depressive-like state. Curcumin is a multifunctional drug
and it has a lot of pharmacologic effects, like
anti-inflammatory, anti-oxidant, and anti-infectious activities.
Studies have reported that curcumin improves neurological
defects by inhibiting apoptosis and neuronal cell death and
reducing inflammation. Considering the role of curcumin in
reducing inflammation after spinal-cord injury and the role of
NLRP3 inflammasome in starting of inflammation and also the role
of the inflammatory process in depression after spinal-cord
injury, the purpose of this study is investigating curcumin role
in mood alterations in male rats after spinal-cord injury
through focusing on the involvement of NLRP3 inflammasome. Our
results suggested that administration of curcumin
decreased neuroinflammation. Based on the findings of the
behavioral tests in the present study, because of safety and
high ability to enhance the parameters related to depression,
curcumin can be considered as a treatment for depression.
The
Role of Curcumin in Prostate Cancer Cells and Derived Spheroids
Cancers | July 2022 Curcumin can
suppress the proliferation of both androgen-dependent and
androgen-independent PC cell lines. Consequently, curcumin
administration seems to be useful in PC prevention, and in
co-treatment with conventional therapy to halt PC progression
towards mCRPC. Despite its widely reported health benefits, the
use of curcumin is hampered by its poor bioavailability which
limits its clinical application. In this regard, several
strategies were developed to overcome these limitations,
including improving the delivery system by encapsulating
curcumin in the form of nanoparticles, designing novel
structural analogs, and liposomal encapsulation and emulsions.
Our study provides evidence that curcumin supplementation can be
used as a preventative strategy and opens up new frontiers for
further studies aimed at implementing the diet with
nutraceuticals. In conclusion, despite different studies being
carried out to identify the potential synergistic curcumin
combinations with chemopreventive/therapeutic ef ficacy for
inhibiting PC growth, to our knowledge, this study is the first
to show the ability of curcumin used alone or in combinatorial
approaches to impair the size and the viability of PC-derived
spheroids.
Therapeutic Potential of Curcumin and its
Derivatives on Brain Tumor Glioma Biology
Neurochemical Research | July 2022 Curcumin is a natural
polyphenolic compound with several anti-tumor effects which
potentially inhibit tumor growth, development, proliferation,
invasion, dissemination, and angiogenesis in different human
malignancies. Experimental model studies have demonstrated that
curcumin attenuates glioma cell viability by G2/M cell cycle
arrest, apoptosis, induction of autophagy, gene expression
alteration, and disruption of multi-molecular pathways.
Moreover, curcumin has been reported to re-sensitize cancer to
chemotherapeutics as well as augment the effect of radiotherapy
on glioma cells. In this review, we have provided an update on
the in vitro and in vivo effects of curcumin-based therapy on
gliomas. We have also discussed the use of curcumin in
combination therapies, its effectiveness on drug-resistant
cells, and new formulations of curcumin in the treatment of
gliomas.
The Effect of Curcumin on Lipid Profile and Glycemic
Status of Patients with Type 2 Diabetes Mellitus: A Systematic
Review and Meta-Analysis Evidence-Based
Complementary and Alternative Medicine | July 2002 Curcuma
longa L. is a traditional medicinal plant, which is widely
distributed in China and some Asian countries. Turmeric, the
rhizome of Curcuma longa L, is used as a spice to
improve taste and also as medicine because of its therapeutic
properties. Curcuminoids, the main bioactive agents extracted
from the rhizome of Curcuma longa L, is responsible for
the major biological effects of turmeric. As the main present
form of curcuminoids, curcumin has a wide range of
pharmacological effects, including antioxidant,
anti-inflammatory, antibacterial, antiviral, antifungal, and
antitumor properties. Experimental and clinical studies also
have reported the beneficial effects of curcumin supplementation
on lipid profile and glycemic status. The results of this study
showed that curcumin supplementation had beneficial effects on
glycemic status and some lipid parameters in patients with Type
2 diabetes mellitus. In conclusion, this meta-analysis provided
evidence that curcumin has promising effects on the lipid
profile and glycemic status in patients with Type 2 diabetes
mellitus. It indicated that curcumin might be a favorable
therapeutic option for Type 2 diabetes mellitus patients with
mixed dyslipidemia.
The
Effect of Curcumin on Renal Ischemia/Reperfusion Injury in
Diabetic Rats Nutrients | July 2022
Curcumin has shown to be effective in the regulation of glycemia
and lipidemia with an action mechanism similar to antidiabetic
medications. In addition, recent studies have demonstrated
promising effects of curcumin for the treatment of autoimmune
diseases, such as type 1 diabetes. It has been also demonstrated
that it could have a potential role in preventing and treating
several diseases due to its antibacterial, antiviral,
anti-ischemic, hepatoprotective, nephroprotective, antirheumatic
and anticancer activities. his study proved the effectiveness of
curcumin as a renoprotective agent in DM with I/R, becoming a
promising agent for the suppression of the morbidity of DM. In
addition, the study suggests that, after other preclinical
studies with different formulations and administration routes
designed to obtain products with higher bioavailability, with a
larger sample and other methodologies for evaluating renal
function and also clinical studies, curcumin can be considered a
therapeutic possibility to be incorporated into the clinical
treatment of diabetic patients at risk for complications of
renal function. Early treatment with curcumin improved renal
function in diabetic rats submitted to I/R with beneficial
repercussions on renal hemodynamics and renal oxidative profile.
Curcumin as a Promising Neuroprotective Agent for
the Treatment of Spinal Cord Injury: A Review of the Literature
Neurospine | July 2022 Curcumin is a promising therapeutic
drug for spinal cord injuries (SCIs)treatment because it
reduces the incidence of secondary injuries. Curcumin has
antioxidant and nonsteroidal anti-inflammatory pharmacological
properties. Preclinical and clinical trials have revealed its
various pharmacological activities, including its
anti-inflammatory, antibacterial, anticancer, and
neuroprotective effects on neurodegenerative disorders. Curcumin
also has hepatoprotective, nephroprotective, cardioprotective,
neuroprotective, hypoglycemic, and antirheumatic activities, and
its neuroprotective activity against several neurodegenerative
disorders is gaining researchers’ attention. As an
anti-inflammatory agent, curcumin suppresses the production of
many proinflammatory cytokines, including tumor necrosis
factor-alpha (TNF-α), interleukin (IL)-1, IL-8, and monocyte
chemoattractant protein 1 [8,9]. In a recent study, curcumin
inhibited the hypoxia-induced upregulation of glial fibrillary
acidic protein (GFAP) and neurofilament-H following hypoxia and
downregulated the expression of proinflammatory cytokines, such
as TNF-α and IL-1. It also suppresses glial scar formation and
GFAP expression, contributing toward the development of a more
favorable environment for neurological recovery. Curcumin is a
neuroprotective polyphenolic compound that has benefits such as
pluripotency, oral safety, long usage history, and low cost.
Several animal experiments have shown that curcumin can minimize
secondary injury following primary SCIs through its
anti-inflammatory, antioxidant, and stem cell mobilization
properties. Curcumin is an influential therapeutic agent that
can potentially treat catastrophic secondary injuries in the
spinal cord, including inflammation, edema, free radical injury,
fibrosis, and glial scar formation. It can enhance neurological
function in rats, as measured using the BBB locomotor rating
scale.
Antioxidant Potential of Phytoconstituents with Special
Emphasis on Curcumin Antimicrobial and
Pharmacological Aspects of Curcumin | July 2022 The medicinal
properties of turmeric, the source of curcumin, have been known
for thousands of years; however, the ability to determine the
exact mechanism(s) of action and to determine the bioactive
components have only recently been investigated. Curcumin
(1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione),
also called diferuloylmethane, is the main natural polyphenol
found in the rhizome of Curcuma longa (turmeric).
Curcumin, a polyphenol, has been shown to target multiple
signaling molecules while also demonstrating activity at the
cellular level, which has helped to support its multiple health
benefits such as antioxidant, anti-inflammatory, antimutagenic,
antimicrobial and anticancer properties.
Curcumin improves D-galactose and normal-aging
associated memory impairment in mice: In vivo and in
silico-based studies Plos One | July 2022
Curcumin, a natural flavonoid, has potent antioxidant and
anti-aging properties. Curcumin significantly increased
retention time (p < 0.05) and freezing response (p < 0.05) in PA
and CFC, respectively. Curcumin profoundly ameliorated the
levels of glutathione, superoxide dismutase, catalase, advanced
oxidation protein products, nitric oxide, and lipid peroxidation
in mice hippocampi. In silico studies revealed favorable binding
energies of curcumin with GSTA1, GSTO1, KEAP1, BACE1, and MAOA.
Curcumin improves retention and freezing memory in D-gal and
nature-induced aging mice. Curcumin ameliorates the levels of
oxidative stress biomarkers in mice. Anti-aging effects of
curcumin could be attributed to, at least partially, the
upregulation of antioxidant enzymes through binding with GSTA1,
GSTO1, KEAP1, and inhibition of oxidative damage through binding
with BACE1 and MAOA. We investigated the detailed effects of
curcumin on oxidative stress in the D-gal and nature-induced
aging mice model. Our in vivo study suggested that curcumin
improves memory and rescues learning impairment by modulating
oxidative stress levels. Furthermore, our in-silico study
demonstrated that curcumin has good binding affinities for
several molecular targets implicated in redox homeostasis.
Finally, based on our in vivo and computational studies, it can
be stated that curcumin improves aging-associated memory
impairment by reducing oxidative overload in mice.
Effects of curcumin on low-density lipoprotein (LDL)
oxidation from experimental studies to clinical practice
Excli journal | July 2022 Curcumin is a potent antioxidant
and has a strong track record in the treatment of numerous
diseases. Recent studies indicate that Curcumin exerts a
lipid-lowering effect, and can modulate the formation of
atherosclerotic plaque. Curcumin has a long history in the
treatment of diseases, such as gastric and hepatic disorders,
dental problems, menstrual difficulties, infectious diseases,
malignancies, immune-related and metabolic disorders (Sahebkar
and Henrotin, 2016; Panahi et al., 2017; Bagherniya et al.,
2018; Parsamanesh et al., 2018; Gorabi et al., 2019; Mortezaee
et al., 2019; Shakeri et al., 2019; Zahedipour et al., 2020;
Afshari et al., 2021; Fu et al., 2021; Mohammed et al., 2021).
Anti-inflammatory and antioxidant properties of Curcumin, a
polyphenol, have been reported in numerous studies (Menon and
Sudheer 2007; Shehzad et al., 2011; Momtazi-Borojeni et al.,
2018; Farhood et al., 2019). Curcumin can improve the lipid
profile of patients by reducing serum triglyceride (TG), LDL and
total cholesterol levels significantly in subjects with coronary
artery disease. Curcumin decreases the aortic lipid lesions and
inhibits development of atherosclerotic plaques (Wongcharoen and
Phrommintikul 2009). Curcumin demonstrates antioxidant activity
because the benzene rings in the structure of the Curcumin
molecule eliminate reactive oxygen species (ROS) (Joe and Lokesh,
1994). According to cardiac-related studies, serum levels of
lipid peroxides are higher in patients with IHD; Curcumin is
able to reduce lipid peroxide concentration (Stringer et al.,
1989; Soni and Kuttan 1992). These actions could indicate that
curcumin also inhibits ox-LDL elevation. Overall, our results
suggest that curcumin could be effective in reducing LDL
oxidation.
Curcumin inhibits the replication of rotavirus in
vitro Acta Virologica | July 2022 The
present study aims to determine the effect of curcumin, a
natural polyphenol compound, on rotavirus in a cell culture
model. The anti-viral activity of curcumin was evaluated by
reverse-transcriptase quantitative PCR (RT-qPCR), TCID50, and
western blot techniques to assess CC50 in curcumin-treated MA104
cells as well as EC50 and SI within the infected MA104 cell
line. Our findings supported that curcumin exerted an inhibitory
influence against rotavirus in a dose-dependent manner and
decreased the viral titer and VP6 expression by ~99% at a
concentration of 30 μM.
How
Curcumin Targets Inflammatory Mediators in Diabetes: Therapeutic
Insights and Possible Solutions Molecules
| July 2022 Curcumin, a polyphenol derived from turmeric, is
well known for its anti-oxidant, anti-inflammatory, and
anti-apoptotic properties. Curcumin’s anti-inflammatory and
anti-oxidative activities against a wide range of molecular
targets have been shown to have therapeutic potential for a
variety of chronic inflammatory disorders, including diabetes.
Curcumin’s biological examination has shown that it is a
powerful anti-oxidant that stops cells from growing by releasing
active free thiol groups at the target location. Curcumin is a
powerful anti-inflammatory agent that targets inflammatory
mediators in diabetes, and its resistant form leads to better
therapeutic outcomes in diabetes complications. Moreover,
Curcumin is an anti-oxidant and NF-B inhibitor that may be
useful in treating diabetes. Curcumin has been shown to inhibit
diabetes-related enzymes, such as a-glucosidase, aldose
reductase and aldose reductase inhibitors. Through its
anti-oxidant and anti-inflammatory effects, and its suppression
of vascular endothelial development and nuclear transcription
factors, curcumin has the ability to prevent, or reduce, the
course of diabetic retinopathy. Curcumin improves insulin
sensitivity by suppressing phosphorylation of ERK/JNK in
HG-induced insulin-resistant cells and strengthening the
PI3K-AKT-GSK3B signaling pathway. Curcumin is an anti-oxidant
and NF-κB inhibitor that may be useful in preventing and
treating diabetes. Curcumin has been shown to inhibit
diabetes-related enzymes, such as a-glucosidase, aldose
reductase, and aldose reductase inhibitors . Curcumin has been
shown to have therapeutic potential in the prevention, or
delaying, of diabetic retinopathy, by acting as an anti-oxidant
and an anti-inflammatory, and inhibiting vascular endothelial
development and nuclear transcription factors. Curcumin’s
current applications for glycemia and diabetes-related liver
illnesses, neuropathy, adipocyte dysfunction, vascular diseases,
nephropathy, and pancreatic disorders were described in.
Curcumin has shown efficient anti-inflammatory, anti-apoptotic
and anti-oxidant potential. In patients with metabolic syndrome,
short-term treatment with a curcuminoid-piperine combination
reduced inflammatory status dramatically. Curcuminoids are
effective, safe and natural CRP-lowering compounds. In addition,
curcumin reduces levels of inflammatory mediators and factors,
such as TNF-α, INF-γ, reduces systemic inflammatory biomarkers.
such as RANTES. and other cytokine levels. Curcumin also reduces
the levels of inflammatory cytokines, such as IL-6 and IL-1β,
and targets inflammatory mediators in insulin diabetes
resistance. Curcumin restores dysfunction associated with Nrf2
that helps in diabetes resistance management. Similarly,
curcumin inhibits inflammatory signaling and the expression of
Kelch-like ECH-associated protein 1 (Keap1), resulting in
activation of the Nrf2 system. Curcumin metabolites have shown
significant results in diabetes mellitus treatment focusing on
inflammatory mediators.
Curcumin Increased the Sensitivity of Non-Small-Cell
Lung Cancer to Cisplatin through the Endoplasmic Reticulum
Stress Pathway Evidence-Based Complementary
and Alternative Medicine | July 2022 Curcuma longa was reported to
possess antitumor activity through regulating oncogene
expression, cell cycle regulation, apoptosis, tumorigenesis, and
metastasis. Recently, curcumin was found to promote
chemotherapeutic efficiency in various cancers and diseases. For
instance, Zou et al. reported that curcumin increases breast
cancer cell sensitivity to cisplatin by decreasing FEN1
expression. Lu et al. found that curcumin can increase the
sensitivity of paclitaxel-resistant non-small-cell lung cancer
cells to paclitaxel through microRNA-30c-mediated MTA1
reduction. Recently, curcumin was found to increase effects of
irinotecan through mediating the ER stress pathway in colorectal
cancer cells. Misra et al. found that curcumin regulates ER
stress through cAMP responsive element-binding protein H.
Curcumin can enhance the chemosensitizing effect of
non-small-cell lung cancer cells by targeting the ER stress
pathway. Taken together, this study demonstrated curcumin can
increase DDP sensitivity of non-small-cell lung cancer cells
through mediating the ER stress pathway. The results of this
study proposed a possible mechanism of curcumin improving DDP
sensitivity in non-small-cell lung cancer cells and may shed a
little light on developing the molecular targets in the ER
stress pathway to overcome the DDP resistance in non-small-cell
lung cancer.
Curcumin and metformin synergistically modulate
peripheral and central immune mechanisms of pain
Scientific Reports | June 2022 Curcumin is a
natural polyphenol and has beneficial therapeutic effects on
pain. Curcumin has been used as an analgesic adjuvant with
several analgesic drugs, allowing synergistic antinociceptive
effects. Coadministration of curcumin and metformin at a 1:1
fixed ratio of their ED50 doses significantly reduced the dose
required to produce a 50% effect compared to the theoretically
required dose in phase II of the formalin test with a
combination index value of 0.24. Our findings suggest that
curcumin exerts synergistic anti-inflammation with metformin
with no potential CNS adverse effects. Curcumin has been used as
a traditional herbal remedy for centuries throughout Asia due to
its pleiotropic activities, including anti-inflammatory,
antioxidant, and anticancer. It is a well‐tolerated natural
product causing no or minimal toxicity in short- and long-term
use. Consequently, it was declared “generally recognized as
safe” by the US Food and Drug Administration (FDA)21. Moreover,
the therapeutic effectiveness of curcumin in nociceptive,
inflammatory, and neuropathic pain has been reported in numerous
animal models and humans. Dual treatment with curcumin and
metformin has been reported in diabetic mellitus,
diabetes-induced comorbidities, nephrotoxicity, hepatocellular
carcinoma, pancreatic cancer cells, and breast cancer, with the
results suggesting synergistic effects. Moreover, metformin and
curcumin have different mechanisms of action in pain modulation,
which indicates the potential for exerting greater analgesia
when administered together. In summary, this study
suggests for the first time that curcumin combined with
metformin exerts synergistic anti-inflammatory effects in both
in vitro and in vivo conditions. Curcumin synergistically
augmented the inhibition of nitric oxide and proinflammatory
cytokines by metformin both in RAW 264.7 macrophage and BV-2
microglial cells. Moreover, the combined therapy using
curcumin and metformin showed no considerable CNS adverse
effects in naïve mice. Hence, this study supports the
possibility of combined use of curcumin and metformin in the
treatment of pain with the least amount of medication while
taking the easiness of administration, cost of the therapy, and
side effect profile of medicines into the account.
Combined
Curcumin and Luteolin Synergistically Inhibit Colon Cancer
Associated with Notch1 and TGF-β Signaling Pathways in Cultured
Cells and Xenograft Mice
Cancers | June 2022 A combination of luteolin
(30 µM) and curcumin (15 µM) was selected as the optimum
combination for the study due to a low combination index of 0.25
and its highest synergistic inhibitory effect on the growth of
two human colon cancer cell lines CL-188 and DLD-1. Consistent
with in vitro results, intraperitoneal injection of luteolin at
10 mg/kg body weight and curcumin at 20 mg/kg body weight in
BALB/C Foxn nude mice for a 2-week period synergistically
inhibited CL-188 cell-derived tumor growth. Further analysis
showed that the synergistic anti-colon cancer effect exhibited
by curcumin and luteolin was mediated through the downregulation
of the effector protein Notch1, to induce growth cycle arrest,
promote apoptosis, and TGF-β signaling inhibits angiogenesis and
invasion in vitro and in vivo. These data demonstrate that a
combination of curcumin and luteolin exerts an anti-colon cancer
effect through the modulation of Notch1 and TGF-β signaling
pathways, well-known in cancer growth, invasion, and metastasis.
Antioxidant Potential of Phytoconstituents with Special
Emphasis on Curcumin Antimicrobial and
Pharmacological Aspects of Curcumin | June 2022 Curcumin, a
polyphenol, has been shown to target multiple signaling
molecules while also demonstrating activity at the cellular
level, which has helped to support its multiple health benefits
such as antioxidant, anti-inflammatory, antimutagenic,
antimicrobial and anticancer properties. Curcumin has received
worldwide attention for its multiple health benefits, which
appear to act primarily through its anti-oxidant and
anti-inflammatory mechanisms. Many major diseases such as liver
problem, myocardial infarction, diabetes, cancer are believed to
be associated with lipid peroxidation and thus causing major
cell damage. Curcuminoids and other polyphenols in turmeric can
ameliorate and prevent lipid peroxidation, can stabilize the
cell membrane, hence proving its significant role in prevention
of atherosclerosis. Inhibitory action of curcumin
on lipid accumulation, oxidation, nitric oxide as well as the
formation of inflammatory molecules, nuclear factor-kappa B-
(NF-kB-) dependent gene expression, and its activation can thus
influence therapeutic potential of turmeric in the treatment of
pancreatic, hepatic, cancer and intestinal diseases. Curcumin
can produce promisable symptomatic relief on external cancerous
lesions in human. Along with this, curcumin has resulted to be
effective in preventing and treatment of many of the
neurodegenerative disorders as a free radical scavenger
including Alzheimer’s disease. Also after giving short-term
supplementation it has proved to reduce hematuria, proteinuria,
including systolic blood pressure in patients with relapsed or
refractory lupus nephritis. By referring all the literature,
Curcumin can be considered as a safe adjuvant therapy. The
previous studies had indicated that the high antioxidant
properties of turmeric was found to inhibit cellular lipid
peroxidation and can also ameliorate other oxidative damage
caused by free radicals. Thus Turmeric is proven to be an
important source of high contents of flavonoids, polyphenols,
tannins and ascorbic acid. Curcumin as important
phytoconstituent of turmeric varieties is and effective and
important antioxidant compound and which can be effective in
management of various diseased conditions.
Efficacy of Curcumin on Treating Cancer
Anorexia-Cachexia Syndrome in Locally or Advanced Head and Neck
Cancer: A Double-Blind, Placebo-Controlled Randomised Phase IIa
Trial Journal of Nutrition and Metabolism |
June 2022 Curcuminoids are the extracts from curcumin, which
both in vitro and in vivo studies have shown the inhibitory
effect of NF-kB through intracellular phosphorylation. Siddiqui
et al. demonstrated that 100 mg/kg of curcumin prevented weight
loss in MAC16 colon tumour mice. Moreover, the increasing dose
of curcuminoid (up to 250 mg/kg) showed a 25% increase in body
weight in mice. Additionally, Gil da Costa et al. discovered
preventing myolysis in HPV-16-infected mice from curcuminoids by
the mechanism of downregulation of NF-kB synthesis resulted in
increased muscle mass or delayed muscle wasting compared with
controlled mice. For curcumin in clinical studies, Gupta et al.
showed that patients with solid cancer receiving chemotherapy
and curcumin for eight weeks showed a
significant improvement in their quality of life and a declined
NF-kB level compared with the controlled arm. Recently, our
previous study showed that 800 mg/day of curcumin delayed the
progression of handgrip muscle strength loss and basal metabolic
rate significantly among patients with solid cancer, as well as
there were no serious adverse events. Our study results showed
significantly improved skeletal muscle mass with the use of
curcumin compared with matching placebo, in which the difference
in the percent change in muscle mass between the groups was
significant. Moreover, body fat mass among patients treated with
curcumin showed a slower decline than patients treated with
matching placebo, even though no statistically significant
difference was noted between the two groups, but the trend seems
to favour curcumin. Our study showed that patients treated with
curcumin improved handgrip strength at week 8, but loss of
handgrip strength was observed in the matching placebo group.
Furthermore, in vivo studies demonstrated curcumin's crucial
significant immunomodulatory effect by stimulating PBMC
proliferation and cytokine production. Our study results
supported the related in vivo study that curcumin administration
for eight weeks resulted in less lymphocyte suppression compared
with the matching placebo group. The potential role of curcumin
regarding the immunomodulatory effect should be further
investigated among patients with cancer during treatment with
chemotherapy or immunosuppressive agents. For safety endpoint,
phase I studies suggested that curcumin at a dose up to 8,000 mg
once daily orally can be safely administered without
dose-limiting toxicity. Our study results demonstrated that
curcumin was well tolerated at a dose of 4,000 mg/day and showed
only mild grade of adverse events. No serious adverse events
were reported.
Review of the Effects and Mechanism of Curcumin in
the Treatment of Inflammatory Bowel Disease
Frontiers in Pharmacology | June 2022 Curcumin has been used
as a traditional herbal medicine in India and Southeast Asia for
thousands of years. It is often used to treat biliary tract
diseases, anorexia, rhinitis, cough, rheumatism, and various
chronic inflammatory diseases. Due to its extensive biological
activities, it has received widespread attention from
researchers in recent years. Current researching indicates that
curcumin has high medical value, including anti-inflammatory,
antioxidant, anti-tumor, anti-apoptotic, anti-fibrosis, immune
regulation and other effects, and can be used to treat a variety
of diseases (Salehi et al., 2019). It is involved in many
significant genetic and biochemical pathways (Karthikeyan et
al., 2020; Moniruzzaman and Min, 2020; Beyene et al., 2021).
Curcumin is associated with many cellular targets (i.e., NF-κB,
JAKs/STATs, MAPKs, TNF-γ, IL-6, PPARγ, and TRPV1) that
effectively reduce the progression of IBD. The research of
curcumin and related formulations for IBD treatment has surged
over the decade (Kahkhaie et al., 2019; Sharma et al., 2019;
Patel et al., 2020). So far, a large number of basic and
clinical studies have shown that curcumin has the effect of
treating IBD and also can maintain the remission of IBD (Yang H.
et al., 2017). In this review, the researches of IBD genetics
and pathogenesis and curcumin molecular targets in IBD in recent
years are summarized in order to provide reference for further
research and application of curcumin. Current researching
indicates that curcumin has high medical value, including
anti-inflammatory, antioxidant, anti-tumor, anti-apoptotic,
anti-fibrosis, immune regulation and other effects, and can be
used to treat a variety of diseases. A large number of basic and
clinical studies have shown that curcumin has the effect of
treating IBD and also can maintain the remission of IBD. In this
review, the research of curcumin on IBD in recent years is
summarized in order to provide reference for further research
and application of curcumin. At present, many researches have
proved that curcumin is safe and effective through DBPC test (Heger,
2017). Curcumin may not fit medical chemists’ definition of the
perfect drug, but many in vitro, in vivo and clinical trials
have irrefutably confirmed its medicinal potential (Li et al.,
2015; Beloqui et al., 2016; Yang et al., 2018; Yue et al., 2019;
Wei et al., 2021). We searched ClinicalTrials.gov to identify
current clinical trials evaluating curcumin treatment for IBD. A
total of 10 trials were included. Three of them have been
completed and five are in phase 3. Curcumin has less adverse
reactions and high safety during use. As a potential
chemotherapeutic drug, it shows a good application prospect in
both basic experimental researches and clinical trials of IBD
over the decades (Shapira et al., 2018; Sadeghi et al., 2020;
Sugimoto et al., 2020; Banerjee et al., 2021).
A
study on the effects of inhibition mechanism of curcumin,
quercetin, and resveratrol Journal of
Biomolecular Structure and Dynamics | June 2022 Curcumin is
the much better inhibitor than quercetin and resveratrol for hGR
according to both in vitro and in silico studies. Curcumin, a
potential inhibitor of hGR, can be used in drug design to target
the glutathione system in cellular injury.
Curcumin as adjuvant treatment in patients with
non-alcoholic fatty liver (NAFLD) disease: A systematic review
and meta-analysis Complementary Therapies
in Medicine | June 2022 Turmeric (Curcuma longa) has active
constituents in its rhizome called curcuminoids, with the most
prominent curcuminoid called curcumin. Curcumin is acknowledged
as a powerful antioxidant and anti-inflammatory agent. Curcumin
is given through an oral capsule and taken daily. Two
trials’ participants received 500 mg curcumin and 5 mg
piperine/day as intervention. A review reported that the
consumption of curcumin significantly reduced liver enzymes,
decreased low-density lipoprotein and total cholesterol among
non-alcoholic fatty liver disease (NAFLD) patients. Another
review found curcumin showed significant effects on fasting
blood sugar, insulin level, and homeostasis model of assessment
insulin resistance8 among women with polycystic ovary syndrome.
Curcumin is anticipated to function as antiviral drugs to treat
the current COVID-19 virus based on in vitro and in vivo studies
as it showed high inhibitory activity towards the virus.
Computer simulation and molecular docking showed the good
ability of this monomer to bind to the COVID virus and host
target so that they could block the virus-host binding sites.
Curcumin has been shown to improve non-alcoholic fatty liver
disease (NAFLD) severity and increase liver steatosis resolution
compared to the placebo groups. Besides improving the liver
ultrasonographic findings, curcumin also reduced serum liver
enzymes, total cholesterol, and BMI. There is no major side
effect, and our findings showed no difference in the adverse
effect between the two groups. Curcumin was also found to reduce
triglycerides if taken more than eight weeks’ duration.
Our meta-analysis shows that curcumin has favorable effect on
liver ultrasonographic findings, reduced serum liver enzymes,
total cholesterol, and BMI in participants with non-alcoholic
fatty liver disease (NAFLD). Therefore, promoting curcumin as an
adjuvant treatment on non-alcoholic fatty liver disease (NAFLD)
patients might be justified.
Profiling of curcumin-treated T47D
human breast cancer cells by a system-based approach
Gene Reports | June 2022 This study investigated the
regulatory mechanism of curcumin in breast cancer cells.
Curcumin triggers cell death-related pathways and regulates the
metabolism of lipids and apoptotic processes in T47D cells.
Curcumin signature had significant prognostic power. Regulatory
network analyses found specific proteins, microRNAs and
transcription factors as the hub nodes, which corresponded to
the effects of curcumin treatment. This work provides a picture
of the cytotoxicity mechanism of curcumin and potential
therapeutic targets for treatment optimization of breast cancer.
The efficacy of curcumin-piperine co-supplementation
on clinical symptoms, duration, severity, and inflammatory
factors in COVID-19 outpatients: a randomized double-blind,
placebo-controlled trial Trials | June 2022
Curcumin as an anti-inflammatory agent can have a positive
effect on the control of COVID-19 complications. This study
aimed to assess the efficacy of curcumin-piperine
supplementation on clinical symptoms, duration, severity, and
inflammatory factors in patients with COVID-19. Forty-six
outpatients with COVID-19 disease were randomly allocated to
receive two capsules of curcumin-piperine; each capsule
contained 500 mg curcumin plus 5 mg piperine or placebo for 14
days. The present study results showed that curcumin-piperine
co-supplementation in outpatients with COVID-19 could
significantly reduce weakness.
Curcumin
attenuates vascular calcification via the exosomal
miR-92b-3p/KLF4 axis Experimental Biology
and Medicine | June 2022 Curcumin is a natural polyphenolic
compound that has hypolipidemic, anti-inflammatory, and
antioxidant effects on the cardiovascular system. Exosomes are
known to have extensive miRNAs for intercellular regulation. Our
study suggests that curcumin attenuates vascular
calcification.
Role of Curcumin in the Management of Schizophrenia: A Narrative
Review Indian Journal of Psychological
Medicine | June 2022 Curcumin is a polyphenolic molecule
derived from Curcuma longa. In traditional medicine,
turmeric is commonly used as an anti-inflammatory and antiseptic
agent. Its antioxidant property and low toxicity potential are
utilized in physical disorders like rheumatioid arthritis,
cardiovascular disorders, asthma, and neuropsychiatric disorders
like Alzheimer’s dementia and Parkinsonism. There are no
available reports of toxicity in humans following long-standing
use of curcumin. An exploratory proof-of-concept study examined
the effects of curcumin combined with piperine (from black
pepper extract–used to improve the bioavailability of curcumin)
as an add-on to the ongoing antipsychotic treatment. Fifteen
chronic schizophrenia patients were randomized to receive 1 g vs
4 g of add-on curcumin and piperine compounds. At the end of 16
weeks, both groups showed significant improvements in total
scores and general psychopathology subscale of the Positive and
Negative Syndrome Scale (PANSS). Both the doses were tolerated
well without much adverse effects. The role of curcumin in the
management of depression and bipolar disorder has been proposed
recently. Curcumin as an add-on to antidepressant drugs has been
convincingly shown to reduce depressive symptoms, compared to
placebo add-on. A recent meta-analysis supported the utility of
adjunctive curcumin in the management of depression and anxiety
disorders. Notably, curcumin was tolerable and safe in all those
randomized human clinical trials. Preclinical studies
support curcumin’s role in ameliorating the metabolic side
effects of antipsychotics such as olanzapine 28 and clozapine.
Also, pretreatment with curcumin prevented the development of
tardive extrapyramidal syndromes. In both haloperidol and
clozapine exposed rats, pretreatment with curcumin successfully
prevented the development to tardive orofacial movements.
Curcumin’s antioxidant, free radical scavenging, and
antiapoptotic properties are postulated to underlie this
preventive mechanism. Preclinical studies also reported
curcumin’s beneficial effects in preventing and reducing
extrapyramidal and metabolic side effects. Preclinical and
clinical trials reported curcumin’s potential role in the
management of schizophrenia.
Comparative
Study of the Anticoagulant Activity of Zingiber Officinale and
Curcuma longa Rhizomes Extracts in Blood Samples of Normal
Individuals Pakistan Journal of Medical &
Health Sciences | June 2022 The in vitro anticoagulant effect
demonstrated that ginger and curcumin extracts had equal
anticoagulant activity, but curcumin has a higher anticoagulant
impact with considerable PT prolongation.
Curcumin and Related Compounds in Cancer Cells: New
Avenues for Old Molecules Frontiers in
Pharmacology | June 2022 Curcumin and related compounds are
bioactive compounds mainly derived from natural sources and
known for years for their pleiotropic effects. These compounds
show anti-viral, anti-fungal, anti-microbial and anti-tumor
effects (Chiao et al., 1995; Beauregard et al., 2015; Balaha et
al., 2021), mainly ascribable to anti-inflammatory and
antioxidant activities. Curcumin and derivatives have been
proposed as potential therapeutic agents in selected cancer
types such as prostate, colon, breast and thyroid cancer (Schwertheim
et al., 2017; Mbese et al., 2019) and their anticancer effects
have been tested in vitro and in vivo in combination with
chemotherapeutic agents and radiotherapy (Yu et al., 2021).
Curcumin has shown to amplify the anticancer effects of drugs
(e.g., doxorubicin, cisplatin, gefitinib) and radiotherapy (Tan
and Norhaizan, 2019; Ashrafizadeh et al., 2020). For instance,
curcumin displays a synergistic effect with some
chemotherapeutic agents such as 5-fluorouracil and oxaliplatin (Farhood
et al., 2019) while protecting normal tissues from cell death,
and therefore without side effects.
Effect of Interval Training and Curcumin on BAX,
Bcl-2, and Caspase-3 Enzyme Activity in Rats
Gene, Cell and Tissue | June 2022 Curcumin is a
polyphenol used as a painkiller, anti-inflammatory agent, and a
source of powerful antioxidants. Numerous studies have confirmed
the biological effects of curcumin and introduced it into
various pathological conditions. It contains many anti-diabetic,
anti-tumor, anti-inflammatory, and antioxidant agents. Curcumin
activates the caspase-3 enzyme and releases cytochrome c from
the mitochondria to the cytosol. Also, curcumin can improve
athletic performance and delay exercise fatigue. Studies have
shown that curcumin synergizes with 5-fluorouracil and enhances
apoptosis in cancer cells in xenograft mice. If curcumin enters
cancer cells, it activates programmed cell death pathways.
High-intensity interval training did not reduce BAX protein, but
the training and curcumin supplementation increased Bcl-2
protein expression and neutralized the BAX effect. Curcumin
supplementation combined with intense interval training resulted
in synergy and reduced cell programming mortality. Therefore,
curcumin supplementation and intermittent exercise can reduce
cell apoptosis and programmed cell death.
Curcumin Blocks High Glucose-Induced Podocyte Injury
via RIPK3-Dependent Pathway Frontiers in
Cell and Developmental Biology | June 2022 Curcumin, a
natural hydrophobic polyphenol compound responsible for the
yellow color in Curcuma longa, has gathered attention
from various research fields due to its natural antioxidant,
anticancer, anti-inflammatory, antiangiogenic, and antiapoptotic
effects (Gururaj et al., 2002; Majithiya and Balaraman, 2005;
Koeberle et al., 2009; Perrone et al., 2015; Zhang et al.,
2020). The effect of curcumin on high glucose-induced podocyte
injury has been discussed in few studies, mainly focusing on
curcumin’s antioxidant and anti-inflammatory properties (Kanitkar
et al., 2008; Meng et al., 2013; Den Hartogh et al., 2019).
Curcumin has recently been reported to have a protective effect
on hepatocyte or neuronal cells prone to necroptosis (Dai et
al., 2013; Lu et al., 2016). Our study showed that curcumin had
protective effects against oxidative stress, inflammatory
response, and fibrosis in high glucose-induced podocyte injury,
eventually improving podocyte function. These renoprotective
effects of curcumin might be associated with its ability to
inhibit high glucose-induced RIPK3 expression by inhibiting
oxidative stress. Our observations suggest that curcumin might
be a potential therapeutic agent to minimize the progression of
podocytopathy caused by diabetes as an inhibitor of RIPK3.
Results indicate that curcumin treatment can protect against
high glucose-induced podocyte injuries by suppressing the
abnormal expression of ROS and RIPK3. Thus, curcumin might be a
potential therapeutic agent for diabetic nephropathy as an
inhibitor of RIPK3.
Curcumin activates NLRC4, AIM2, and IFI16
inflammasomes and induces pyroptosis by up-regulated ISG3
transcript factor in acute myeloid leukemia cell lines
Cancer Biology & Therapy | June 2022 Curcumin, an active
ingredient derived from turmeric, has been recognized for its
medicinal properties, including antioxidant, anti‐inflammation,
radical‐scavenging, anti-solid and -blood tumor, and so on. The
anticancer effects of curcumin mainly result from multiple
biochemical mechanisms that are involved in the regulation of
programmed cell death, such as apoptosis, autophagy. Recent
studies have found that curcumin can induce pyroptosis of solid
tumor cells. Prior studies have shown that curcumin exert
anti-cancer effects by induction of apoptosis and autophagy. We
have discovered that curcumin can induce leukemia cell death by
increasing apoptosis and pyroptosis and that activated AIM2,
IFI16, and NLRC4 inflammasomes play a key role in this process.
In addition, the anti-leukemia effect of curcumin is affected by
the expression of GSDMD. Thus, pyroptosis may be a potential new
strategy for treating leukemia, and GSDMD is a biomarker to
evaluate curcumin sensitivity in the leukemia therapy.
Effect
of Curcumin on Apoptosis of Acute T-Lymphoblastic Leukemia Cells
CNKI | June 2022 Curcumin can enhance the apoptosis of T-cell
acute lymphoblastic leukemia (T-ALL) cells induced by Mcl-1
small molecule inhibitor UMI-77 by reducing the mitochondrial
membrane potential, the mechanism may be related to the
inhibition of Notch1 signaling pathway.
Curcumin inhibits the cancer‑associated
fibroblast‑derived chemoresistance of gastric cancer
International Journal of Oncology | June 2022 Curcumin
abrogated the CAF‑mediated activation of the JAK/STAT3 signaling
pathway in GC cells. In vivo data revealed the synergistic
effects of curcumin with 5‑FU treatment in xenograft GC tumors.
These data strongly suggest that the suppression of the
JAK/STAT3 signaling pathway counteracts the CAF‑induced
chemoresistance of GC cells. It is suggested that curcumin may
be a suitable natural product which may be used to overcome
chemoresistance by inhibiting the CAF‑induced activation of the
JAK/STAT3 signaling pathway in GC.
The effect of curcumin supplementation on
delayed-onset muscle soreness, inflammation, muscle strength,
and joint flexibility: A systematic review
Phytotherapy Research | May 2022 Curcumin supplementation
significantly reduced serum creatine kinase activity, muscle
soreness, and TNF-α concentration. Also, curcumin
supplementation elicited significant improvements in maximal
voluntary contraction (MVC) and range of motion (ROM). Curcumin
supplementation may improve some aspects of delayed-onset muscle
soreness (DOMS), including muscle damage, muscle soreness,
inflammation, muscle strength, and joint flexibility.
Antiproliferative
Effects of Curcumin Different Types of Breast Cancer
Journal of Cancer Prevention | May 2022 Breast cancer is one
of the most frequently diagnosed malignancy among women.
Turmeric is isolated from Curcuma longa. Curcumin is main
curcuminoid of the turmeric which is a member of Zingiberaceae.
In this current study antiproliferative effects of curcumin were
investigated in luminal A breast cancer cell line MCF-7 and
triple negative breast cancer cell line MDA-MB-231. Curcumin,
which has antiproliferative effects on breast cancer cells, is
thought to be effective in cancer treatment.
Effect
of Curcumin on Hippocampal Neurons, Learning, and Spatial Memory
in a Model of Global Cerebral Ischemia Red
Crescent Medical Journal | May 2022 Curcumin administration
reduced spatial memory impairment in the treatment group
compared to the ischemia group. These results suggest that
pretreatment with curcumin can improve memory and learning
disorders and hippocampal neuron damage following ischemia.
Role of curcumin in ameliorating hypertension and
associated conditions: a mechanistic insight
Molecular and Cellular Biochemistry | May 2022 Since ancient
times, curcumin has been in use as food spices and folk remedy
to treat cough, cold, cuts and wounds, and skin diseases.
Preclinical and clinical studies have indicated that curcumin
acts a promising therapeutic agent in the management of a wide
array of health issues, viz., hyperlipidemia, metabolic
syndrome, anxiety, arthritis, cancer and inflammatory diseases.
Owing to its enormous potential, recent research has been
focused on the synthesis of curcumin and its analogues for the
management of metabolic disorders. In the current scenario,
hypertension is considered as a key risk factor due to its
involvement in various pathogeneses. Mechanistically, curcumin
and its analogues have been reported to elicit anti-hypertensive
effect through diverse signalling pathways.
The
effects of curcumin as dietary supplement for patients with
COVID-19: A systematic review of randomized clinical trials.
Drug Discoveries & Therapeutics | May 2022
Accumulating evidence has been reported regarding the effect of
curcumin as a dietary antiviral on patients with COVID-19. Our
review revealed that curcumin might have a positive effect on
relieving COVID-19 related inflammatory response due to its
powerful immune-modulatory effects on cytokines production,
T-cell responses, and gene expression. These findings suggest
that curcumin confers clinical benefits in patients with
COVID-19.
Molecular
Mechanism of Curcumin and Its Analogs as Multifunctional
Compounds against Pancreatic Cancer
Nutrition and Cancer | May 2022 Curcumin is a natural
chemical substance obtained from plants with a wide range of
pharmacological activities. Research evidence suggests that
curcumin can influence PC development through multiple molecular
mechanisms. This review aims to summarize the mechanisms
of action of curcumin in preclinical and clinical studies on PC
and research progress in enhancing its bioavailability.
An
Overview of Parkinson's Disease: Curcumin as a Possible
Alternative Treatment Cureus | May 2022
Curcumin, turmeric's active ingredient, has antioxidant,
anti-apoptotic, and anti-inflammatory properties that protect
tissues from the harmful effects of reactive oxygen species
(ROS). Curcumin's protective properties start with its
ability to cross the blood-brain barrier due to its lipophilic
nature. Curcumin has various protective properties in the brain,
including protection against toxic metals and ROS. Toxic metal
ions can interfere improperly with tissues in the brain, causing
neurological damage. Curcumin, as a flavonoid, has antioxidant
properties that are potentially stronger than typical
antioxidants such as vitamins C and E.
Curcumin also protects against A53T α-synuclein
aggregation and monoamine oxidase B, becoming a compound of
interest in treating neurodegenerative disorders such as
Parkinson's disease. Curcumin has been found to protect
nigrostriatal dopaminergic neurons from damage in animal models.
Curcumin had protective effects on alpha7-nicotinic
acetylcholine receptors after administration of
6-hydroxydopamine (6-OHDA) in rats with a curcumin dose of 200
mg/kg. Curcumin restored nigrostriatal dopamine neurons to 87.3%
and 84.8%. Curcumin's ability to donate an H ion from the
beta-diketone moiety is thought to be responsible for its
anti-ROS properties. Curcumin protects mitochondria and neurons
from the damaging effects of ROS by donating an H ion.
Curcumin's powerful antioxidant capabilities, including
chelation of harmful metals and lowering ROS, may help reduce
inflammation and apoptosis. Because neurons are terminal
tissues, reducing ROS may improve their longevity and the
efficacy of pharmaceutical therapies. These findings imply that
curcumin could be used in conjunction with standard Parkinson's
disease medication to improve treatment and results.
Antitumor Properties of Curcumin in Breast Cancer Based on
Preclinical Studies: A Systematic Review
Cancers | May 2022 Studies have shown that curcumin
administered at different concentrations inhibited
proliferation, decreased viability, and induced apoptosis in
human and animal breast cancer cells. This review assesses
the antitumor effects of curcumin on breast cancer reported in
preclinical in vitro and in vivo animal models. We used five
databases to search for preclinical studies published up to May
2021. The assessments included the effects of curcumin on the
proliferation, viability, and apoptosis of breast cancer cell
lineages and on tumor volume. In total, 60 articles met the
inclusion criteria. Curcumin administered at different
concentrations and via different routes of administration
inhibited proliferation, decreased viability, and induced
apoptosis in human and animal breast cancer cells.
Docking
Analysis of Some Bioactive Compounds from Traditional Plants
against SARS-CoV-2 Molecules | May 2022
Curcumin and its analogues are the main phytonutrients of
turmeric (Curcuma longa L.) which is widely used
around the world as culinary spices, traditional medicine as
well as a popular dietary supplement ingredient due to its wide
range of health benefits including anti-inflammation,
anti-cancer, cardiovascular regulation, respiratory, and immune
system benefits. In addition, the suppression of multiple
cytokines by curcumin suggested that it may be a useful approach
in treating curcumin, and demothoxycurcumin exhibited high
binding affinity on SARS-CoV-2 S- protein, PLpro, and RdRp.
Binding of these proteins interfere with the viral entry,
replication, and immune response evasion. Therefore, these
compounds may have a great potential for inhibiting the virus.
Curcumin
and Thymoquinone Combination Attenuates Breast Cancer Cell
Lines’ Progression Integrative Cancer
Therapies | May 2022 Curcumin, the active ingredient of
Curcuma longa, is the most studied compound described as a
potential anticancer agent. Curcumin targets multiple
signaling/molecular pathways including, Rb, p53,
mitogen-activated protein kinase, phosphatidylinositol 3-kinase
(PI3K)/protein kinase B (AKT), and nuclear factor kappa B cells
(NF-κB). Previous studies have demonstrated that curcumin can
inhibit cancer cell proliferation. Recently, curcumin was
reported to suppress breast cancer cell proliferation and
migration through autophagy-dependent AKT degradation and
increased natural killer cells activity. Curcumin, TQ, and their
combination induced significant apoptosis of both cells and
hindered their progression. Several reports have shown the
anticancer effect of either curcumin or TQ against MCF7
and MDA-MB-231 cell lines. One interesting finding is
curcumin , TQ, and their combination had synergistic effects.
Curcumin decreased proliferation and colony formation
activities in MCF7 and MDA-MB-231 cell lines. This study
supports evidence from previous observations of
Effenberger-Neidnicht and Schobert,31 Attoub et al,32 Masuelli
et al,33 Zhou et al,34 and El-Far et al16 who reported
significant increases in caspase-3 expression, protein levels,
or activities in either MCF7 or MDA-MB-231 cell lines treated
with curcumin. These results suggest the promising anticancer
benefit of the curcumin and TQ combination against breast
cancer.
Curcumin Inhibits the Growth and Metastasis of
Melanoma via miR-222-3p/SOX10/Notch Axis
Disease Markers | May 2022 Due to its antiinflammatory and
antioxidant properties, curcumin has been also reported to have
significant health benefits, including improved brain function
and anticancer/anti-therosclerotic properties. A previous study
has been indicated that curcumin could inhibit breast cancer
cells proliferation and invasion via repressing the NF-κB
inducing genes. It has been suggested that curcumin could
influence the G0/G1 phase arrest by MTA1- (metastasis-associated
protein 1-) induced inactivation of Wnt/β-catenin pathway in the
lung cancer cell. In gastric cancer, curcumin could induce MMP
proteins dissipation and cytochrome C into the cytosol in
SGC-7901 cell lines, resulting in the downregulation of
migration ability and apoptosis escaping. In colon cancer HCT116
and HT29 cells, curcumin could inhibit the level and activity of
hexokinase II (HKII) by a concentration-dependent manner,
inducing cell apoptosis. There is also an increasing number of
studies showing that curcumin can also induce apoptosis and
inhibit proliferation of melanoma cancer cells. In summary,
these results indicated that curcumin was a key role in impeding
the proliferation, migration, and invasion ability of melanoma
cells. Curcumin could inhibit the proliferation, migration, and
invasion of melanoma cells. Furthermore, curcumin repress the
expression of SOX10, Notch1, and HES-1, and increase the
expression of miR-222-3p. In addition, inhibition of miR-222-3p
expression reversed the inhibitory effect of curcumin the growth
of melanoma cells. Curcumin enhances the miR-222-3p level to
reduce SOX10 expression, and ultimately inactivates the Notch
pathway in repressing melanoma proliferation, migration, and
invasion. According to the above, curcumin represents a
potential therapeutic agent for the treatment of melanoma.
Curcumin inhibits spike protein of new SARS-CoV-2
variant of concern (VOC) Omicron Computers
in Biology and Medicine | May 2022 Curcumin, among seven
phytochemicals, was found to have the most substantial
inhibitory potential with Omicron S protein. Further, it was
found that curcumin could disrupt the Omicron S-hACE2 complex.
The molecular dynamic simulation demonstrated that Curcumin
could form a stable structure with Omicron S in the
physiological environment. Conclusion To conclude, Curcumin can
be considered as a potential therapeutic agent against the
highly infectious Omicron variant of SARS-CoV-2.
Curcumin
supplementation may improve metabolic, inflammatory, and obesity
markers in women with rheumatoid arthritis.
Clinical Edge Journal Scan | May 2022 Curcumin consumption
for 8 weeks as a part of an integrated approach could help
modulate metabolic factors, inflammation, and adiposity in women
with rheumatoid arthritis. Major finding: After 8 weeks, insulin
resistance, erythrocyte sedimentation rate, serum levels of
high-sensitivity C-reactive protein, and triglycerides improved
significantly in the curcumin supplementation vs. placebo group.
Moreover, curcumin supplementation significantly decreased mean
weight, body mass index, and waist circumference vs. no
significant changes observed in placebo group.
Curcumin can improve Parkinson's disease via
activating BDNF/PI3k/Akt signaling pathways
Food and Chemical Toxicology | May 2022 Curcumin, as one of
the natural polyphenols, is significant in stimulating
PI3k/Akt/glycogen synthase kinase 3 (GSK3) and BDNF/tyrosine
kinase receptor B (TrkB)/PI3k/Akt signaling pathways, has great
potential in neurodegenerative diseases and other different
pathological settings. Curcumin can delay the progression of
Parkinson's disease by protecting nerve cells.
The
potential of curcumin for treating spinal cord injury: a
meta-analysis study Nutritional
Neuroscience | May 2022 Curcumin had a strong significance in
improving functional recovery after spinal cord injury. When
curcumin was administered daily, it had a stronger effect than
single-dose treatment or weekly administration. Curcumin also
significantly reduced the expression of GFAP (Glial fibrillary
acidic protein) marker compared to untreated groups. These
findings suggest that daily administration of curcumin can be an
effective approach to improving functional recovery after spinal
cord injury.
Therapeutic
role of curcumin in adult neurogenesis for management of
psychiatric and neurological disorders: a scientometric study to
an in-depth review Critical Reviews in Food
Science and Nutrition | May 2022 Curcumin is a primary
constituent of curcuminoid that exerts several positive
pharmacological effects on aberrant neurogenesis. We explore the
mechanisms by which curcumin regulates adult neurogenesis and in
turn affects psychiatric diseases, i.e., depression and
neurological disorders among them traumatic brain injury (TBI),
stroke, Alzheimer’s disease (AD), Gulf War Illness (GWI) and
Fragile X syndrome (FXS). This review aims to elucidate the
therapeutic effects and mechanisms of curcumin on adult
neurogenesis in various psychiatric and neurological disorders.
Specifically, we discuss the regulatory role of curcumin in
different activities of neural stem cells (NSCs), including
proliferation, differentiation, and migration of NSCs. This is
geared toward providing novel application prospects of curcumin
in treating psychiatric and neurological disorders by regulating
adult neurogenesis.
The Impact of Curcumin on the Inflammatory Profile
of SW982 Cells in a Rheumatoid Arthritis Model
Journal of Immunology Research | May 2022 Curcumin, a natural
polyphenol extracted from Curcuma longa, possesses plenty of
proven properties, beneficial in ameliorating autoimmunological
diseases, such as rheumatoid arthritis. Due to its structure,
curcumin is a free radical scavenger, reducing redox-related
inflammatory signaling. Profitable attributes of curcumin have
been shown to lay a heavy impact on the functionality of
rheumatoid arthritis by reducing their survivability and hence
the number of overproliferating cells, decreasing expression of
IL-1β, TNF-α, and COX-2 proteins and diminishing production of
tissue destroying metalloproteinases. Presented
anti-inflammatory properties, safety, and low cost of usage make
curcumin a great candidate for potential therapies, which are
already tested in trials conducted on patients with Rheumatoid
arthritis. Aside from proving the overall anti-inflammatory
properties of curcumin, results of conducted experiments showed
some of the molecular basics of its action. Conducted
investigations indicate the promising role of curcumin in
decreasing the inflammation, enhancing its position as the
potential compound in potential rreumatoid arthritis therapies.
Therapeutic
Effects of Curcumin on Osteoarthritis and Its Protection of
Chondrocytes Alternative Therapies in
Health and Medicine | May 2022 The curcumin group show
higher improvements in safety, joint mobility, and inhibition of
inflammation. In-vitro experiments showed that curcumin
inhibited the apoptosis rate of chondrocytes and the levels of
inflammatory factors, while the Wnt/β-catenin inhibitor did the
opposite. Curcumin can effectively decrease the pathological
results of OA, with a remarkable safety profile; its mechanism
may be the activation of the Wnt/β-catenin signaling pathway to
inhibit the inflammatory reaction and apoptosis in chondrocytes.
Curcumin treats endometriosis in mice by the HIF
signaling pathway American Journal of
Translational Research | May 2022 Curcumin has become a hot
topic in medical research because of its various pharmacological
activities, such as anti-inflammatory and antioxidant. Curcumin
has therapeutic effects on a variety of human diseases,
including cancer, cardiovascular disease, diabetes, arthritis,
neurologic disorders, Crohn’s disease, and cardiovascular
disease. The modulation of curcumin for tumors has received the
most attention from researchers; approximately 37% of curcumin
studies are related to tumors. Curcumin can modulate multiple
cellular signaling pathways simultaneously to alleviate or
prevent different types of cancer, including multiple myeloma,
colorectal, pancreatic, breast, prostate, and lung cancers,
because it can modulate growth factors, enzymes, transcription
factors, kinases, inflammatory cytokines, and apoptotic
proteins. Previous studies focused on the antioxidant stress
capacity of curcumin, which reduced ROS directly by enhancing
the intracellular levels of reduced glutathione and counteracted
antioxidants by increasing the activity of antioxidant enzymes
and activating the Nrf2-Keap1 pathway. Our study demonstrated
for the first time that curcumin can treat endometriosis and
improve disease hypoxia through the HIF-1α pathway. Consistent
with previous studies, curcumin exhibited therapeutic effect on
endometriosis by inhibiting oxidative stress, thus alleviating
inflammation. The real situation may be that curcumin inhibits
oxidative stress on the one hand and improves hypoxia on the
other hand. The number of lesions, volume, and degree of
adhesions were significantly reduced in the curcumin group
compared to the negative control group and the control group.
Curcumin played a role in the treatment of endometriosis by
modulating the HIF signaling pathway, improving the local
hypoxia of the lesion, and reducing the inflammatory state of
endometriosis.
Curcumin: A therapeutic strategy for targeting the
Helicobacter pylori-related diseases
Microbial Pathogenesis | May 2022 Curcumin exhibits
anti-inflammatory, anti-carcinogenic, anti-oxidant properties
and is widely used as a natural product-derived medicine or
nutraceutical. Furthermore, curcumin has been reported to have
anti-bacterial activity. Therefore, curcumin might be an
effective herbal-based medicine for preventing, managing, or
treating H. pylori infection. This review discusses the
anti-inflammatory, anti-cancer, and anti-bacterial properties of
curcumin as it pertains to gastric cancer and H.
pylori-associated diseases.
Curcumin Selectively Induces Colon Cancer Cell
Apoptosis and S Cell Cycle Arrest by Regulates Rb/E2F/p53
Pathway Journal of Molecular Structure |
May 2022 Curcumin has anti-inflammatory and anti-tumor
activity. Curcumin induces cells apoptosis through
p53-mediated mechanism. Curcumin destabilizes cell cycle
distributions by Rb/CDK/E2F signaling pathway. Curcumin inhibits
tumor growth in vivo. Our data showed that curcumin
preferentially and, in a dose, dependent way inhibited colon
cancer cells proliferation, but was not toxic to normal colon
mucosa epithelial cells. Curcumin induced apoptosis through a
p53-mediated mechanism. Curcumin may be a potential strategy for
the treatment of colon cancer.
The
effect of curcumin on the risk of mortality in patients with
COVID-19: A systematic review and meta-analysis of randomized
trials Phytotherapy Research | April 2022
Curcumin is a natural polyphenolic compound with multiple
benefits, including antiviral, anti-inflammatory, anticoagulant,
antiplatelet, and cytoprotective, which have been demonstrated
to be advantageous in reducing the progression of several
inflammatory illnesses (Rattis, Ramos, & Celes, 2021). The
aforementioned effects have made curcumin one of the potential
treatment options for patients with COVID-19. Since the
pathophysiology of COVID-19 is known to involve life-threatening
inflammatory reactions, cytokine storms, and coagulopathy,
curcumin can be advantageous due to its anti-inflammatory
effects via the inhibition of inflammasome formation (Yin et
al., 2018). In addition, curcumin also demonstrates antiviral
effects via its ability to bind to the viral primary protease
(Mpro) enzyme of SARS-CoV-2, which is required for viral
replication. Curcumin also prevents viral attachment and passage
into the host cell with great potency (Dourado et al., 2021).
The ability of curcumin in inhibiting the virus-receptor
interaction is in two ways, according to modeling studies: it
inhibits both the spike protein and the ACE2 receptor (Manoharan
et al., 2020). Previously in this journal, the findings of the
randomized trial reported by Hassaniazad et al. (2021) suggest
that curcumin can accelerate the recovery of acute inflammatory
phase in patients with COVID-19 by modulating inflammatory
immune responses.
Curcumin as a Potential Therapeutic Agent in Certain
Cancer Types Cureus | April 2022
Curcumin has no noticeable toxicity and, in combination with
existing chemotherapeutic agents, is a superior treatment option
for certain cancer types. The potential applications of curcumin
include the prevention and treatment of cancer,
anti-inflammatory/antioxidant, and antiangiogenic activities.
These beneficial effects of curcumin are exerted by modulating
signaling molecules, including cytokines, chemokines,
transcription factors, adhesion molecules, microRNAs, tumor
suppressor genes, etc.. Several studies have shown the antitumor
activity of curcumin on breast cancer, prostate cancer, brain
cancer, lung cancer, and pancreatic cancer. Curcumin is a potent
anti-oxidative, anti-inflammatory, and anti-tumor agent, and it
is extracted from rhizomes of Curcuma species.
Curcumin, as a cancer treatment agent, is recognized to affect
multiple targets in different stages of cancer, including
angiogenesis, proliferation, metastasis, and apoptosis. The
molecular mechanism of action of curcumin has been studied
comprehensively. It exerts this effect by interfering with
several cell-signaling pathways as well as inducing and
inhibiting the production of various growth factors, enzymes, or
cytokines. Its therapeutic effects for the breast, lung,
prostate, intestinal, liver, and hematological malignancies have
been proven in the pre-clinical as well as in vivo studies.
Effects of Curcumin on Inflammatory Response During
Exercise-Induced Muscle Damage Biointerface
Research in Applied Chemistry | April 2022 The results of this
study explain that curcumin was able to provide anti-
inflammatory effects by reducing pro-inflammatory cytokines such
as IL-6, IL-8, TNF-α. Curcumin can also reduce muscle pain
intensity, decrease CK activity, and increase ROM. The curcumin
dose showed to reduce various inflammatory responses due to
EIMD. Therefore, it is recommended that curcumin be used in
individuals who carry out physical activities, leading to muscle
damage and inflammation. Curcumin's anti-inflammatory benefits
have been well known. Curcumin works by altering COX-2 pathway
signaling, resulting in decreased pro-inflammatory cytokine and
prostaglandin production. Curcumin is able to provide
anti-inflammatory effects by reducing pro-inflammatory cytokines
such as IL-6, IL-8, TNF-a. Curcumin can also reduce muscle pain
intensity, decrease CK activity, and increase ROM. We recommend
that curcumin be used in individuals who engage in physical
activity that results in muscle damage and inflammation.
Specific Metabolic Response of Patient-derived
Organoids to Curcumin of Colorectal Cancer
Journal of Chromatography | April 2022 Curcumin has been found
to be effective in suppressing various phases of colorectal
cancer development. Our research provided a reference for
further revealing the role of curcumin in human-derived
colorectal cancer-like solid tumors.
Quality of Evidence Supporting the Role of Curcuma
Longa Extract/Curcumin for the Treatment of Osteoarthritis: An
Overview of Systematic Reviews
Evidence-Based Complementary and Alternative Medicine | April 2022
Recently, curcuma longa extract, an anti-inflammatory and
antioxidant preparation) has been used in traditional Chinese
medicine and Ayurveda to treat arthritis and has thus become an
attractive treatment option for improving the joint condition of
OA patients. Often used as an alternative medicine or dietary
supplement, turmeric is typically an extract that is
standardized to 80–95% curcuminoids, among which curcumin is the
most active ingredient in turmeric and is “generally regarded as
safe” by the US FDA. In addition, the curcumin alone has
anti-inflammatory properties similar to NSAIDs. Well known for
its good anti-inflammatory effect, curcuma longa extract has a
potential effect on osteoarthritis, and a large number of
researchers have completed several systematic
reviews/meta-analyses in this research area. According to the
available published evidence, curcumin may be effective and safe
for the treatment of osteoarthritis.
Curcumin for attention-deficit–hyperactivity
disorder (ADHD) a systematic review and preliminary behavioral
investigation Naunyn-Schmiedeberg's
Archives of Pharmacology | April 2022 Curcumin has protective
actions in neuropsychiatric disorders, acting as a
neuroprotective agent. As a first approach, the study aimed at a
systematic review of the potential effects of curcumin on
cognitive performance for attention-deficit–hyperactivity
disorder (ADHD). The results of the Y-Maze Test demonstrated
that curcumin improved spatial memory.
Protective Effects of Curcumin-Regulated Intestinal
Epithelial Autophagy on Inflammatory Bowel Disease in Mice
Gastroenterology Research and Practice | April 2022 This study
was aimed at exploring the ameliorating effect of curcumin on
inflammatory bowel disease (IBD) in mice induced by 3% dextran
sodium sulfate (DSS) by regulating intestinal epithelial cell
autophagy. Compared with that of the DSS group, the diet of mice
in the curcumin group was improved, the decline of body weight
was slowed down, the hair glossiness was restored, the blood in
the stool gradually decreased or occulted, the DAI score was
decreased, the colon tissue was significantly improved, the
expressions of LC3-II/LC3-I and Beclin1 were significantly
increased, and the p62 was significantly decreased. Therefore,
curcumin can increase the expression level of autophagy protein in
IBD mice, which may be one of the molecular mechanisms for the
treatment of IBD intestinal inflammation.
Anticancer Properties of Curcumin Against Colorectal
Cancer: A Review Frontiers in Oncology |
April 2022 Several studies show that curcumin belongs to a
class of plant-derived chemicals that can help prevent
colorectal cancer. Several possible pathways have been proven in
both in vitro and in vivo animal studies. Furthermore, treatment
improvements in animals with inflammatory and hereditary
colorectal cancer have been discovered. The Curcuma longa roots
(dried) plant are used to produce curcumin. It has been
discovered to have anti-carcinogenic properties. Curcumin has
the ability to target colon cancer cells specifically, while
allowing normal cells to remain alone; cancerous cells die as a
result of an elevation in the expression of a protein known as
GADD45a (Gene activated during DNA damage). Studies in humans
have shown the ability of curcumin to tilt the ratio of
pathogenic microbes and beneficial microbes. Curcumin, in fact,
may lower intestinal inflammation via regulating gut flora.
Curcumin was showed to reduce NF-κB activation in colonic
epithelial cells and increase the growth of CD4+ Foxp3+
regulatory T cells in the colonic mucosa in an experimental
DSS-colitis model. Another study revealed the effect of curcumin
consumed in diet could cause an increase in the species of
Clostridium, Enterobacter (have the potential to enhance
mucosal Treg cells by producing butyrate) and reducing the
levels of Blautia and Ruminococcus species
(which has been linked with individuals that has colorectal
cancer) that is present in abundance
The
Curcumin Supplementation with Piperine Can Influence the Acute
Elevation of Exercise-Induced Cytokines: Double-Blind Crossover
Study Biology | April 2022 The most
important findings of this study were the administration of
curcumin associated with piperine can inhibit the elevation of
plasmatic levels of some cytokines such as IL-2, TNF-α, IFN,
IL-6, and IL-10. This result shows the capacity of curcumin to
modulate an inflammatory response acutely induced by exercise.
Supplementation with 500 mg of curcumin associated with 20 mg of
piperine for seven days was able to inhibit the inflammatory
response after an experimental protocol of running on a
treadmill until voluntary fatigue.
The Golden Spice Curcumin in Cancer: A Perspective
on Finalized Clinical Trials During the Last 10 Years
Journal of Cancer Research and Therapeutics | April 2022
Curcumin is the main curcuminoid in turmeric and has been found
to possess various beneficial properties, including
anti-inflammatory, antioxidant, neuroprotective,,
chemopreventive, and chemotherapeutic, activities, which make
this phytocompound famous. Curcumin affects multiple signaling
pathways involved in cell proliferation, survival, cell death,
angiogenesis, invasion, migration, and metastasis. Cancer
preventive and anticancer therapeutic actions of curcumin
against different types of cancers, such as breast, liver,
melanoma, lung, and endometrium, are available in the
literature. Based on clinical trials in cancer patients, it was
concluded that even 8 g of curcumin was safe and well tolerated.
As a therapeutic agent, curcumin has been subjected to clinical
trials for various diseases, such as psoriasis, multiple
myeloma, chronic uveitis, pancreatitis, pancreatic, colorectal,
and biliary tract cancers, familial adenomatous polyposis,
inflammatory bowel disorder, Alzheimer's disease, and diabetes
mellitus. Various clinical trials investigated curcumin's
bioavailability, its effect on various cancer types, and the
efficacy of turmeric and curcumin in mitigating the side effects
of cancer chemotherapy and radiotherapy. We have presented 21
clinical trials, 16 of the 21 clinical trials were associated
with the effectiveness of curcumin on various types of cancer,
and the other 5 clinical trials were related to the
evaluation of the curcumin's efficacy in relieving the side
effects of cancer chemotherapy and radiotherapy. The emerging
data from clinical trials confirm that curcumin has considerable
potential to treat cancer patients. It is expected that findings
from ongoing and future clinical trials may help the clinical
application of curcumin in managing different types of cancer.
A Comprehensive Review on the Therapeutic Potential
of Curcuma longa Linn. in Relation to its Major Active
Constituent Curcumin Frontiers in
Pharmacology | April 2022 Curcumin has a variety of
beneficial effects on humans, according to science. Curcumin’s
efficacy, safety, and pharmacokinetics have all been examined
extensively in clinical studies over the last 50 years (Gupta et
al., 2013; Subramani et al., 2018). Cancer, CVD, arthritis,
atherosclerosis, diabetes, gastric illness, IBD, psoriasis,
acquired immunodeficiency syndrome, and other inflammatory
disorders are all examples of pleiotropic activities. Several
studies in this review discovered the anti-inflammatory effects
of curcumin, including decreased white blood cell, neutrophil,
and eosinophil numbers, as well as protective effects on serum
levels of inflammatory mediators like phospholipase A2 and total
protein in various inflammatory disorders. Curcumin has
anticancer properties by interfering with many cellular systems
and inhibiting/inducing the production of multiple cytokines,
enzymes, or IκKβ, TNF-α, STAT3, COX-2, PKD1, NF-κB, epidermal
growth factor, and MAPK, among others. Under oxidative stress
conditions, curcumin decreased MDA and NO levels while
increasing thiol, SOD, and catalase levels. Curcumin also
influenced the lifespan of organisms by regulating important
signaling pathways such as the mTOR, PKA, and FOXO signaling
pathways. In conditions where the immune system was disturbed,
treatment with C. longa and curcumin enhanced IgE, IL-4, TGF-β,
IL-17, IFN-γ, and the Th1/Th2 ratio. The pharmacological effects
of curcumin on respiratory, allergy, and immunologic problems
suggest that curcumin may have a possible therapeutic effect on
these illnesses. Curcumin delay the onset of diabetes, improve
β-cell functioning, prevent β-cell death, and reduce insulin
resistance in animal models.Traditional medicine has exploited
dried curcumin powder to treat illnesses in history. C. longa is
said to have antitoxic, anticancer, antibacterial,
anti-inflammatory, and antioxidant effects (Ghotaslou et al.,
2017). Rhizome powder is supposed to flavor various cuisines and
treat numerous disorders, including inflammation, flatulence,
jaundice, menstrual troubles, hematuria, and hemorrhage. It is
also a useful ointment to treat several skin disorders. Curcumin
or diferuloylmethane and numerous volatile oils. C. longa of
India is particularly popular when compared with those from
other countries due to its high curcumin concentration, which is
the most essential and active biological ingredient responsible
for its therapeutic potential (Verma et al., 2018). Curcumin
shows antioxidant features close to vitamins C and E in both
aqueous and fat-soluble extracts.
Effects of turmeric (Curcuma longa) and its
constituent (curcumin) on the metabolic syndrome: An updated
review Journal of Integrative Medicine |
April 2022 Based on studies, turmeric and its bioactive
component, curcumin, due to their anti-inflammatory and
antioxidant properties, have antidiabetic effects through
increasing insulin release, antihyperlipidemic effects by
increasing fatty acid uptake, anti-obesity effects by decreasing
lipogenesis, and antihypertensive effects by increasing nitric
oxide. According to several in vivo, in vitro and human studies,
it can be concluded that turmeric or curcumin has important
values as a complementary therapy in Metabolic syndrome. In
vitro and in vivo studies have proved that
curcumin has anticancer, anti-inflammatory, antioxidant and
anti-fat properties. Some studies have shown that curcumin has
protective effects against many chronic diseases, for example,
autoimmune disorders and pulmonary diseases. It has
cardioprotective effects due to its lipid-lowering properties.
In the last few years, much consideration has been paid to the
benefits of curcumin. It can inhibit the development of
atherosclerosis and also significantly reduce the serum levels
of triglyceride (TG) and low-density lipoprotein-cholesterol
(LDL-C). Also, curcumin can increase insulin sensitivity through
the inhibition of protein tyrosine phosphatase 1B. It has
antioxidant effects in the artery and also can decrease the
levels of reactive oxygen species (ROS) in the basilar artery
wall. It remarkably delayed the onset of stroke. Curcumin in
diabetic conditions decreased the levels of fast blood sugar,
uric acid, serum urea and creatinine. Curcumin significantly
alleviated the severity of liver fibrosis. Curcumin treatment
lowered the increased blood pressure. It also plays a
significant role in obesity and significantly decreases
adiposity. One of curcumin and turmeric anti-diabetic mechanisms
is decreasing the phosphorylation level of insulin and
inhibiting the activation of the NF-κB. Curcumin and turmeric
can treat hypertension by suppressing downregulation of eNOS.
Evaluation
of the Anti-Cancer Effect of Curcumin on MCF-7 Cells in 3D
Culture Conditions to Increase the Efficacy of Breast Cancer
Treatment Journal of Applied Biotechnology
Reports | April 2022 Curcumin reduces the production of
cellular NO and increases the production of catalase and
glutathione, which confirms the results of the NO test. In
addition, the release of cytochrome c from Mitochondria from
cells treated with different concentrations of curcumin compared
to control cells are significant. The evaluation of the toxicity
effect of curcumin at concentrations of 20, 40, and 80 μM using
comet assay showed that this substance induces apoptosis in
MCF-7 cells in a dose-dependent manner. The findings of this
study showed that the anti-cancer effect of curcumin on MCF-7
cells under 3D culture conditions could increase the
effectiveness of treatment. The cancer cell survival rate
actually depended on curcumin concentration.
Curcumin Alleviates DSS-Induced Anxiety-Like
Behaviors via the Microbial-Brain-Gut Axis
Oxidative Medicine and Cellular Longevity | April 2022 Curcumin
is a yellow polyphenol extracted from the rhizome of the ginger
plant, which has been shown to have effects against both
depression and anxiety. Research has indicated that curcumin
affects the gut microbiome and exerts antianxiety and
neuroprotective effects through the microbiota-gut-brain axis.
The results suggested that curcumin can effectively relieve
anxiety-like behaviors caused by DSS in mice. Further, curcumin
treatment can alleviate disturbances in the gut microbiota and
systemic disorders of lipid metabolism caused by DSS. Finally,
through FMT, we verified that curcumin increased
phosphatidylcholine in the prefrontal cortex of the mice and
alleviated DSS-induced anxiety-like behaviors by modulating
specific gut microbiota. We also revealed that
Muribaculaceae may be a key part of the gut microbiota for
curcumin to alleviate DSS-induced anxiety-like behaviors through
the MGB axis. Curcumin is also believed to hold medicinal
properties against many diseases, including gastrointestinal,
cardiovascular, and mental diseases. High concentrations of
curcumin have been detected in the gastrointestinal tract after
oral administration. Supplementation of curcumin significantly
enriched beneficial bacteria such as Butyricicoccus, a
butyrate producing genus in the intestinal tract, and reduced
Ruminococcus, and Mucispirillum, which were
implicated in the development of obesity and diabetes. These
findings were the basis to suggest that curcumin directly
affects the gut microbiome despite its low systemic
bioavailability. Curcumin can relieve inflammation and digestive
tract symptoms caused by IBD.
Curcumin induces cortico-hippocampal neuronal
reshaping and memory improvements in aged mice
Journal of Chemical Neuroanatomy | April 2022 Traditional
medicine has long benefitted from naturally occurring molecules
such as curcumin (diferuloymethane). Curcumin is extracted from
the plant Curcuma longa and is known for its synaptic and
antioxidant-related benefits. In this study, we tested the
hypothesis that chronic curcumin treatment reduces cognitive and
cellular effects of aging. Curcumin-treated mice showed improved
learning and memory using the Morris Water Maze and novel object
recognition task. In addition, using the Golgi-Cox stain,
curcumin treatment increased spine density in all evaluated
regions and increased dendritic arborization in the prefrontal
cortex (PFC) layer 3 and CA3 subregion of the hippocampus.
Moreover, chronic curcumin exposure increased synaptophysin and
actin expression and reduced glial fibrillary acidic protein
expression, a marker of astrocytes, in the hippocampus (CA1 and
CA3 subregions), while simultaneously reducing the ROS-related
molecule, metallothionein 3 expression in the PFC and
hippocampus. Collectively, these novel findings suggest that
curcumin reduces cognitive, neuronal and astrocytic signs
of aging in mice. Curcumin is the main metabolite found in
Curcuma longa with potential benefits in aging. Curcumin-treated
mice showed improved learning and memory in aged mice.
Curcumin treatment increased dendritic arborization in the PFC
and hippocampus. Curcumin exposure reduced astrocytic
expression in the hippocampus.
Curcumin
as a Potential Therapeutic Agent in Certain Cancer Types
Cureus Journal of Medical Science | March 2022
Several anticancer compounds have been extracted from plant
sources such as Curcuma longa. Among these, curcumin
(diferuloylmethane) has no noticeable toxicity and, in
combination with existing chemotherapeutic agents, is a superior
treatment option for certain cancer types. Curcumin is an
important component of the curcuminoids family and is isolated
from the rhizome of Curcuma longa L. (turmeric). The potential
applications of curcumin include the prevention and treatment of
cancer, anti-inflammatory/antioxidant, and antiangiogenic
activities. These beneficial effects of curcumin are exerted by
modulating signaling molecules, including cytokines, chemokines,
transcription factors, adhesion molecules, microRNAs, tumor
suppressor genes, etc. Several studies have shown the antitumor
activity of curcumin on breast cancer, prostate cancer, brain
cancer, lung cancer, and pancreatic cancer. Curcumin is a potent
anti-oxidative, anti-inflammatory, and anti-tumor agent, and it
is extracted from rhizomes of Curcuma species. Curcumin, as a
cancer treatment agent, is recognized to affect multiple targets
in different stages of cancer, including angiogenesis,
proliferation, metastasis, and apoptosis. The molecular
mechanism of action of curcumin has been studied
comprehensively. It exerts this effect by interfering with
several cell-signaling pathways as well as inducing and
inhibiting the production of various growth factors, enzymes, or
cytokines. Structural and chemical modifications have been tried
to enhance the selectivity, bioavailability, and efficacy of
curcumin for cancer. Its therapeutic effects for the breast,
lung, prostate, intestinal, liver, and hematological
malignancies have been proven in the pre-clinical as well as in
vivo studies.
An Update on the Exploratory Use of Curcumin in
Neuropsychiatric Disorders Antioxidants |
March 2022 Curcumin, the active compound of turmeric, is a
polyphenol that has also been largely used as a remedy for
different pathologies in Asia for several decades due to its
healthy and biopharmacological properties, and its lack of
adverse effects, even at high doses. Moreover, curcumin has been
reported to have anti-inflammatory, antioxidant,
neuroprotective, and even anti-aging and antineoplasic
properties. Curcumin may exert its anti-inflammatory and
antioxidant (anti-IOS) effects by influencing the synthesis of
some IOS regulators, such as heme-oxygenase-1 (HO1), glutathione
(GSH), catalase (CAT), and superoxide dismutase. These
properties cause curcumin to have an impact on those diseases in
which IOS regulation does not work correctly and are related to
the disease appearance. Thus, curcumin may exert a beneficial
effect on the immune system, reducing B lymphocyte proliferation
by inhibiting B lymphocyte stimulator (BLYS). Curcumin can also
reduce the neutrophil recruitment to areas affected by
inflammation, and can also increase the phagocytic activity of
macrophages. Furthermore, curcumin has proven to be an effective
modulator of the endocrine system, enhancing the uptake or
regulating some hormones, such as insulin. All these properties
have boosted the interest of researchers in this compound in
recent decades. Recently, curcumin has also been used in
different psychiatric disorders due to the likely involvement of
IOS processes in their onset and evolution. In this sense, the
above-described role of curcumin as an anti-IOS drug made this
compound a good candidate to halt or palliate the course of
these diseases. Anti-inflammatory, antioxidant, and
neuroprotective properties of curcumin, along with many
multi-target beneficial effects, such as the modulation of
monoamine synthesis, have exponentially promoted the
investigation of its properties during this last decade.
Two-hundred and ninty-six articles containing research on
curcumin were published in the PubMed database in 2005. In 2010,
this number increased to 714 and, in 2020, to 2130. A total of
65 preclinical studies and 14 clinical trials were reported.
Most of these studies were conducted on depression,
approximately 88% were preclinical studies and 64% were clinical
studies. In all disorders, curcumin was well tolerated, with no
harmful side effects. This was not surprising, as curcumin has
been used for the last centuries as an additive spice in East
Asian cuisine. Moreover, curcumin was shown to be beneficial in
palliating or reversing symptoms associated with psychiatry in
all the studies analyzed and completed. In clinical trials,
curcumin proved to be effective in alleviating both positive and
negative symptoms of schizophrenia when administered together
with regular antipsychotic medication. The clinical relevance of
these results could be of great importance, due to the adverse
events that can be caused by the extensive and chronic use of
antipsychotics. In this sense, curcumin could exert its
beneficial effect in schizophrenia through an inhibition of PLA2
enzyme. In depression, we found the vast majority of studies, in
both preclinical and clinical domains, showed some beneficial
effect of curcumin in reducing symptoms associated with
depression. In addition to the recognized role of curcumin as an
anti-inflammatory and antioxidant agent, positive improvement of
depressive deficits could be exerted through modulation of the
indolamine 2,3-dioxygenase (IDO) enzyme. Therefore, the overall
effect of curcumin in this disorder seems to be mainly positive.
Overall, curcumin, due to its anti-inflammatory and antioxidant
properties, has been shown to be effective in the vast majority
of the studies presented.
Curcumin-Rich
Curry Consumption and Neurocognitive Function from 4.5-Year
Follow-Up of Community-Dwelling Older Adults
Nutrients | March 2022 Curcumin is a polyphenolic compound
isolated from the roots of Curcuma longa, from which turmeric is
prepared and used widely as a coloring agent, food additive and
traditional Indian and Chinese medicine. For decades, curcumin
and related bioactive curcuminoids (demethoxycurcumin and
bisdemethoxycurcumin) have been the center of interest of
scientific studies worldwide into their therapeutic potentials.
Numerous laboratory studies have documented its antioxidant,
anti-inflammatory, antimicrobial, antiviral, antineoplastic and
antiaging activities. Curcumin is actively being investigated
for its potential neuroprotective benefits. In vitro and in vivo
studies show that curcumin crosses the blood–brain barrier and
can bind to β amyloid (Aβ) and tau-inhibiting Aβ aggregation and
modulate tau processing. Animal studies show that curcumin
decreases Aβ deposition and plaque load in the brain of
transgenic mouse models of AD. Experimental studies have also
demonstrated that curcumin possesses beneficial antiplatelet,
antidiabetic and cardioprotective activities ameliorating
cardiac hypertrophy and chronic heart failure. On top of the
known anti-inflammatory activities of curcumin attenuating
neuroinflammation, this experimental evidence strongly suggests
that curcumin has the potential to prevent accelerated cognitive
decline in humans. Several animal studies have shown that
curcumin improves cognitive function. Randomized controlled
trials in humans are limited but suggest that curcumin could be
safely and effectively used to slow cognitive decline. We found
in this observational cohort study that the consumption of
curcumin-rich curry in food was associated with the maintenance
of higher levels of cognitive functioning over time among
community-dwelling middle-aged and older Asian adults in
Singapore. To our knowledge, this is the first longitudinal
study demonstrating the cognitive benefits of curcumin from
natural dietary food sources in humans. Curcumin exposure from
dietary ingestion appears to offer neuroprotection especially
through its beneficial metabolic, antiplatelet and
cardioprotective properties. There is evidence that the
combination of piperine in black pepper with curcumin in
turmeric increases the bioavailability of curcumin by 2000% and
inhibits the intestinal and hepatic glucuronidation of curcumin.
In this study, real-world observations of the potential
cognitive benefits of curcumin in humans were provided in a
large population-based cohort of community-dwelling older adults
with follow-up over three to five years. The consumption of
dietary curcumin was associated with the maintenance over time
of higher functioning on attention, short-term working memory,
visual spatial constructional ability, language and executive
function among community-dwelling older adults. This suggests
that, notwithstanding its known anti-amyloid, anti-tau,
antioxidant and anti-inflammatory activities, curcumin exposure
from dietary ingestion appears to offer neuroprotection
especially through its beneficial metabolic, antiplatelet and
cardioprotective properties. The results from the stratified
analysis support this by showing that among participants with
pre-existing metabolic and cardiovascular disease, curry
consumption was associated with enhanced performance on
attention, working memory and language executive function. In
vitro and high-dose animal studies show that curcumin modulates
molecular pathways that restore glucose homeostasis, lipid
metabolism, endothelial function and insulin signaling and may
thus offer potential cardiovascular protective effect. These observations
suggest that population health in terms of healthy cognitive
ageing and potential reduction of risks of dementia could be
enhanced by increased consumption of curcumin in a turmeric-rich
diet.
Potential Role of Curcumin for the Treatment of
Major Depressive Disorder CNS Drugs | March 2022 Curcumin is the major biologically active
polyphenolic constituent in the turmeric plant (Curcuma longa)
that has been shown to have antioxidant, anti-inflammatory,
neuroprotective, anticancer, antimicrobial, and cardioprotective
effects. Interest in curcumin as a treatment for mental health
conditions has increased and there is an expanding body of
preclinical and clinical research examining its antidepressant
and anxiolytic effects. Cell culture and animal studies have
demonstrated that curcuminoids, and in particular curcumin, have
extensive biological activity, including antioxidant,
anti-inflammatory, neuroprotective, anticancer, antimicrobial,
and cardioprotective effects. Turmeric has traditionally been
used in Indian folk medicine to treat eye infections, skin
wounds, respiratory conditions and digestive complaints, and to
reduce general inflammation. More recently, interest in curcumin
as a treatment for depression has increased and there is an
expanding body of research confirming antidepressant and
anxiolytic effects from its administration. There is an
increasing body of research supporting the efficacy of curcumin
as a treatment for depression. Positive antidepressant
effects were reported in six of seven trials, with the only
non-significant finding identified by Bergman et al., where
curcumin was used as an adjunct to pharmaceutical
antidepressants and administered for the shortest treatment
period of all the trials (5 weeks). Positive anxiolytic effects
from curcumin administration were also identified in four
trials. Interestingly, in this meta-analysis, an even larger
treatment effect was identified when examining the effects of
curcumin on anxiety symptoms (Hedge’s g = 2.62). In a
meta-analysis conducted in 2016, it was concluded from subgroup
analyses that curcumin had the highest antidepressant effects
when administered to middle-aged adults, for longer treatment
periods, and at higher doses.
Investigation
of the Effect of Curcumin on Protein Targets in NAFLD Using
Bioinformatic Analysis Nutrients | March
2022 Curcumin is a bioactive polyphenolic compound, isolated
from Curcuma longa Linn, which is endowed with diverse
pharmacological activities. Curcumin improves steatosis,
inflammation, and fibrosis progression. Curcumin may
improve, or inhibit, progression of non-alcoholic fatty liver
disease (NAFLD)through activation/inhibition of non-alcoholic
fatty liver disease (NAFLD)-related genes. Numerous in-vitro and
in-vivo investigations have indicated that curcumin exerts a
positive effect at each stage of non-alcoholic fatty liver
disease (NAFLD), improving both inflammation and the extent of
fat deposition. Curcumin was also shown to inhibit the
progression from non-alcoholic fatty liver disease (NAFLD) to
fibrosis and decrease the risk of liver cancer. Emerging from
these studies, therefore, are data supporting the significant
clinical effect of curcumin on non-alcoholic fatty liver disease
(NAFLD). Curcumin exerts its anti-diabetic, cardioprotective,
hepatoprotective, neuroprotective, and antitumor effects via
NFE2L2 signaling pathways. Curcumin activates NFE2L2 signaling
pathways in four ways. In a high-fat and high-fructose diet (HFHFr)
mouse model, NFE2L2 was downregulated, while curcumin
administration could reverse the abnormal serum biochemical
parameters of hepatic steatosis. Another animal study using
carbon tetrachloride (CCL4) induced liver damage showed that
curcumin’s protective role in reducing inflammation and
oxidative stress was mediated through NFE2L2/HO-1 pathways. An
in-vitro study showed that curcumin, through activation of
NFE2L2, can promote lipocyte activation in stellate cells (HSCs)
and repress hepatic fibrosis. In this study, we identified 14
genes in non-alcoholic fatty liver disease (NAFLD) that are
likely to be the target of curcumin and observed that curcumin
induces or inhibits them. According to our results, this
activity of curcumin was in line with improving non-alcoholic
fatty liver disease (NAFLD) based on literature. We believe that
the ongoing clinical trials investigating the effect of curcumin
on fatty liver could yield positive results in the future,
enhancing the therapeutic status of curcumin in this metabolic
disorder.
Molecular
Targets of Curcumin and Its Therapeutic Potential for Ovarian
Cancer Nutrition and Cancer | March 2022
Curcumin is a natural product found in the rhizome extract of
Curcuma longa and has been extensively used over the last
decades for its unique biological and medicinal properties,
which include: having antioxidant, analgesic, anti-inflammation,
and anti-tumor activities. Curcumin exerts its anticancer
properties against ovarian cancer via multiple mechanisms:
interfering with cellular interactions necessary for metastasis
and recurrence of OC cells, increasing pro-apoptotic proteins as
well as inducing or suppressing generation of different
molecules such as cytokines, transcription factors, enzymes,
protein kinases, and growth factors. Moreover, curcumin
down-regulates various signaling pathways such as PI3K/Akt,
Wnt/β-catenin, JAK/STAT3, and MEK/ERK1/2 axes, which at least in
part have a role in inhibiting further tumor proliferation,
growth, and angiogenesis. In this review, we overview the
potential of incorporating curcumin into the treatment of
ovarian cancer.
Curcumin in Combination with Aerobic Exercise
Improves Follicular Dysfunction Oxidative
Medicine and Cellular Longevity | March 2022 Curcumin is a
natural medicine containing phenol and quinone groups extracted
from turmeric in the ginger family. It is well known as a safe
dietary supplement worldwide. In several randomized,
double-blinded, clinical trial, patients with PCOS received
curcumin (in doses of 500-1500 mg 3 times daily for 1-3 months)
or placebo. It is suggested that curcumin can effectively
improve blood glucose, insulin resistance, and hyperandrogenemia
in PCOS. Moreover, curcumin reportedly exerts numerous
biological effects to manage human diseases, including cancer
and neurodegenerative and metabolic disorders. Both curcumin
gavage and aerobic exercise improved ovarian function.
Curcumin and aerobic exercise (irisin) can alleviate
hyperandrogenism-induced ER stress and suppress the IRE1α-XBP1
pathway, which prevented ovarian GC apoptosis in PCOS-like rats,
leading to the improvement in the ovarian microenvironment and
promotion of follicular development.
Curcumin
Suppresses Lead-Induced Inflammation and Memory Loss in Mouse
Model and In Silico Molecular Docking
Foods | March 2022 Curcumin is a polyphenol primarily
extracted from turmeric, and has drawn much attention in the
field of natural drug discovery due to its excellent therapeutic
effects, such as its antioxidant, anti-inflammation,
anti-microbial, anti-arthritic, and anti-depressant activities.
In addition, curcumin can modulate cognitive dysfunction and
astrocyte proliferation. Research revealed that curcumin can
suppress memory impairment and can attenuate cognitive deficits.
In mercury chloride-treated offspring mice, curcumin treatment
improved memory and learning activity, antioxidant profile, and
increased AChE, serotonin, and dopamine. Curcumin also
downregulated the AChE gene expressions. Curcumin is known
to have a potent antioxidant activity due to its capacity for
chain-breaking, as well as the hydrogen-donating phenolic groups
in its structure. Much research has also revealed the
neuroprotective effects of curcumin, which operate via exerting
antioxidant effects and reducing oxidative damage. Curcumin
exhibits great promise as a therapeutic agent for a variety of
cancers, as well as for psoriasis, and Alzheimer’s disease. It
has been reported that curcumin suppresses aluminum- and Pb-induced
oxidative neurotoxicity, alterations in NMDA receptors that lead
to decreased antioxidant enzyme activity, and AChE dysfunctions.
Thus, the present study has indicated that curcumin, a potent
antioxidant compound, ameliorated lipid peroxidation and
oxidative stress parameters in mice exposed to Pb, along with
protecting against cholinergic dysfunction. Curcumin
co-treatment effectively suppresses Pb-induced brain
inflammation. Thus, Curcumin may completely bind with AchE to
increase enzymatic activity, which is predicted to have
dose-dependent neuroprotective effects, at least in part via
exerting antioxidant and anti-inflammatory effects, and
reversing the Pb-induced alterations in transmitters and
enzymes.
Cardioprotective effects of exercise and curcumin
supplementation against myocardial ischemia–reperfusion injury
Sport Sciences for Health | March 2022 Exercise and curcumin
individually provided cardioprotective effects against
ischemia–reperfusion-induced injury which appears to be
associated with an attenuation in mRNA expression of β-amyloid
peptide precursor in addition to processing enzymes and an
increase in mRNA expression of neprilysin.
Curcumin Inhibits Papillary Thyroid Cancer Cell
Proliferation Analytical Cellular
Pathology | March 2022 Curcumin is a polyphenolic compound
and a member of the Zingiberaceae (ginger) family derived from
turmeric plants. It has been extensively used in Chinese
medicine to treat various diseases, including inflammation and
cancer. Curcumin was found to participate in the process of
pancreatic cancer, colorectal cancer, and hepatocellular cancer
by regulating specific lncRNAs and miRNAs. In addition, curcumin
can suppress PTC cell metastasis. Curcumin was shown to enhance
the anticancer activity of cisplatin in PTC cells and cancer
stem-like cells by regulating the JAK/STAT3 signaling. In
conclusion, the present study provides evidence that curcumin
promotes apoptosis and inhibits proliferation and the Warburg
effect by inhibiting LINC00691 in B-CPAP cells. Moreover, the
specific molecular mechanism might be mediated through the Akt
signaling pathway. This study provides a theoretical basis for
the treatment of PTC with curcumin.
Curcumin
as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs
in Breast Cancer International Journal of
Molecular Sciences | February 2022 Collectively, curcumin in
combination with chemotherapy drugs may improve their clinical
application in breast cancer therapy, and it is of considerable
value to develop as an adjunct for combination chemotherapy with
current drugs to treat breast cancer. Curcumin is an ideal
chemopreventive and chemotherapy agent owning to its
multitargeting function on various regulatory molecules, key
signaling pathways, and pharmacological safety. This review
aimed to elucidate the potential role of curcumin in enhancing
the efficacy of doxorubicin, paclitaxel, 5-fluorouracil, and
cisplatin via combinational therapy. Additionally, the molecular
mechanisms underlying the chemosensitizing activity of these
combinations have been addressed. Overall, based on the
promising therapeutic potential of curcumin in combination with
conventional chemotherapy drugs, curcumin is of considerable
value to develop as an adjunct for combination chemotherapy with
current drugs to treat breast cancer.
Effects of curcumin supplementation on metabolic
parameters, inflammatory factors and obesity values in women
with rheumatoid arthritis: A randomized, double-blind,
placebo-controlled clinical trial
Phytotherapy Research | February 2022 Curcumin
supplementation significantly decreased homeostatic model
assessment for insulin resistance (HOMA-IR), erythrocyte
sedimentation rate, serum levels of high-sensitivity C-reactive
protein and triglycerides, weight, body mass index, and waist
circumference of patients compared with the placebo at the end
of the study (p < .05 for all). HOMA-IR and triglyceride levels
significantly increased within the placebo group.
Curcumin induces autophagic cell death in human
thyroid cancer cells Toxicology in Vitro |
February 2022 Curcumin acts as an autophagy inducer on many
cancer cells. In the present study, curcumin significantly
inhibited the growth of thyroid cancer cells. Autophagy was
markedly induced by curcumin treatment as evidenced by an
increase in LC3-II conversion, beclin-1 accumulation, p62
degradation as well as the increased formation of acidic
vesicular organelles (AVOs). 3-MA, an autophagy inhibitor,
partially rescued thyroid cancer cells from curcumin-induced
cell death. Additionally, curcumin was found to exert selective
cytotoxicity on thyroid cancer cells but not normal epithelial
cells and acted as an autophagy inducer through activation of
MAPK while inhibition of mTOR pathways.
Effect
of Curcumin in Experimental Pulmonary Tuberculosis:
Antimycobacterial Activity in the Lungs and Anti-Inflammatory
Effect in the Brain International Journal
of Molecular Sciences | February 2022 Curcumin is a natural
product with antioxidant, anti-inflammatory and antibacterial
activities. Curcumin is a polyphenolic compound obtained from
the rhizomes of Curcuma longa, a rhizomatous native plant from
South and Southeast Asia that belongs to the family
Zingiberaceae. Research has revealed that curcumin has
pleiotropic properties, including anti-inflammatory,
antioxidant, chemopreventive, chemotherapeutic activity,
neuroprotective properties, and antibacterial activity. The
pleiotropic actions of curcumin are derived from its complex
chemistry and its ability to influence multiple signaling
pathways. Curcumin controls the inflammatory response by
downregulating the activity of the enzymes cyclooxygenase-2
(COX-2), lipoxygenase, and inducible nitric oxide synthase
(iNOS). In addition, curcumin suppresses the activation of
nuclear factor kappa B (NF-κB) activation; inhibits the
production of the inflammatory cytokines TNF-α, interleukin
(IL)-1, -2, -6, -8, and -12, monocyte chemoattractant protein
(MCP) and migration inhibitory protein; and down-regulates
mitogen-activated and Janus kinases. In addition, curcumin
protects the brain from damage through the upregulated
expression of the transcription factor, the nuclear factor
erythroid 2-related to factor 2 (Nrf2) expression, and the
hippocampal levels of brain-derived neurotrophic factor (BDNF).
Indeed, there is evidence that curcumin has a beneficial effect
on humans suffering from depression and anxiety, linked to
curcumin anti-inflammatory effects, dopamine release,
antioxidant activity, and neurotrophic factor regulation.
Curcumin also resulted in a dose-dependent increase in
hippocampal BDNF in a model of depression. These data coincide
with our results, where we observed a significant increase in
BDNF levels in the hippocampus of animals with TB treated with
curcumin, related to the beneficial effect of curcumin on
memory and the decrease in depression-like behavior in this
model. Curcumin protected from injury in a model of an ischemic
brain through the Akt/Nrf2 pathway. Curcumin has a
neuroprotective effect in a model of traumatic brain injury
(TBI) associated with activating the Nrf2 pathway. These data
suggest that treatment with curcumin has a beneficial effect on
various neuroinflammatory and neurodegenerative diseases,
including those related to pulmonary TB. This investigation
revealed the efficacy of curcumin administration as a novel
treatment for controlling neuroinflammation in chronic
infectious diseases such as pulmonary TB. In addition, it is
worth noting that curcumin had a therapeutic effect on lung
disease, indicating that curcumin might be used as a coadjuvant
treatment in TB chemotherapy.
Curcumin Ameliorates Cardiac Fibrosis
Frontiers in Pharmacology | February 2022 The
therapeutic potential of curcumin has been widely investigated,
including its utilization in various of cardiovascular diseases.
Curcumin’s health benefits has been well-established, including
anti-tumor, anti-viral, anti-oxidative stress,
anti-inflammatory, anti-microbial, hypoglycemic etc.
Therapeutically, curcumin exhibits promising potential in
preclinical as well as clinical studies and is currently in
human trials for a variety of conditions, including metabolic
syndrome, nonalcoholic fatty liver disease, atherosclerosis,
liver cirrhosis, depression, psoriasis, and Alzheimer’s disease
(Kocaadam and Şanlier, 2017). The immunomodulatory functions of
curcumin arise due to its interactions with cellular and
molecular components during inflammatory reactions. Dietary
exposure to 40 mg/kg curcumin for 5 weeks showed enhanced IgG
levels in rats, suggesting an improvement in immune function
after curcumin intervention (South et al., 1997). Curcumin has
also been shown to regulate macrophage polarization by
increasing the M2 phenotype marker CD163 together with the
anti-inflammatory cytokine IL-10 and decreasing the M1 phenotype
marker CD86 along with the pro-inflammatory cytokines TNF-α and
IL-6 (Li et al., 2017). Curcumin significantly ameliorated the
inflammation process subsequent to myocardial infarction,
reflected by decreased expression of CD68+ and CD3+ cells,
accompanied by dramatically improved cardiac function compared
with the placebo group. In addition, cardiac fibrosis is
inhibited by curcumin administration. Mechanistically, we
discovered that curcumin significantly downregulated
pro-inflammatory cytokines in macrophages. Curcumin improves
cardiac function and reduces cardiac fibrosis after myocardial
infarction. Curcumin has roles in various cardiovascular
diseases, including ischemic heart, pressure overload heart, and
metabolic disorder-related cardiac diseases. It is
well-established that curcumin can directly exerts
cardio-protective effect by targeting cardiomyocyte through
various of signaling pathway, like disrupts the p300/GATA4
complex and represses agonist-and p300-induced hypertrophic
responses in cardiomyocytes (Morimoto et al., 2008)or activates
the autophagy by upregulating AMPK and JNK1 to alleviate the
apoptosis of cardiomyocytes under ischemic stimulation (Yao et
al., 2018). In summary, our study revealed that the
administration of curcumin significantly ameliorated
inflammation in the acute phase, as reflected by the promotion
of macrophage apoptosis, accompanied by decreased
pro-inflammatory cytokine secretion, including IL-6, IL1b, and
TNF-α. These findings suggest that curcumin has potential
as a potent therapeutic target in treating adverse remodeling in
ischemic heart disease.
Curcumin sensitizes response to cytarabine in acute
myeloid leukemia by regulating intestinal microbiota
Cancer Chemotherapy and Pharmacology | February 2022 Curcumin
is a natural phenolic compound extracted from curcuma longa,
which exerts a wide range of biological effects, such as
anti-tumor, anti-inflammatory, anti-oxidation and anti-fibrosis.
Moreover, Curcumin was also reported to affect energy metabolism
to increase energy expenditure as well as improve insulin
sensitivity in obese mice]. Energy metabolism also plays crucial
roles in response to chemotherapy. Several studies have reported
that targeting energy metabolism could sensitize resistant cells
to chemotherapy, such as oxidative phosphorylation inhibitor
redirected metabolism toward glycolysis to sensitize resistant
cells to cytarabine (Ara-C) in AML. Curcumin could affect
intestinal microbiota to prevent renal failure. Conversely,
intestinal microbiota could also enhance the effect of Curcumin
in ameliorating HFD-induced obesity by enhancing Ucp1-dependent
thermogenesis through regulating bile acids metabolism,
suggesting the interaction between intestinal microbiota and
Curcumin in curing diseases. Curcumin resulted in strengthening
intestinal intact, leading to reduced transfer of bacteria (or
their metabolites) to the blood, causing SQLE inhibition. In
conclusion, we demonstrated that Curcumin sensitizes response to
Ara-C by regulating microbiota and strengthening intestinal
intact is promising in chemoresistant therapy.
Curcumin supplementation in the rhesus monkey: effects on
cognitive decline and neuroinflammation
Boston University Theses & Dissertations | February 2022
Curcumin, the active ingredient in turmeric, is a polyphenol
nutraceutical with potent anti-inflammatory and antioxidative
effects. Several ongoing research studies are underway to
explore this potential anti-aging compound. Curcumin treatment
improved performance on object reversal testing, with treated
monkeys making fewer perseverative type errors. We demonstrated
that curcumin treatment did affect morphological features of
microglia specifically within the while matter. Within the white
matter, curcumin treatment was associated with a significant
increase in microglial ramification, evidenced by greater
process length, number of nodes and convex-hull area and volume.
Increased microglial ramification suggests greater likelihood of
microglial surveillance within the white matter associated with
curcumin treatment. While our findings show the benefit of
curcumin supplementation on cognitive performance and its
effects on microglial morphology, further study is needed to
understand the precise changes that curcumin supplementation may
have on inflammation.
Protective Effects of Curcumin in Cardiovascular Diseases—Impact
on Oxidative Stress and Mitochondria Cells
| February 2022 In this review, we will highlight the impact
of curcumin on age-related cardiovascular dysfunction, adipose
tissue, and obesity, as well as its protective effects in
atherosclerosis and myocardial infarction. Curcumin can
positively affect different risk factors for CVDs and the
outcome in the diseases themselves which has been shown in a
number of animal models. More importantly, it is effective
against cardiovascular diseases and has shown a promising impact
on cardiovascular diseases in clinical studies. Already more
than 20 years ago, it was shown that piperine, an alkaloid
responsible for the pungency of black pepper, dramatically
increases the serum levels of curcumin in rats and humans.
A New Perspective on the Treatment of Alzheimer’s
Disease and Sleep Deprivation-Related Consequences: Can Curcumin
Help? Oxidative Medicine and Cellular
Longevity | February 2022 Curcumin, a natural compound
isolated from C. longa, has multiple applications in
treatment of various diseases such as cardiovascular diseases,
liver disease, obesity, cancer, inflammatory diseases, and
aging. Besides these applications and activities, curcumin has
been reported to be effective in many neurodegenerative
diseases. Studies have shown that curcumin can lead to many
improvements in the pathological process of Alzheimer’s disease.
Its mechanisms of action can be classified as (I) sustaining
homeostasis of the inflammatory system, (II) increasing the
clearance of toxic substances from the brain, (III) scavenging
free radicals and inducing antioxidant elements, and (IV)
binding and limiting aggregation of misfolded proteins. In
addition to the effects of curcumin on neurodegenerative
diseases, especially Alzheimer’s disease, it has been reported
that curcumin can be beneficial in the management of sleep
deprivation (SD) and SD-induced neurological consequences as
well. The effects of curcumin on the medial prefrontal cortex (mPFC),
the protective potential on the dendritic trees from shortening
and shedding induced by chronic SD, and the effects of
SD-induced memory impairments have been demonstrated by in vivo
studies.
Curcumin
protects rats against gentamicin-induced nephrotoxicity by
amelioration of oxidative stress, endoplasmic reticulum stress
and apoptosis Pharmaceutical Biology |
February 2022 Curcumin is a major yellow phenolic pigment of
turmeric that is extracted from rhizome of Curcuma longa L.
(Zingiberaceae), a spice widely cultivated in tropical countries
in south and southeast Asia, such as China, India and Thailand (Wanninger
et al. 2015). Numerous studies have shown that curcumin has
excellent antioxidant and anti-inflammatory properties. It has
the ability to inhibit free radical generation, scavenge ROS and
induce an antioxidant response. Moreover, curcumin has also
exerted renoprotective effects in several experimental models,
including diabetic nephropathy, chronic renal failure, ischaemia
and reperfusion; it also combats nephrotoxicity protecting
against renal injury from oxidative stress (Trujillo et al.
2013). Interestingly, curcumin treatment helps protect
against acute myocarditis by inhibition of cardiac oxidative and
ER stress-mediated apoptosis (Mito et al. 2011). Curcumin
eliminates the hydroxyl radical, superoxide radical, singlet
oxygen, nitrogen dioxide and NO (Ruby et al. 1995; Sreejayan and
Rao 1997) and has been shown to inhibit hydrogen peroxide
induced oxidative injury in a renal cell line (Farombi and Ekor
2006) and prevented reduced activity of antioxidant enzymes
including glutathione peroxidase and SOD in rat remnant kidney
(Tapia et al. 2012). These results demonstrated that curcumin
inhibited oxidative stress and restoration of the antioxidant
enzymes leading to improved renal function and rescued kidney
damage in GM-induced nephrotoxicity. These results were in
line with the previous report demonstrating that curcumin
ameliorated high glucose-induced neural tube defects by
suppressing ER stress, caspase activation and apoptosis (Afrin
et al. 2015). Moreover, curcumin treatment also prevented cell
death induced by H2O2 (Wang et al. 2016). It might be suggested
that curcumin attenuated ER stress-induced apoptosis in
GM-induced nephrotoxicity, probably associated with the
antioxidative activity. The GM-induced nephrotoxicity was
contributed by the increasing of oxidative stress, ER stress
activation which eventually resulted in the apoptosis cell
death. These events were restored by the pre-treatment of
curcumin based on its activities to reverse several hallmarks of
nephrotoxicity. These findings emphasized the potential
therapeutic use of curcumin to be developed as an alternative
treatment for nephrotoxicity.
Neuroprotective effects of curcumin on the
cerebellum in a rotenone-induced Parkinson’s Disease Model
CNS Neuroscience & Therapeutics | February 2022 Curcumin has
a lipophilic property, can pass through cell membranes, and
exerts intracellular effects. Curcumin crosses the blood brain
barrier and is also detected in cerebrospinal fluid. The
strong antioxidant properties of curcumin scavenge reactive
oxygen species and inhibit lipid peroxidation. In one study,
administration of curcumin improved behavioral alterations,
oxidative damage, and mitochondrial enzyme dysfunction induced
by the administration of rotenone in mice. Curcumin also
restored electrical activity in the hippocampus altered by
rotenone. Curcumin is a strong antioxidant that minimizes
oxidative stress in vivo and in vitro. Curcumin exerts various
beneficial effects in treating and preventing neurodegenerative
diseases, such as stroke and Alzheimer's disease. Additionally,
several studies demonstrated curcumin's ability to inhibit key
Parkinson's disease-associated features, including ROS
formation, apoptosis, cytokine production, oxidative damage, and
cognitive impairment in cell lines and experimental animals.
Moreover, Khuwaja et al. demonstrated that curcumin helps stop
Parkinsonism and has therapeutic potential. Based on the results
of this study, rotenone causes Purkinje cell death and
astrogliosis by increasing oxidative stress in the cerebellar
cortex. Administration of curcumin prevented these effects.
Furthermore, cholinergic neurotransmission alterations induced
by rotenone were suppressed by curcumin, thus confirming the
behavioral and histological findings. This shows that curcumin
attenuated the neurotoxic effects and degenerative histological
changes in the cerebellar cortex and alleviated oxidative stress
in a Parkinson's disease rat model. Thus, curcumin could
have a role in therapeutic strategies for cerebellar affection
related to Parkinson's disease.
Supplements immunologist takes every day to
strengthen immune system CNBC | February
2022 Curcumin is the main active ingredient in turmeric root
and has been shown to bestow multiple health benefits. In fact,
there are more than 120 human clinical trials showing the
effectiveness of curcumin in treating diseases ranging from
autoimmunity to Alzheimer’s disease. The magic of curcumin is
how it decreases inflammation at multiple levels in the body,
not only helping with symptom relief from pain and arthritis but
also blocking inflammatory cytokines driving autoimmune disease,
heart disease and diabetes. It also improves the health of our
gut bacteria, which adds to our overall immune health. Because
curcumin is not absorbed well and one would have to eat copious
amounts of turmeric root to have significant benefits, I
recommend supplementing with 1,000 milligrams per day with food.
Curcumin
alleviates hepatic steatosis by improving mitochondrial function
in postnatal overfed rats and fatty L02 cells through the SIRT3
pathway Food & Function | February 2022
It was concluded that postnatal overfeeding damaged
mitochondrial biogenesis and antioxidant response, and increased
hepatic lipids and the severity of high-fat-induced NAFLD, while
curcumin alleviated hepatic steatosis, at least partially, by
enhancing mitochondrial function through SIRT3.
Therapeutic Applications of Curcumin in Diabetes: A
Review and Perspective BioMed Research
International | February 2022 The curcumin molecule exhibits
a multitargeting ability in various pathological conditions,
which allows translation into a therapeutic or nutraceutical
agent. Curcumin can support balance for oxidative and
inflammatory conditions, metabolic syndrome, arthritis, anxiety,
and hyperlipidemia. Curcumin has antioxidant, antiamyloid,
antimicrobial, antineoplastic, immune-modulating, and
neuroprotective effect. Curcumin also showed antidepressant
activity through modulating the release of serotonin and
dopamine. Diabetics are not able to metabolize well glucose due
to defects in insulin secretion and/or action, and curcumin is
capable to exert a therapeutic effect playing a critical role on
β-cell functions. Several studies have been shown the high
therapeutic properties of curcumin in hyperglycemia, diabetic
wound healing, diabetic neuropathy, diabetic cardiomyopathy, and
diabetic retinopathy and cataract.
Curcumin supplementation in pediatric patients: A
systematic review of current clinical evidence
UWA Medical School | February 2022 This systematic review was
designed to determine the clinical efficacy and safety of
curcumin supplementation for pediatric patients based on
clinical trials in children. We systematically searched
electronic databases including PubMed, EMBASE, Web of Science,
and Scopus for all studies that investigated curcumin
administration in the pediatric population without any time
frame limitation. Finally, we identified 16 studies for this
review. Clinical efficacy and safety of curcumin were assessed
in children with inflammatory and immune disorders (including
asthma, inflammatory bowel disease (IBD), and juvenile
idiopathic arthritis (JIA)), metabolic disorders, autosomal
dominant polycystic kidney disease (ADPKD), cystic fibrosis
(CF), tetralogy of Fallot (TOF), and infectious diseases.
Curcumin was administered in a wide range of doses (45 mg-4,000
mg daily) and durations (2-48 weeks). Overall, curcumin was well
tolerated in all studies and improved the severity of
inflammatory and immune disorders and metabolic diseases.
However, more studies are needed to clarify the role of curcumin
supplementation among children with ADPKD, CF, TOF, and
infectious diseases.
Effect of curcumin on body mass index and glycemic
indices in females with PCOS: a systematic review and
meta-analysis of randomized controlled trial
Nutrition & Food Science | February 2022 Random-effects
meta-analysis showed significant effects of curcumin on fasting
blood sugar (FBS) (−3.62 mg/dl, 95% CI [−5.65, −1.58], p-value <
0.001, I2 = 0.0%), insulin level (−1.67 µU/mL, 95% CI [−3.06,
−0.28], p-value = 0.018, I2 = 0.0%) and homeostasis model of
assessment insulin resistance (HOMA-IR) (−0.42, 95% CI [−0.76,
−0.09], p-value < 0.01, I2 = 0.0%).
A Plethora of Actions of Curcumin - A Magical Agent
for Treatment of Wide Range of Diseases Varying from
Neuroinflammatory Disease (Alzheimer's disease, Parkinson's
disease) IBD to DM and CVD, NAFLD, NASH Along with Various
Cancers Acta Scientific | February 2022
Curcumin has been evaluated for its biological actions:
Neuroinflammation; Alzheimer’s disease (AD); parkinson’s disease
(PD); antioxidant actions; other anti-inflammatory actions;
cardio protection; hepatoprotection in liver fibrosia; non
alcoholic fatty liver disease (NAFLD); non alcoholic
steatohepatitis (NASH); Anti cancer actions. We observed a total
of over 3000 articles and selected 53 articles for this
review with the journals constraints of up to 50 references.
Here we have reviewed in detail the mechanism of action of
Curcumin in various above mentioned diseases along with
transcription factors involved. Recently even in COVID its use
has got documented. In case of cancers, usually it is a good
coagent with other chemotherapeutic drugs, might hamper human
papilloma virus (HPV) infection as well as avoid cancer cervix
generation. In case of NASH, or liver cirrhosis its use with
beta blockers might aid in conversion back towards normalcy.
Curcumin's pleiotropic actions include inflammatory diseases
like cancer, CVD, arthritis, atherosclerosis, DM, gastric
disease, inflammatory bowel disease (IBD), psoriasis, HIV etc.
Curcumin is accepted to be a molecule having the capacity to
avoid/slowdown the pathological events resulting in age –
associated dementia, cognitive decrease, or depression.
Additionally, various evaluations have pointed that Curcumin is
a potential anticancer treatment in case of human papilloma
virus (HPV) infection, in addition to primary as well as
malignant squamous cell cancer.
Curcumin Alleviates Dextran Sulfate Sodium-induced
Colitis in Mice Through Regulating Gut Microbiota
Molecular Nutrition & Food Research | February 2022 Results
showed that oral administration with curcumin relieved
macroscopic pathological manifestations, e.g. colon length and
histological change. Moreover, it enhanced intestinal barrier
via increasing expression of tight junction proteins, e.g.
occludin, ZO-1, claudin-3; alleviated DSS-induced intestinal
apoptosis via suppressing caspase-3 pathway; mitigated
intestinal inflammation via inhibiting the MAPK/NFκB/STAT3
pathway. We also noticed that curcumin is beneficial for
modulating abundance of some specific bacteria, including
Akkermansia, Coprococcus, Roseburia, and Turicibacter, as well
as families such as F16, Enterococcaceae, and Aerococcaceae.
Most of the altered bacteria by curcumin are highly correlated
with colitis-associated parameters. Curcumin shows therapeutic
potential against colitis. It may be served as alternative
medicine or adjuvant therapy in the treatment of colitis.
Effectiveness
of Curcumin on Outcomes of Hospitalized COVID-19 Patients: A
Systematic Review of Clinical Trials
Nutrients | January 2022 The natural spice curcumin has
received recent attention in treating diseases involving
perturbations of the immune system and inflammation responses,
such as COVID-19. Curcumin and other curcuminoids are the main
bioactive ingredients of turmeric (Curcuma longa). They have
been used for millennia in the traditional medicines of multiple
cultures due to their anti-inflammatory, antioxidant,
antibacterial, antiviral, antidiabetic, and neuroprotective
properties. Curcuminoids have received approval from the USA
Food and Drug Administration (FDA), and these compounds have
good tolerability and safety. Furthermore, they have already
been tested with some successes in clinical trials targeting
various diseases. Curcumin treatment—as an adjunct therapy—helps
restore the balance between the pro-inflammatory and
anti-inflammatory pathways and, at the same time, reduces the
persistence of common COVID-19 symptoms and decreases mortality.
Together, these findings support curcumin formulations as
adjunctive therapy to reduce the hyper-inflammatory effect in
COVID-19 patients and improve patient outcomes. Curcumin
treatment led to the amelioration of cytokine storm
manifestation by reducing pro-inflammatory factors and
stimulating anti-inflammatory pathways. Thus, these findings
suggest that curcumin treatment may alleviate COVID-19 symptoms
by restoration of the pro-inflammatory and anti-inflammatory
balance. Furthermore, the study by Pawar et al. showed that
curcumin-piperine supplementation led to fewer thromboembolic
episodes following recovery from COVID-19 infections.
Cancer Chemoprevention: A Strategic Approach Using
Phytochemicals Frontiers in Pharmacology |
January 2022 Curcumin (diferuloylmethane), a polyphenol
isolated from Curcuma longa is the most studied phytochemical as
a chemopreventive. Curcumin displays a wide variety of
pharmacological functions such as anti-inflammatory agent,
anti-mutagenic agent, antineoplastic agent, hepatoprotective
agent, nutraceutical, anti-microbial agent, anti-oxidant agent,
and immunomodulator. It has been shown to have significant roles
in prevention, treatment and chemo sensitization of cancer cells
(Pavan et al., 2016). Studies have established the
anti-proliferative, anti-angiogenic, anti-metastatic, and
pro-apoptotic properties of curcumin (Anto et al., 2002;
Puliyappadamba et al., 2010; Bava et al., 2011; Vinod et al.,
2013). We have reported that curcumin exhibits potential
chemopreventive effect against nicotine-induced survival
signalling in lung cancer cells. We found that it down-regulates
multiple survival signals induced by nicotine in lung cancer
cells irrespective of their p53 status (Puliyappadamba et al.,
2010). Another study conducted in our laboratory revealed its
chemopreventive efficacy against the lung carcinogenesis induced
by B (a)P, a potential environmental carcinogen found in
cigarette smoke and deep-fried food, in Swiss albino mice (Puliyappadamba
et al., 2015). Curcumin treatment has a significant impact on
improving the general health of colorectal cancer patients by
enhancing expression of p53 molecules in tumour cells and also
by promoting the apoptosis of tumour cells (He et al., 2011;
Pricci et al., 2020). Curcumin intake causes the down-regulation
of NF-kB, COX-2 and phosphorylated STAT3 in peripheral blood
mononuclear cells from patients with pancreatic cancer (Dhillon
et al., 2008). It has been reported that, daily curcumin intake
leads to a significant and dose-dependent reduction in
spontaneous ovarian cancer incidence and tumor growth in Hen
ovarian cancer model indicating a significant role of curcumin
as a chemopreventive strategy for ovarian cancer (Sahin et al.,
2018). The administration of curcumin to paediatric patients
with relapsed brain tumours undergoing chemotherapy increased
their response compared with the controls (Wolff et al., 2012).
Inflammaging
and Brain: Curcumin and Its Beneficial Potential as Regulator of
Microglia Activation Molecules | January
2022 Curcumin is a natural compound with a polyphenolic
structure. This turmeric extract derives from the rhizome of the
Curcuma longa, a member of Zingiberaceae, and shows a wide range
of biological and pharmacological activities including
antioxidant, anti-inflammatory, antimicrobial, immunomodulatory,
and anti-tumor activity. Curcumin is a widely studied polyphenol
isolated from Curcuma longa with a variety of pharmacologic
properties. It is well-known for its healing properties and has
been extensively used in Asian medicine to treat a variety of
illness conditions. The number of studies that suggest
beneficial effects of curcumin on brain pathologies and
age-related diseases is increasing. Curcumin is able to inhibit
the formation of reactive-oxygen species and other
pro-inflammatory mediators that are believed to play a pivotal
role in many age-related diseases. Curcumin has been recently
proposed as a potential useful remedy against neurodegenerative
disorders and brain ageing. In light of this, our current review
aims to discuss the potential positive effects of Curcumin on
the possibility to control inflammaging emphasizing the possible
modulation of inflammaging processes in neurodegenerative
diseases. Curcumin as dietary phenolic compound should be
considered as a pharmacological support for longevity,
especially in neurodegenerative and neuroinflammatory diseases,
due to its activity via declining oxidative stress, modulating
signal transduction and gene expression. Curcumin, in fact, is
effective as an immune enhancer in modulating systemic
inflammation and brain pathologies through multiple
communication mechanisms and, for this reason, is hopefully a
particularly promising natural agent in counteracting the
damages of aging and neurodegenerative diseases. In this
respect, the possible interventions by curcumin on microglia
suggest the possibility of this natural product to mediate
regulation of microglia phenotypes and its functions and also to
control redox imbalance and neuroinflammation, thus suggesting a
possible use of curcumin as therapeutic agent in preventing and
managing major chronic inflammatory disorders typical of the
inflammaging process, including brain diseases such as
Alzheimer’s disease, Parkinson’s disease, and Multiple
Sclerosis. Hence, once again, attention is paid to the
modulatory potential of curcumin in its ability to mediate the
anti-inflammatory effects and consequently to positively
influence immunity and brain aging. Therefore, the use of
curcumin as an anti-inflammatory agent with inhibitory effects
on microglial transformation could be a valid and promising
approach for the treatment of neurodegenerative disorders.
Multiple lines of evidence show that the involvement of
microglial cells in brain neuroinflammation process typical of
aging may be a target for pharmacological interventions. The
anti-inflammatory activity of curcumin in microglia is
ascribable to the ability of this molecule to inhibit many
pro-inflammatory mediators by impeding inflammatory cascades and
heightening endogenous anti-inflammatory mediators where
curcumin may act as an immunomodulator. In line with what
emerges from this review, there is evidence that the combination
of standard protocols or new therapies with the use of
curcumin-based formulations could be a desirable approach in the
containment and treatment of the inflammaging process, including
that related to the brain.
The Multifaceted Actions of Curcumin in Obesity
Natural Products and Human Diseases | January 2022 Crcumin,
the active ingredient in turmeric, has attracted considerable
research interest in tracking down the possible effects in
protection against obesity and obesity-related comorbidities.
According to the existing literature, curcumin may regulate
lipid metabolism and suppress chronic inflammation interacting
with white adipose tissue, which plays a central role in the
complications associated with obesity. Curcumin also inhibits
the differentiation of adipocyte and improves antioxidant
properties. In the present review, we sought to deliberate the
possible effects of curcumin in downregulating obesity and
curtailing the adverse health effects of obesity.
Curcumin
and Weight Loss: Does It Work?
International Journal of Molecular Sciences | January 2022
Curcumin is a polyphenolic compound that represents the most
important curcuminoid isolated from the rhizome of the plants.
It is believed that curcumin possess subtle effects through
multiple mechanisms and biochemical targets, collectively
leading to substantial health benefits. This indicates that this
compound has potential for preventing (and, in the future,
treating) obesity. Curcumin has many properties, including
antioxidant. The role of antioxidants during the occurrence of
oxidative stress is important, which in turn may contribute to
the prevention or delay of the development of many diseases
(including civilizational) and their possible complications.
Therefore, naturally derived antioxidants such as curcumin are
of high clinical value. The anti-inflammatory effect of curcumin
is equally significant. Curcumin inhibits and regulates tissue
production and secretions of pro-inflammatory cytokine, such as
interleukins or tumor necrosis factor alpha (TNF-α). Curcumin is
a potential anti-cancer agent because of its multidirectional
properties with regard to the signaling/molecular pathways.
Curcumin possesses the ability to modulate the core pathways
involved in cancer cell proliferation, apoptosis, cell cycle
arrest, paraptosis, autophagy, oxidative stress and tumor cell
motility. Curcumin and Curcuma longa extract inhibit the growth
of microorganisms, both G(+) and G(-) bacteria, which often
cause human infectious diseases. Curcumin is known to have an
antiviral effect; it also has been suggested as a potential
treatment option for patients with COVID-19. Curcumin has an
anti-diabetic effect through, for example, enhancing glucose
uptake and improving pancreatic beta cell function. In addition,
curcumin contributes to the reduction of the gluconeogenesis
process and to the increase of glucokinase activity. Curcumin
was able to restore oxidative stress and DNA methyltransferase
functions against diabetic retinopathy. Moreover, curcumin has
shown anti-lipidemic effects. There are animal model studies on
the use of curcumin in pregnancy. Due to the anti-inflammatory
activity of this compound, the possibility of using this
compound in the treatment of complications of pregnancy has been
suggested, including Gestational Diabetes Mellitus, PreTerm
Birth, Preeclampsia and exposure to toxic agents and pathogens.
Other activities of curcumin worth mentioning include immune
modulation, cardiovascular protection, anti-pulmonary fibrosis,
anti-chronic obstructive pulmonary disease and anti-dementia
activity. There is a growing scientific interest in curcumin’s
therapeutic potential. Indeed, more and more clinical trials
based on curcumin administration have been published or are
underway. Curcumin is a promising natural bioactive compound
which possesses numerous pharmacological activities. It shows
multiple mechanism of action and can affect cellular biochemical
and physiological regulation. In pharmacies, there are more and
more preparations containing curcumin recommended for the
prevention of obesity.
Curcumin
alleviates restraint stress-induced learning and memory deficit
and activity Behavioral Neuroscience |
January 2022 Several investigations have reported that
curcumin has a protective effect against stress disturbance. The
present study is designed to investigate the effects of curcumin
on learning and memory, activity, biochemical, morphology
changes, and apoptosis in the hippocampus and prefrontal cortex
of restraint stress rats. Curcumin inhibited and reversed the
changes of stress induced in the prefrontal cortex and
hippocampus of the rats. These findings provided evidence for
the protective effect of curcumin therapy on biochemical,
morphology, and behavioral changes induced by restraint stress.
Curcumin
improves atherosclerosis by inhibiting the epigenetic repression
of lncRNA MIAT to miR-124 Vascular |
January 2022 Curcumin has protective effect on
atherosclerosis. Curcumin suppressed inflammation in
atherosclerosis mouse model and ox-LDL-induced cell model.
Curcumin relieved ox-LDL-induced cell inflammation. MIAT/miR-124
axis mediated the effect of curcumin on atherosclerosis and
altered cell apoptosis and proliferation, both in vivo and in
vitro. These data further support the application of curcumin in
control of atherosclerosis advancement.
Effect of curcumin supplementation on muscle damage,
antioxidant status and inflammatory factors after successive
simulated taekwondo competitions Science &
Sports | January 2022 Creatine kinase (CK), lactate
dehydrogenase (LDH) and Malondialdehyde (MDA) increased
significantly after the competition in placebo group compared to
Curcumin supplemented group. Total antioxidant capacity (TAC),
significantly increased in Curcumin supplemented compared to
placebo group after the competition. Based on the results of
this study, Curcumin supplementation has positive effects on
reducing muscle damage and oxidative stress.
Curcumin Induces Immunogenic Cell Death In Murine
Colorectal Carcinoma Pharmacological
Research | January 2022 Curcumin, a compound found in the
rhizome of Curcuma longa, is known to impair the function in
cancer cells. This event triggers apoptosis in curcumin-treated
cells and can be an important mechanism of the pharmacological
effects attributed to curcumin. The present work suggests that
curcumin is an inducer of immunogenic cell death. This
observation brings more insights into the mechanism of action of
curcumin. It has already been shown that the efficacy of certain
cancer therapies, such as anthracycline-based chemotherapy,
photodynamic therapy, and radiotherapy, also rely on their
ability to reinstate cancer immunosurveillance. Circumventing
the immune evasion strategies deployed by cancers and
reeducating the host immune system to detect and clear tumor
cells can be used as strategies to treat cancer. Thus, the use
of curcumin not only to directly kill cancer cells, but also to
help inducing an immune response against tumor antigens is an
alternative that can be explored in future studies.
Dietary
curcumin restores insulin homeostasis in diet-induced obese aged
mice Aging | January 2022 Curcumin is a
bioactive polyphenolic compound extracted from the herb
Curcuma longa. Curcumin treatment maintains insulin
homeostasis during aging and dietary challenge that is mediated
by hepatic IDE. It has antioxidant, anti-inflammatory, and
anti-diabetic properties which should mitigate age-associated
diseases. Curcumin supplementation suppresses body weight
gain and fat accumulation in aged mice. Its basic mechanism of
action as an anti-diabetic therapeutic agent was largely unknown
however we previously demonstrated that curcumin supplementation
increases insulin sensitivity in hepatocytes by upregulating
hepatic IDE expression and preserved islet integrity in a
diet-induced obese (DIO) mouse model. Curcumin changes hepatic
gene expression profiling and supplementation preserves
pancreatic islet integrity in aged mice. Furthermore, we
enumerated various cellular and molecular events in the insulin
signaling pathway regulated by curcumin. Dietary curcumin
alters gene expression associated with insulin signaling and
senescence pathways in the aged mice. In this study, we sought
to determine if curcumin supplementation during a nutrient
stressor known to cause insulin resistance in aged mice might be
beneficial to preserving hepatocytes in an insulin-sensitive
phenotype while protecting β -cells from the need to compensate
for insulin resistance. In summary, our study illustrates that
curcumin supplementation in aged individuals is likely to play a
role in mitigating reduced hepatic insulin sensitivity due to
aging per se and dietary challenges. It seems convincing that
curcumin positively regulates insulin sensitivity in hepatocytes
because of the upregulation of IDE that is reflected in reduced
demand for increased insulin secretion and synthesis. Thus,
curcumin is a potent, natural therapeutic agent which acts in a
multifaceted manner to protect aging-induced metabolic
disorders.
Nrf2-Related
Therapeutic Effects of Curcumin in Different Disorders
Biomolecules | January 2022 Curcumin is a
natural polyphenol with antioxidant, antibacterial, anti-cancer,
and anti-inflammation effects. This substance has been shown to
affect the activity of Nrf2 signaling, a pathway that is
activated in response to stress and decreases levels of reactive
oxygen species and electrophilic substances. Nrf2-related
effects of curcumin have been investigated in different
contexts, including gastrointestinal disorders,
ischemia-reperfusion injury, diabetes mellitus, nervous system
diseases, renal diseases, pulmonary diseases, cardiovascular
diseases as well as cancers. In the current review, we discuss
the Nrf2-mediated therapeutic effects of curcumin in these
conditions. The data reviewed in the current manuscript
indicates curcumin as a potential activator of Nrf2 and a
therapeutic substance for the protection of cells in several
pathological conditions.
Curcumin alters distinct molecular pathways in
breast cancer subtypes Cancer Reports |
January 2022 Curcumin is well known for its anticancer
properties. Its cytotoxic activity has been documented in
several cancer cell lines, including breast cancer. The
pleiotropic activity of curcumin as an antioxidant, an
antiangiogenic, antiproliferative, and pro-apoptotic, is due to
its diverse targets, such as signaling pathways, protein/enzyme,
or noncoding gene. Curcumin, a polyphenol extracted from
turmeric, is well known for its multifaceted properties like
anti-inflammatory, antioxidant, anti-bacterial, anti-malarial,
and anticancer. Clinical and preclinical studies have validated
the role of curcumin in varied human chronic diseases, including
cancer. The therapeutic potential of curcumin can be attributed
to its capability to regulate both epigenome and transcriptome.
In conclusion, curcumin regulates miRNA and mRNA in a cell type
specific manner. Curcumin altered different pathways in breast
cancer cell lines such as cell cycle, migration, invasion, and
so forth. The integrative analysis led to the detection of
miRNAs and mRNAs pairs, which can be used as biomarkers,
associated with carcinogenesis, diagnosis and treatment response
in breast cancer.
Curcumin exerts a protective effect against obesity
and liver injury induced by an atherogenic diet
Functional Foods in Health and Disease | January 2022
Background: Curcumin is a natural yellow polyphenol extracted
from the turmeric rhizome (Curcuma longa). Curcumin is
known for its potential therapeutic properties as an analgesic,
anti-inflammatory, antioxidant, antimicrobial, hepatoprotective,
and anti-mutagenic, although some of these biological activities
remain unproven. Epidemiological studies have shown a positive
relationship between high-fat diets and diet-related chronic
diseases. We hypothesized that some adverse effects of consuming
atherogenic or high-fat diets can be ameliorated by curcumin
supplementation. This study provides supporting evidence to
confirm the beneficial effects of curcumin from the point of
view of functional food science.
Age-related alterations to working memory and to
pyramidal neurons in the prefrontal cortex of rhesus monkeys
begin in early middle-age and are partially ameliorated by
dietary curcumin. Neurobiology of Aging |
January 2022 Curcumin-treated subjects exhibit better working
memory ability and less neuronal excitability. Middle-aged
subjects given curcumin exhibited better workng memory
performance and less neuronal excitability compared to control
subjects. These findings suggest that the appropriate time frame
for intervention for age-related cognitive changes is early
middle age, and points to the efficacy of curcumin in delaying
working memory decline.
Curcumin inhibits the invasion and metastasis of
triple negative breast cancer Journal of
Ethnopharmacology | January 2022 Modern pharmacological
studies have found that curcumin has many kinds of
pharmacological activities of anti-inflammatory, anti-tumor,
anti-angiogenesis, anti-metastasis and anti-multidrug
resistance. Curcumin has good anti-inflammatory (Lei et al.,
2014), anti-oxidation (Santosh et al., 2007), and reducing the
levels of ROS(Sethi et al., 2008). It can also inhibit the
activation of multiple pathways such as NF-κB (Cho et al., 2007)
and IL-1α, IL-6 and other gene expression (Momeni and Eskandari,
2017). A recent study showed that curcumin inhibited the
expression of HIF-1 by degrading ARNT in cancer stem-like cells,
thereby improving the hypoxia environment and promoting the
early apoptosis of breast cancer cells (Sarighieh et al.,2020).
Curcumin could significantly reduce cancer proliferation and the
expression level of PLAC8 in MCF-7/TAM cells through proteasome
and PLAC8/MAPK signaling pathways which showed that curcumin
might be a potential adjuvant therapeutic agent for the
treatment of tamoxifen-resistant patients (Mao et al.,2021).
Moreover, curcumin, as the main ingredient of curry, has no
obvious toxic and side effects according to toxicological
studies, so it has great potential in the treatment of breast
cancer (Lewis and Veltmaat, 2004). Our previous study found that
curcumin inhibited the proliferation of breast cancer cells
MDA-MB-231 and MCF-7 in vitro and growth of xenograft in vivo.
In this study, we found that Gli1 overexpression in MDA-MB-231
adherent cells could promote cell proliferation, invasion and
migration, which were inhibited after curcumin and GANT61
treatment. Moreover, curcumin inhibited the formation of
mammospheres, and down-regulated the expression of PTCH1,Gli1,
Gli2 in Hh pathway in adherent cells, and the expression of
E-cadherin, vimentin of EMT genes and Gli1,Gli2, SMO of Hh
pathway in MDA-MB-231 mammospheres. In addition, further studies
demonstrated that curcumin could inhibit the entry of Gli1 into
the nucleus. These data suggested curcumin may inhibit invasion
and metastasis of TN breast cancer cells by targeting Gli1.
Curcumin can inhibit the proliferation and metastasis of TN
breast cancercells, EMT and characteristics of breast cancer
stem cells.
Protective Effects of Curcumin in the Reproductive
System Natural Products and Human Diseases
| January 2022 The well-known antioxidant natural product
curcumin may have properties which could diminish toxic effects.
Curcumin has also shown some promise in the cryoprotection of
sperm samples through its antioxidant potential.
Curcumin supplementation in pediatric patients: A
systematic review of current clinical evidence
Phytotherapy Research | January 2022 Clinical efficacy and
safety of curcumin were assessed in children with inflammatory
and immune disorders (including asthma, inflammatory bowel
disease (IBD), and juvenile idiopathic arthritis (JIA)),
metabolic disorders, autosomal dominant polycystic kidney
disease (ADPKD), cystic fibrosis (CF), tetralogy of Fallot
(TOF), and infectious diseases. Curcumin was administered in a
wide range of doses (45 mg–4,000 mg daily) and durations
(2–48 weeks). Overall, curcumin was well tolerated in all
studies and improved the severity of inflammatory and immune
disorders and metabolic diseases. However, more studies are
needed to clarify the role of curcumin supplementation among
children with ADPKD, CF, TOF, and infectious diseases.
Curcumin Relieves Chronic Unpredictable Mild
Stress-Induced Depression-Like Behavior
Behavioral Neurology | January 2022 Curcumin, the major
active component extracted from the Chinese medicine Curcuma
longa, has been reported to possess neuroprotective effects.
Ccurcumin’s potential antidepressant-like effects have been
highlighted in many preclinical trials conducted on rats and
mice models of depression. Curcumin might be effective as
adjunctive treatment in depressive disorders, indicating the
promising efficacy of curcumin depression. More and more studies
have discussed the potential mechanism of curcumin's
antidepressant-like effects. Our previous study found that
curcumin could restore changes in proinflammatory cytokines and
the indolamine-2, 3-dioxygenase- (IDO-) kynurenine pathway in
the hippocampus of CUMS rats, which might ultimately contribute
to its antidepressant-like effect. Another study conducted by
our teammates Liao et al. suggested that the possible
antidepressant-like effects of curcumin are associated with
oxidative stress and with changes in the activation of
erythroid-2-related factor 2 (Nrf2) in the brain. Moreover, Liao
et al. found that curcumin could reverse the decreased
expression of BDNF. Other studies have also indicated curcumin’s
ability to increase BDNF levels. These studies point strongly to
an association between the antidepressant-like effects of
curcumin and the regulation of BDNF levels. Curcumin
successfully attenuated the abnormal behaviors induced by CUMS
and effectively prevented CUMS-induced reduction of PGC-1α,
ERRα, FNDC5, and BDNF expressions. Curcumin also enhanced PGC-1α
and ERRα translocation from cytoplasm to nucleus. Furthermore,
we found that curcumin supplementation effectively promoted
neurocyte proliferation and suppressed neuronal apoptosis
induced by CUMS. Of note, the PGC-1α inhibitor SR18292
remarkably reversed the beneficial effects of curcumin on
depressed rats, indicating an important role of PGC-1α in the
antidepressant-like effects of curcumin. Collectively, our data
evaluating the neuroprotective action of curcumin in the CUMS
rats highlights the involvement of the PGC-1α/FNDC5/BDNF pathway
in the antidepressant-like effects of curcumin.
Role of Curcumin in Retinal Diseases—A review
Clinical and Experimental Ophthalmology | January 2022
Curcumin showed its pleiotropic effects in retinal diseases like
diabetic retinopathy by increasing anti-oxidant enzymes,
upregulating HO-1, nrf2 and reducing or inhibiting inflammatory
mediators, growth factors and by inhibiting proliferation and
migration of retinal endothelial cells in a dose-dependent
manner in HRPC, HREC and ARPE-19 cells. In age-related macular
degeneration, curcumin acts by reducing ROS and inhibiting
apoptosis inducing proteins and cellular inflammatory genes and
upregulating HO-1, thioredoxin and NQO1. In retinitis pigmentosa,
curcumin has been shown to delay structural defects of P23H gene
in P23H-rhodopsin transgenic rats. In proliferative
vitreoretinopathy, curcumin inhibited the action of EGF in a
dose- and time-dependent manner. In retinal ischemia reperfusion
injury, curcumin downregulates IL-17, IL-23, NFKB, STAT-3, MCP-1
and JNK. In retinoblastoma, curcumin inhibits proliferation,
migration and apoptosis of RBY79 and SO-RB50. Curcumin has
already proven its efficacy in inhibiting viral replication,
coagulation and cytokine storm in COVID era. Curcumin is a
curcuminoid obtained from turmeric (curcuma longa) that belongs
to the Zingiberaceae family. They belong to the group of
phytocompounds that are biologically active molecules obtained
from plants with positive effects on health. Curcumin is a bis-α,β-unsaturated
β-diketone with the chemical name
1,7-bis-(4-hydroxy-3-methoxyphenyl)1,6-heptadiene-3,5-dione and
commonly called diferuloylmethane, E100 (European code of food
additives) or Natural Yellow 3. Its chemical formula is C21H20O6
and molecular weight is 368.38 gm/mol. It has two aromatic ring
systems containing o-methoxy phenolic groups that are linked
with a seven-carbon linker consisting of α, β-unsaturated
β-diketone moiety. It also exists in two tautomeric forms,
keto-enol and diketo tautomers. It is present in keto-enol form
in polar organic solvents, which is the predominant form of
tautomer. Cheng et al. studied the pharmacokinetics, toxicology
and biologically effective dose of curcumin in humans with high
risk or premalignant lesions. An initial dose of 500 mg once a
day in empty stomach in 25 patients and the dose was increased
to 1000, 2000, 4000, 8000 and 12,000 if there was no
toxicity ≥ grade 2 in at least 3 successive patients. No
toxicity was seen in doses up to 8000 mg. Curcumin showed no
toxicity up to 8000 mg when taken for 3 months.
Archived studies and
news on curcumin and turmeric 1984 - 2021
|
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How may Curcumin
effect aging and longevity as an antiaging agent? |
Effect of Curcumin
on Vascular Aging
| Growing evidence indicates curcumin as a promising
antiaging agent. The effects of curcumin feeding have been
largely investigated in animal models, unanimously reporting a
suppression of intermediated oxidative stress and inflammation.
By chelating nitrogen dioxide (NO2), curcumin administration in
mice significantly attenuates nitric oxide- (NO-) associated
vascular endothelial dysfunction and generation of advanced
glycation end-products (AGEs), leading determinants of
age-related large elastic artery stiffening. As an additional
mechanism, curcumin fixes lysosomal membranes and reduces the
function of lysosomal acid hydrolases, thus preventing the
aberrant deposition of different connective tissue components in
aging endothelium. curcumin mitigated hypertrophy in the aging heart
via suppression of p300, the global transcription activator.
Beneficial effects of curcumin on vascular aging also concern
the development of age-related macular degeneration (AMD), one
of the most important causes of blindness in elderly. Curcumin
remarkably increases the viability of retinal pigment epithelial
cells (RPECs) modulating their proliferation apoptosis and OS.
Overall, those evidences suggest potential application of
curcumin as an innovative approach to AMD, as for other ocular
diseases (e.g., ocular dryness, conjunctivitis, uveitis,
pterygium, and glaucoma). Even curcumin has been found to
prevent the development of cataract in diabetic rats by
decreasing AGE accumulation and serum LPO. Curcumin reverses
those effects in cultured ECs, whereas in experimental models,
prolonged curcumin feeding decreased ROS generation and promoted
cerebrovascular endothelium-dependent relaxation, finally
leading to improved cerebrovascular function. Neuroprotective
effects of curcumin due to UCP2 overexpression suppression
especially target hippocampal neurogenesis in the CA1 area, thus
affecting spatial learning and memory. Curcumin also prevents
detrimental effects of chronic cerebral hypoperfusion by
maintaining cholesterol homeostasis. Curcumin also contributes
to maintain cholesterol homeostasis, otherwise upset by chronic
cerebral ischemia. Indeed, curcumin promotes cholesterol efflux.
Effect of Curcumin on Longevity and Lifespan | Curcumin was
shown to increase the fecundity, reproductive lifespan, and
child viability of D. melanogaster. It has been shown
that curcumin supplementation of D. melanogaster
elevated the developmental duration and longevity of adult
Drosophila possibly through epigenetic programming of the
pace of life. Curcumin increased longevity was observed in two
distinctive strains of D. melanogaste as a result of the delayed
expression of aging genes, improved locomotion, and
chemoprevention as well. Curcumin was also shown to reduce OS,
DNA damage, and number of mutagenic phenotypes induced via
high-dose ionizing irradiation. Also, in vivo experiments on
curcumin -fed diets (0.5 and 1.0 mg/g of diet) were effective in
extending the average lifespan in both females (6.2% and 25.8%,
respectively) and males (15.5% and 12.6%, respectively). Also,
in C. elegans, curcumin effectively improves lifespan
and aging by lowering intracellular ROS and lipofuscin. The
effects of curcumin on C. elegans longevity are
manifested by body size and pharyngeal pumping rate. This
evidence indicates that curcumin would exert its effects
independently of the Age-1-DAF-16 pathway but rather through
other constituents of the IIS pathway. With regard to cognitive
impairment, the in vivo experiment demonstrated that curcumin
can improve learning and memory also reducing Aβ plaque
formation in the context of Alzheimer disease. D.
melanogaster is a promising animal model for research in
AD. By increasing amyloid fibril conversion, curcumin reduces
the generation of prefibrillar/oligomeric species of Aβ,
ultimately protecting against neurotoxicity. The human β-amyloid
precursor cleavage enzyme (BACE-1) is another critical enzyme
targeted by curcumin in the D. melanogaster model of
Alzheimer disease. Effect of Curcumin on Cell Senescence | The
antiaging effect of curcumin does not rely on delayed cellular
senescence. As reported by Banji et al., curcumin (40 mg/kg) and
piperine (12 mg/kg), especially when combined, counteract
D-gal-induced senescence in male Wistar rats by targeting OS and
lipofuscin deposition, finally leading to higher hippocampal
volume and function with improved spatial memory and
serotoninergic signaling. Another study even reported how
long-time curcumin therapy may progressively reverse cognitive
dysfunction in D-gal-induced senescent mice by delaying the
aging process and improving cognitive functions and locomotor
activity, as well as restoring the mitochondrial enzyme complex
function curcumin. In a recent study, curcumin supplementation
rejuvenates senescence-associated changes in thymus among
D-gal-induced senescent mice through promotion of proliferating
cells, preventing cells from apoptosis, and enhancing the
transcription of the autoimmune regulator. Curcumin feeding
(50 mg/kg) was also tested in senescence-accelerated mouse prone
mice resulting in increased hippocampal SOD activity as well as
upregulation of p-calcium/calmodulin-dependent kinase II.
Overall, these findings suggest a role of curcumin in improving
cognitive difficulties and the expression of hippocampal
plasticity-associated proteins. With regard to vascular
function, curcumin administration significantly mitigated
premature senescence in HUVECs, characterized by a reduction of
senescence-related β-galactosidase-positive cells, cell
division, levels of senescence-related protein p21 RNA, OS, and
apoptosis. Curcumin is also associated with enhanced eNOS
phosphorylation and NO generation, in addition to upregulating
Sirt1 transcription, translation, and enzymatic activity. In
light of these mechanisms, diets containing curcumin were
demonstrated to significantly extend mean lifespan in
male C57BL/6 mice and delayed the OS-caused premature
senescence. As recently demonstrated, Sirt1 signaling also
mediates the anti-inflammatory effects of curcumin in C57BL/6
mice fed with high fat diet in addition to improved myocardial
structure and function in streptozocin-induced diabetic mice fed
with THC (120 mg/kg/d). Even more recently, it has been
hypothesized that the antiaging effect of curcumin may rely on
the control of core clock genes. Curcumin treatment in middle
aged male Wistar rats restored the phase and daily pulse.
Moreover, it has been shown that curcumin mitigated mouse
ovarian aging, upgraded embryonic development, promoted oocyte
maturation and fertilization via improvement of ovarian
hormones, and elevated the amounts of SIRT1 and 3 genes as well
as attenuation of aging-associated oxidative stress and cell
death. Besides, curcumin can reduce oxidative stress,
inflammation status, and lipofuscin deposition in aged rat
liver. |
|
How may Curcumin work against Neurological and neurodegenerative
disorders such as Alzheimer's disease, Parkinson's disease,
Multiple Sclerosis, Huntington’s Disease, and cognitive decline
or impairment? |
Effect of Curcumin on Alzheimer's
Disease | Evidence has accumulated that curcumin has
neuroprotective properties and is a candidate for the treatment
of Alzheimer’s disease. In an Alzheimer’s disease transgenic
mouse, curcumin decreased oxidative stress and repaired amyloid
pathology. Antioxidant and anti-inflammatory features of
curcumin helped to minimize the manifestation of Alzheimer’s
disease, which is characterized by inflammation and oxidation.
Recent studies have indicated that curcumin treatment can
promote the decomposition of β-amyloid in brain tissues and
prevent the aberrant production and accumulation of β-amyloid,
which reduces the hyperphosphorylation of tau protein and
effectively prevents the degeneration and injury of brain
neurons. Curcumin has protective effects for several risk
factors of neurodegeneration and is used in the treatment of
Alzheimer's disease as well. In vivo studies show the beneficial
effects of curcumin on cognition with a dose-dependent manner
that higher dosages is more effective as compared to lower
dosages. Based on the preclinical findings, curcumin stabilizes/prevents cognitive decline in
Alzheimer's disease. A literature review was conducted to verify
studies that evaluated the effects of curcumin supplementation
on neurodegenerative / psychological disorders such as
Alzheimer's and depression in animal and human models, and their
respective mechanisms of action. Scholar google, ScienceDirect
and PubMed electronic databases were consulted up to September
2021. In the search, the following descriptor combinations were
used in the English-language databases: “BDNF”, “Neurogenesis”,
“Curcumin BDNF”, “Curcumin Bioavailability”, “Curcumin
Depression”, “Curcumin Depression BDNF”, “Curcumin Depression
Inflammation”, “Curcumin Serotonin Depression”, “Depression
BDNF”, “Depression Brain Size”, “Depression mechanism”,
“Depression Medication”, “Depression Neurogenesis”, “Polyphenol
Depression”, “Polyphenol Bioavailability”, “Alzheimer's”,
“Alzheimer's BDNF”, “Alzheimer's Curcumin”, “Curcumin
Alzheimer's BDNF”, “Alzheimer's Inflammation”, “Alzheimer's
Oxidation”, "Curcumin Tau protein", "Alzheimer Metals",
"Alzheimer Neurogenesis", "Exercise BDNF", "Calorie restriction
BDNF ”,“ Omega 3 BDNF ”. In their review, Pluta and colleagues focus on the role
and mechanisms of curcumin in inhibiting ischemia/reperfusion
brain injury and potential therapeutic strategies in the
treatment of ischemic brain damage of the Alzheimer’s disease
phenotype. Comparably, Ferreira and colleagues also delineate
neuroprotective characteristics by summarizing what is known
about the role of curcumin on transthyretin amyloidosis.
According to previous reports, curcumin modulates abnormal
transthyretin (TTR) aggregation and inhibits its deposition in
the tissue. As the gut–brain axis is linked to
neurodegeneration, curcumin exerts neuroprotective effect
against neurodegenerative disorders by restoring the intestinal
barrier function and a healthy gut microbiome. These findings
highlight the importance of neuroprotective effect of curcumin
against brain damage by regulating both inflammation and
oxidative stress. This is consistent with previous findings
where curcumin was shown to reduce significantly the mRNA
expression of NF-kB and TLR4 and showed protective effects
against glutamate neurotoxicity. Studies have shown that
curcumin has a therapeutic effect on Alzheimer’s disease by
several molecular mechanisms, including decreasing oxidative
damage and constraining the creation of the Aβ fibrils in vitro.
The anti-inflammation effects of curcumin as a food additive
were evaluated in the APPSw mice (Alzheimer-like model) at
several doses. The results have indicated that low-dose curcumin
(160 ppm) reduced GFAP, which is an astrocytic marker associated
with inflammatory processes. Furthermore, the effect of curcumin
on spatial memory (an Alzheimer’s disease symptom) in
Alzheimer’s disease rat models has shown that curcumin
significantly decreases GFAP mRNA in hippocampal astrocytes,
which improves the spatial memory in the Alzheimer’s disease rat
model. Ambegaokar et al. reported that the inhibition property
of curcumin is dose and time-dependent. For example, curcumin
concentrations of 15–30 μM are more effective for short trials
(<24 h), while its concentrations of 5–15 μM are better suited
for longer periods (4–6 days). These data suggest that curcumin
may be more effective in preventing AD in low doses if used for
long periods. Accumulating data show that Aβ can increase the
expression of COX-2, IL-1, and IL-6, while decreasing the
peroxisome proliferator-activated receptor-gamma (PPARγ) in
amyloid-beta protein precursor transgenic mice, and curcumin can
inhibit this function in amyloid-beta-treated astrocytes. Most
of the literature about curcumin indicates that this spice has
especially strong properties against AD. For instance, the
incidence of Alzheimer’s disease among Indian people (who
regularly consume these spices) is very low when compared with
the reported incidence in Western countries. Only 0.7% of 70–79
years old people in India are affected by AD; however, about
3.1% of Americans in this age range are also affected. Up to
now, the potential anti-amyloid therapeutic methods for
Alzheimer’s disease treatment have been focused on the amyloid
cascade theory, on which the use of Aβ vaccines and
metal-complexing agents is based. Strimpakos et al. reported
that curcumin has anti-amyloidogenic properties, thus acting
against AD-induced Aβ fibrils in vitro and improving cognitive
functioning in vivo. Interestingly, another study
analyzing the curcumin-mediated neuroprotective effects on brain
aging induced by d-galactose in in vitro and in vivo models
revealed an anti-aging effect through regulating neuronal loss,
apoptosis in D-galactose induced brain aging, and anti-oxidant
enzyme expression. Furthermore, curcumin improved neuronal
length and cellular senescence down-regulated expression of p16
and p21 and upregulated expression of antioxidant enzymes,
including SOD-1, GPX-1, and catalase. Administration of curcumin
ameliorated the cognitive impairment and suppressed apoptosis in
the cerebral cortex by downregulating Bax and poly (ADP-ribose)
polymerase expression and increasing Bcl-2 expression [86]. In
neurodegenerative diseases, such as AD, PD, ALS, microglia play
an important role by inducing oxidative stress, redox imbalance
and neuroinflammation. The activated microglia are represented
by M1 (pro-inflammatory) and M2 (anti-inflammatory) functional
phenotypes based on the surface molecules and cytokine
expression profiles. Different natural products show therapeutic
properties on microglia and consequent prevent neurodegenerative
diseases; they act by inhibition of microglia polarization and
production of inflammatory mediators. In microglia, curcumin
acts on different molecular targets. Curcumin inhibited
LPS-induced NF-kB and activator protein-1 (AP-1) DNA bindings in
BV2 microglial cells decreasing inflammatory mediators.
Peroxisome proliferation-activated receptor-γ (PPARγ) is a
transcription factor and nuclear receptor protein that regulates
inflammatory responses in microglia, astrocytes and when is
activated, PPARγ suppresses the production of proinflammatory
cytokines and inflammatory pathways by binding the peroxisome
proliferator response element. Curcumin activates PPARγ
which reduces NF-κB cytokine production in a mouse model of AD,
in rat hippocampal primary cell lines and primary astrocytes.
Moreover, our group has found that curcumin suppresses LPS
induced inflammatory response in microglia cells by down
regulation of PI3K/Akt and JAK/STAT/SOCS signaling pathway. In
addition, curcumin induces anti-inflammatory mediators, such as
HO-1/NRF-2 consequently reducing oxidative stress and
neuroinflammation. Curcumin treatment improved neuron loss and
degeneration, while also inhibited cellular senescence and
oxidative stress by upregulating antioxidant enzyme expression
in RA-induced SY5Y cells. In line with the findings described
above, the protective effect of curcumin against cognitive
impairment has been demonstrated in diabetes mellitus/chronical
cerebral hyperperfusion-induced cognitive deficit model.
Moreover, curcumin treatment attenuated the neuronal death and
suppressed neuroinflammation induced by microglial activation.
These protective effects involved the modulation of triggering
receptor expressed on myeloid cells 2 (TREM2)/TLR4/NF-kB
pathway. Curcumin treatment reduced nod-like receptor protein 3
(NLRP3) dependent pyroptosis. Since NLRP3-dependent pyroptosis
has been reported to be involved in the progression of
neurodegenerative diseases, this result suggests that curcumin
may be useful as pharmacological strategy for neurodegenerative
diseases. Further studies are needed for better understanding of
curcumin’s promising effects in preventing the neuronal loss and
cognition-decline related to aging. The pleiotropic activities of curcumin provide
multiple ways to tackle TTR pathophysiology, through direct
interaction of curcumin with TTR, or indirect effects affecting
signaling pathways associated with TTR amyloid fibril formation
and clearance. Bielak-Zmijewska and coworkers summarize
scientific data on curcumin’s ability to postpone progression of
age-related diseases in which cellular senescence is directly
involved. They furthermore point out that curcumin causes
elongation of the lifespan of model organisms and alleviates
aging symptoms. In addition, they discuss thoroughly curcumin’s
ability to modulate cellular senescence. Common brain disorders, including depression and Alzheimer’s disease, have
been linked to diminished levels of an important neurologic growth hormone
called brain-derived neurotrophic factor. Reports suggest Curcumin has
neuroprotective action in Alzheimer’s disease, major depression,
epilepsy, and other neurodegenerative disorders. The hippocampus
region of brain is associated with memory and cognition. Studies
have shown that hippocampus undergoes structural and biochemical
changes with normal aging that results in age-related
deterioration in hippocampus-dependent cognition. Curcumin has
been found to ameliorate age-related memory deficits in aged
mice. In elderly, regular curcumin intake improves cognitive
function and ameliorates age-related spatial memory deficits. An
Australian study, in the
Journal of Psychopharmacology in 2015,
found that curcumin improved attention and working memory and reduced mental
fatigue in older people who took it for four weeks, compared to a placebo. Several studies have shown that
curcumin, the active medicinal compound in turmeric, can increase levels of
BDNF in the human brain and therefore delay or even reverse a range of
common neurological disorders. One of the main drivers of this process is
brain-derived neurotrophic factor (BDNF), which is a type of
growth hormone that functions in your brain (20). Many common
brain disorders have been linked to decreased levels of this
hormone, including depression and Alzheimer's disease.
Interestingly, curcumin can increase brain levels of BDNF. By
doing this, it may be effective in delaying or even reversing
many brain diseases and age-related decreases in brain function.
It may also improve memory and make you smarter, which seems
logical given its effects on BDNF levels. However, controlled
studies in people are needed to confirm this. In addition, scientists are beginning to
suspect that the neurologic powers of curcumin don’t just stop there, with
research suggesting that this compound may improve memory and increase
cognitive capacity. Curcumin, thanks to its wide range of effects,
seems to help the brain resist buildup of harmful plaque in brains with
Alzheimer's. A
study in
the Annals of Indian Academy of Neurology explored curcumin's potential
for use in the treatment for Alzheimer's disease. Some of the key points
included: Curcumin may help the macrophages, which play an important role in
our immune system, clear the amyloid plaques found in Alzheimer's disease.
Curcumin has anti-proliferative actions on microglia. Microglia are immune
cells of the central nervous system that become active in response to any
number of stressors on the body. However, if the microglia have been
stimulated to react too often, they become hyper-reactive, which can trigger
system-wide inflammation that can be difficult to stop. Curcumin has
powerful antioxidant and anti-inflammatory properties. "Overall, curcumin
decreases the main chemical for inflammation and the transcription of
inflammatory cytokines …The exposure to curcumin also impaired the
production of pro-inflammatory cytokines (IL-1, IL-6 and TNF-)." As chronic
neuro-inflammation is considered one of the major factors in the development
of Alzheimer's, it's possible too that curcumin may help in the treatment of
other inflammatory disorders. Researchers found that Curcumin
not only reduces oxidative damage and inflammation, but also
reduces amyloid accumulation and synaptic marker loss and promotes amyloid
phagocytosis and clearance. Curcumin worked to prevent synaptic marker and
cognitive deficits caused by amyloid peptide infusion and abeta oligomer
toxicity in vitro, and may help the immune system clear the
brain of amyloid beta, which forms the plaques found in Alzheimer's disease. Clinical trials are in progress at UCLA with Curcumin
for Alzheimer's. In the
Alzheimer’s Disease Anti-Inflammatory Prevention Trial, researched showed that
reducing inflammation has positive effects on patients with Alzheimer’s.
Curcumin significantly lowered several inflammation markers, in addition to
reducing plaque on the brain (a sign of Alzheimer’s) by 43 to 50 percent.
The effect of curcumin (turmeric) on Alzheimer's disease: An overview
Neuroprotective activity has also been shown in curcumin. In Alzheimer’s
disease (AD), a peptide called β-amyloid (Aβ peptide) aggregates into
oligomers and fibrils and forms deposits known as amyloid (or senile)
plaques outside neurons in the hippocampus and cerebral cortex of patients.
Another feature of AD is the accumulation of intracellular neurofibrillary
tangles formed by phosphorylated Tau protein. Abnormal microglial
activation, oxidative stress, and neuronal death are also associated with
the progression of the disease. Curcumin has been found to inhibit Aβ fibril
formation and extension and to destabilize preformed fibrils in vitro. Metal chelation by curcumin might interfere with metal ion
(Cu2+/Zn2+)-induced Aβ aggregation. Curcumin might also affect the
trafficking of Aβ peptide precursor (APP) and the generation of Aβ peptides
from APP. Abnormally activated microglia and hypertrophic astrocytes around
amyloid plaques in AD brains release cytotoxic molecules, such as
proinflammatory cytokines and ROS, which enhance Aβ formation and deposition
and further damage neurons. Curcumin was found to reduce the inflammatory
response triggered by Aβ peptide-induced microglial activation and increase
neuronal cell survival. When injected into the carotid artery of a
transgenic mouse model of AD, curcumin was found to cross the blood-brain
barrier, bind to amyloid plaques, and block the formation of Aβ oligomers
and fibrils. In other animal models of AD, dietary curcumin decreased
biomarkers of inflammation and oxidative damage, increased Aβ peptide
clearance by macrophages, dismantled amyloid plaques in the brain,
stimulated neuronal cell growth in the hippocampus, and improved Aβ-induced
memory deficits. As a result of promising findings in animal models. a few
recent clinical trials have examined the effect of oral curcumin
supplementation on cognition in healthy older adults and AD patients. A significant reduction in mental
fatigue and higher levels of calmness and contentedness following cognitive
test sessions were observed in individuals who consumed curcumin (either
acutely or chronically) compared to the placebo group. Additionally, the
results of cognitive ability tests suggested that curcumin treatment had
limited benefits on cognitive function, as shown by better scores in
measures of sustained attention and working memory compared to placebo. The
results of a six-month trial in 27 patients with AD found that oral
supplementation with up to 4 g/day of curcumin - containing all three major
curcuminoids - was safe. Curcumin also helps inhibit
plaque that research has linked to neuron damage in the brain
and a sign of the disease. There may be good news on the horizon
because curcumin has been shown to cross the blood-brain
barrier. It’s known that inflammation and oxidative damage play
a role in Alzheimer's disease, and curcumin has beneficial
effects on both. In addition, a key feature of Alzheimer's
disease is a buildup of protein tangles called amyloid plaques.
Studies show that curcumin can help clear these plaques.
Alzheimer’s disease (AD) is a chronic neurodegenerative disease
characterized by the presence of hyperphosphorylated tau protein
in neurofibrillary tangles, selective neuronal loss, progressive
memory and cognitive impairment (Campbell and Gowran 2007). The
molecular pathogenesis of AD involves extracellular deposition
of beta-amyloid (Ab) peptides in the hippocampus and curcumin
is known to reduce Alzheimer’s pathology (Serafini et al. 2017)
possibly due to its anti-aggregatory properties (Cole, Teter,
and Frautschy 2007). In a clinical study, curcumin
administration (1 or 4 g, 6 months trial) significantly
increased the levels of antioxidant vitamin E without inducing
any adverse events in patients with AD (Baum et al. 2008). In
preclinical studies, curcumin is known to reduce Aboligomer and
fibril formation (Yang et al. 2005; Xiong et al. 2011), inhibit
the neurotoxicity of Abin the brain (Jiang et al. 2012; Sun,
Zhao, and Hu 2013), suppress Ab-induced inflammation (Lim et al.
2001; Lu et al. 2014) and markedly reduce the levels of IL-
1b(Griffin et al. 2006) and inducible nitric oxide synthase
(iNOS) (Begum et al. 2008) in transgenic mouse brain. Several
studies demonstrated dose-dependent neuroprotective effect of
curcumin against Ab-induced toxicity. Curcumin exhibited
anti-aggregatory effect against Ab plaque formation by metal
chelation (Huang et al. 2004; Tamagno et al. 2005), anti-oxidant
effects (Hamaguchi et al. 2009), cholesterol lowering effects
(Fassbender et al. 2001; Refolo et al. 2001), inhibition of
presenilin-2 and/or by increasing degrading enzymes such as
insulin-degrading enzyme and neprilysin (Wang et al. 2014).
Curcumin potentiate heat shock proteins production in response
to cellular stress, which protects neuronal cells from Ab
neurotoxicity and prevent Ab aggregation and accumulation
(Scapagnini et al. 2006; Ohtsuka and Suzuki 2000; Cummings et
al. 2001). Effect of Curcumin on Parkinson’s Disease |
Dietary curcumin is an important candidate in the prevention or
treatment of Parkinson’s disease.
Curcumin is suggested to be an effective therapeutic and
nutraceutical agent for Parkinson’s diseasetreatment.
Interestingly, curcumin was found to inhibit the synthesis of
MOA-B enzyme (Khatri and Juvekar, 2016), which would lead to an
increase in the level and availability of DA in the brain.
Neuroprotective effects of curcumin in a 6-hydroxydopmin e
animal model of Parkinson’s disease (El Nebrisi et al., 2020)
indicated an increase in the survival of striatal TH fibers and
SNpc neurons, decreased abnormal turning behavior, and exerted
neuroprotective properties. These findings provide evidence that
α7-nicotinic acetylcholine receptors could be a potential
therapeutic target and curcumin would be the first natural
source that is found to modulate nicotinic receptors in
Parkinson’s disease. Recent evidence indicates
decreased superoxide dismutase 1 (SOD1) expression in reactive
astrocytes in the damaged substantia nigra, thus leading to
inflammation and oxidative stress that contribute to the
degeneration of dopaminergic neurons in Parkinson’s disease.
Curcumin, through the preservation of SOD1 expression in
reactive striatal astrocytes in hemiparkinsonian mice, has
anti-inflammatory properties. Gui et al. showed that curcumin,
through the inhibition of CYP2E1 (the cytochrome P450 2E1)
expression and its activity in reducing ROS and maleic
dialdehyde in astrocytes, leads to protection of the
mesencephalic astrocytes against LPS-induced toxicities. These
results indicate that curcumin could affect the metabolism of
several compounds in the CNS and provide evidence for the
therapeutic approach in Parkinson’s disease using curcumin at
low concentration. Studies show that the oral administration of
curcumin (150 mg/kg/day for a week) in mouse models of
Parkinson’s disease reversed GFAP and inducible nitric oxide
synthase protein expression and also decreased proinflammatory
cytokine in the striatum, suggesting that curcumin can improve
motor performance in a mouse model of Parkinson’s disease. In
addition, curcumin, through the Bcl-2-mitochondria-ROS-inducible
nitric oxide synthase pathway, can protect against MPP+
(1-methyl-4-phenylpyridinium)- and MPTP−
(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced
apoptosis in PC12 cells. Curcumin can significantly inhibit
NF-κβ translocation and activation in astrocytes. In one study, chronic curcumin administration (50,
100 or 200 mg/kg, p.o., for 3 weeks) significantly ameliorated
behavioral alterations like locomotor activity and
motor-coordination in mouse model of Parkinson’s disease. In the
similar study, curcumin administration reduced oxidative damage
and mitochondrial dysfunction in brain homogenate by reducing
AChE activity. Curcumin administration decreased malondialdehyde
(MDA) and nitrite while increased superoxide dismutase (SOD),
catalase (CAT) and reduced glutathione (GSH) levels in the brain
homogenate of rotenone induced mouse model of Parkinson’s
disease (Khatri and Juvekar 2016). It has been demonstrated that
curcumin administration alleviate motor dysfunction and increase
tyrosine hydroxylase activity in rotenone induced Parkinson’s
disease rat model. Curcumin administration phosphorylates Nrf-2
and Akt thereby attenuated oxidative damage of dopaminergic
neuron (Cui, Li, and Zhu 2016). Moreover, dietary curcumin
supplementation 0.5% or 2.0% (w/w) attenuated
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced
neurotoxicity in mice via increasing the expression of glial
cell line-derived neurotrophic factor and TGF-b1 in
nigrostriatal dopaminergic system and thus slowing the
progression of Parkinson’s disease (He et al. 2015b). Curcumin
administration increased monoaminergic neurotransmitters such as
norepinephrine and dopamine in hippocampal homogenate and
alleviated hippocampal damage in 6-hydroxydopamine induced
Parkinson’s disease in rat. In addition, curcumin treatment
upregulated the expression of BDNF, TrkB and PI3K in the
hippocampus (Yang et al. 2014). Curcumin treatment (200 mg/kg,
for 1 week) significantly attenuated loss of tyrosine
hydroxylase, sustained SOD1 level and diminished activation of
microglia and astrocytes in the striatum. Effect of
Curcumin on Cognitive
Impairment | Curcumin has been reported to improve
neuropsychological functions. curcumin has several inhibitory
effects on combining aging and Alzheimer’s disease
pathophysiology, such as the suppression of amyloid precursor
protein (APP) and Aβ synthesis and the overexpression of ApoE
and Nrf2 gene, as well as the prohibition of p-mTOR and p-NF-κB.
Curcumin prevents D-gal-induced brain aging and cognitive
impairment through increments of antioxidant enzymes and
inhibition of apoptosis. Beneficial effects of curcumin on
mental abilities and functional capacities are associated with a
LPO reduction in brain tissue, especially in the hippocampal
area. Curcumin improves the redox state in this area and
prevents the decline of hippocampal long-term potentiation by
maintaining synapse input specificity. Recently, Olesen et al.
described that the dysfunction of synaptic mitochondria of the
hippocampus causing memory loss during aging. They showed that
curcumin feeding significantly improved integration and activity
of the synaptic mitochondrial of the hippocampus, inhibiting
mitochondrial swelling and enhancing the production of synapses
surrounding the mitochondria in mice. Effect of
Curcumin on Multiple Sclerosis and Amyotrophic Lateral Sclerosis
| Curcumin was studied to determine if it could help ALS
patients, particularly those with bulbar involvement, survive
longer (Ahmadi et al., 2018). Curcumin therapy reduced the
development of ALS and oxidative damage in a double-blind
therapeutic trial (Chico et al., 2018). Recent studies suggest that curcumin, through reduced MMP-9
enzyme activity and decreased release of IL-6 in the astrocyte
population of CNS, might beneficially cause anti-inflammatory
responses in neurodegenerative diseases, such as multiple
sclerosis. Curcumin represents some potential for treatments of
various autoimmune diseases related to Th17 cells including MS.
Curcumin, through interfering with protein kinase C activity and
Ca2+ entry, can eliminate both PMA and thapsigargin-induced ROS
generation by the dose-dependent manner. Curcumin can prevent
the production of H2O2 and NO; the free radicals produced by
macrophages and astrocytes in vitro. In EAE, curcumin has
important roles in lymphocyte proliferation inhibition,
reductions of IL-17 production by Th17 cells, and Toll-like
receptors 4 and 9 (TLR 4 and 9) downregulations. Xie et al.
reported that in EAE mice or rats, curcumin shrinks inflammatory
cells, including Th17 cells, and hinders its infiltration and
differentiation in the CNS. Curcumin has the promising potential
for treating multiple sclerosis. Curcumin delivering to the
animal models through intraperitoneal injection or oral
administration leads to NF-κβ pathway activation decreasing in
rat and mouse microglial cell cultures and also in the rat
brain. Furthermore, curcumin can also reduce NF-κβ activation in
human cell lines and can neutralize ROS in vitro and can
stimulate the Nrf2-ARE pathway similarly in the brain and
skeletal muscles of mice and also in isolated rat astrocytes.
SOD1-misfolded and -aggregated proteins in the motor neurons
have an important role in disease pathogenesis, and its
targeting treatment can decrease ALS progression in animal
models. As previously shown, curcumin can constrain SOD1
aggregation in vitro. Curcumin through gene expression can also
stimulate the clearance of the aggregated protein in PALS and
Alzheimer’s disease blood cells. Up to the present time, several
studies confirm that regimens’ treatment can cause motor neuron
enhancement (although there are several different descriptions
for these improvements). Furthermore, a small pilot trial
revealed some advantage of curcumin in PALS. Effect
of Curcumin on Huntington’s Disease | Studies using
established yeast models showed that curcumin inhibits mHTT
aggregation, by acting through endosome-sorting complexes
required for transport machinery and also destabilizes preformed
aggregates. Curcumin, by downregulation of Vps36, a component of
the endosome-sorting complexes required for transport-II
complex, prevents recruitment of misfolded protein to the
perivascular compartment, thus inhibiting the formation of large
aggregates. The amyloid-binding ability and anti-amyloid
properties of curcumin, along with its ease of oral
administration, make it an attractive therapeutic candidate for
several neurodegenerative diseases. |
|
How may Curcumin work against diabetes? |
Because of its anti-inflammatory
property, curcumin represents a promising therapeutic option for
Type 2 Diabetes. Curcuminoids have been demonstrated in diabetes
mellitus type 2 patients to improve insulin resistance, reduce
glucose and insulin levels, enhance adiponectin secretion, and
lower levels of leptin, resistin, interleukin (IL-6, IL-1β), and
TNF-α (Hajavi et al., 2017). Curcumin and its three
derivatives (dimethoxy curcumin, bisdemethoxycurcumin, and
diacetyl curcumin) were reported for their antioxidant
capabilities (Faizal et al., 2009). Curcumin’s ability to decrease blood sugar
levels in human patients was first reported in 1972. A male
patient who had diabetes for 16 years ingested 5 g of curcumin
over a period, after which his fasting blood sugar decreased
from 140 to 70 mg/dl. Ingestion of curcumin along with insulin
synergistically reduced the blood sugar level. Furthermore, when
the insulin dosage was decreased to the minimum, the
anti-diabetic effect of curcumin was persistent. Interestingly,
when the ingestion of curcumin and turmeric was discontinued for
a week, random blood sugar levels increased to 140 mg/dl.
Therefore, ingestion of a daily 5-g dose of curcumin was
resumed, which promptly reduced the fasting blood sugar level to
110 mg/dl. Blood urea in this patient after 3 months of turmeric
therapy was 20 to 22, and the patient’s electrocardiogram was
normal. Turmeric therapy was not associated with any palpable
adverse effects; rather, the beneficial effects of turmeric as a
good appetite stimulant and effective laxative were observed.
More recently, a randomized, double-blind, placebo-controlled
clinical trial assessed the efficacy of curcumin in delaying
development of Type 2 Diabetes in the prediabetes population.
After 9 months of treatment, 16.4% of participants in the
placebo group were diagnosed with Type 2 Diabetes, whereas
none were diagnosed with Type 2 Diabetes in the
curcumin-treated group (Fig. 6a). In addition, the participants
of curcumin-treated group showed a better overall function of β
cells, with higher HOMA-β and lower C-peptide levels. The
curcumin-treated participants also exhibited a lower level of
HOMA-IR and higher adiponectin when compared with the placebo
group. The authors of this study concluded that the curcumin may
be beneficial in a prediabetes population.
Curcumin has been shown to equal in effectiveness to the drug metformin
in the management of diabetes, but without negative side effects. In the
study curcumin was shown to lower blood glucose levels and reverse insulin
resistance by suppressing glucose production in the liver. Among those
verging on type 2 diabetes, curcumin capsules
seem to help stall the onset of the disease. The study that returned
these results found that while a little more than 16% of people taking a
placebo wound up with a diabetes diagnosis, no one taking curcumin received
one. A
clinical trial from Thailand, published in
Diabetes Care in
2012, found that people with prediabetes who took curcumin for nine months
had improved function of insulin-producing cells in the pancreas, along with
a significantly reduced risk of developing type 2 diabetes. Other studies
suggest that curcumin can improve insulin sensitivity. Another study found curcumin
improved metabolic
function and reduced the risk of plaque buildup in the arteries of
type-2 diabetes patients. Curcumin also acts as an anti-diabetic and
antioxidant in patients with
type-1 diabetes. Curcumin acts directly on liver cells to help
prevent them from becoming fatty, and studies have concluded that Curcumin may
have an anti-diabetic effect by decreasing serum fatty acid through the
promotion of fatty acid oxidation and utilization. Curcumin also works directly on pancreatic beta cells
to help them produce insulin normally. By helping the liver and the pancreas,
Curcumin is taking stress off the two most important organs whose function
declines before the onset of type 2 diabetes. Curcumin also influences key
hormones, supports major body organs, and regulates inflammatory signaling all
in ways that help correct or prevent metabolic problems. Curcumin helps lower
inappropriately high levels of leptin (reducing leptin resistance) while
boosting the all-important levels of the adiponectin
(which lowers insulin resistance). Curcumin also helps activate the fat-burning
gene signal PPAR gamma, which also helps to make more new, metabolically-fit fat
cells. Curcumin directly reduces major inflammatory events from occurring inside
white adipose tissue (tumor necrosis factor alpha, interleukin-6, and monocyte
chemotactic protein-1). By lowering such inflammation, the source of
overweight-induced disease is targeted. Oxidative stress and inflammation have
been implicated in the pathogenesis of type 2 diabetes mellitus
and related vascular complications. A large body of preclinical
evidence suggests that the antioxidant, anti-inflammatory, and
glucose-lowering activities of curcumin and its analogs may be
useful in the prevention and/or treatment of type 2 diabetes. In
a nine-month, randomized, double-blind, placebo-controlled study
in 237 subjects with impaired glucose tolerance (pre-diabetes),
no progression to overt diabetes was reported with a daily
ingestion of a mixture of curcuminoids (0.5 g), while 16.4% of
placebo-treated participants developed diabetes. In addition,
curcumin supplementation was shown to reduce insulin resistance
and improve measures of pancreatic β-cell function and glucose
tolerance. Supplemental curcumin was found to be as effective as
lipid-lowering drug atorvastatin (10 mg/day) in reducing
circulating markers of oxidative stress (malondialdehyde) and
inflammation (endothelin-1, TNFα, IL-6) and in improving
endothelial function. Another randomized controlled trial also
reported that oral curcumin supplementation (1.5 g/day) for six
months improved endothelial function, insulin sensitivity, and
metabolic markers associated with atherogenesis (plasma
triglycerides, visceral fat, total body fat) in participants
with type 2 diabetes. Finally, in a two-month randomized,
double-blind, placebo-controlled study in 40 individuals with
type 2 diabetic nephropathy (kidney disease), daily curcumin
ingestion (66.3 mg) significantly reduced urinary concentrations
of proteins and inflammation markers (TGF-β, IL-8), suggesting
that curcumin might be helpful with slowing the progression of
kidney damage and preventing kidney failure. The research on
curcumin suggests it can work as a hypoglycemic agent—lowering
and helping control blood glucose (blood sugar) levels in people
with type 2 diabetes. This can ultimately prevent those with the
disease from developing other serious health complications
associated with diabetes, such as neuropathy (damage to the
nervous system) and nephropathy (kidney disease). A study
published in the journal Biochemistry and Biophysical Research
Community explored how curcumin might be valuable in treating
diabetes, finding that it activates AMPK (which increases
glucose uptake) and suppresses gluconeogenic gene expression
(which suppresses glucose production in the liver) in hepatoma
cells. Interestingly, they found curcumin to be 500 times to
100,000 times (in the form known as tetrahydrocurcuminoids(THC))
more potent than metformin in activating AMPK and its downstream
target acetyl-CoA carboxylase. Diabetic neuropathy is a type of
neuronal damage, associated with chronic diabetes, characterized
by demyelination and deterioration of nerve fibers, alterations
in the micro- vasculature and loss of sensory fibers that leads
to pain, foot ulcers, amputations, depression, phobias,
anorexia, loss of memory and reduction in complex reasoning
skills (Patel and Udayabanu 2013). |
Curcumin
treatment (50 mg/kg, for 8 weeks) upregulated BDNF in frontal
cortex and hippocampus alongside reduced oxidative damage in the
hippocampus of diabetic db/db mice (Franco-Robles et al. 2014).
Curcumin administration significantly increased Na (þ) -K (þ)
-ATP activity, reduced lactate dehydrogenase (LDH) activity and
lactic acid content as well as stimulates Ca (þ) -Mg (þ) -ATP
activity in brain homogenate of alloxan induced diabetic mice.
In addition, curcumin administration ameliorated energy
metabolism in the brain homogenate of diabetic mice (Miao,
Cheng, and Li 2015). Curcumin administration (60 mg/kg, p.o.,
for two weeks) downregulated the expression of glucose
transporter (GLUT) type 3, muscarinic receptor type 3,
a7-nicotinic receptor and AChE in brain- stem and cortex of
streptozotocin induced diabetic rats. In addition, it reduced
the expression level of insulin receptor and choline
acetyltransferase in brainstem. Curcumin treatment upregulated
the gene expression of choline acetyltransferase, SOD and
insulin receptor in cortex. It is known to upregulate the
expression level of muscarinic cholinergic receptor 1 in
brainstem and cerebral cortex (Kumar et al. 2013) as well as
attenuate cognitive deficits in streptozotocin induced diabetic
rats (Kumar et al. 2011). Curcumin treatment (60 mg/kg, p.o.,
for 15 days) downregulated the expression level of dopaminergic
D1 and D2 receptor in the cortex. In addition, curcumin
administration significantly upregulated dopaminergic D1
receptor and downregulated D2 receptor in the cerebellum of
diabetic rodents. Curcumin treatment upregulated phospholipase C
and transcription factor cAMP response element-binding protein
expression in the cerebellum and cortex of streptozotocin
induced diabetic rats resulting in amelioration of emotional
and cognitive performance (Kumar et al. 2010). Curcumin
administration (60 mg/kg, p.o., for 16 days) upregulated the
glutamate decarboxylase while downregulated Bax, caspase 3 and
caspase 8 expressions in the cerebral cortex. In addition,
curcumin administration attenuated NMDA and AMPA receptor
mediated oxidative stress and excitotoxicity in the cerebral
cortex of streptozotocin induced diabetic rats (Jayanarayanan et
al. 2013). Curcumin supplemented (0.5%) with animal’s diet
decreased b-d-glucuronidase activity (Chougala et al. 2012),
nitric oxide level, total oxidant status, MDA level and
oxidative stress index. Diabetes mellitus, commonly referred to
as diabetes, is a chronic metabolic disorder characterized by
hyperglycemia, glycosuria, negative nitrogen balance, polydipsia
and sometimes ketonemia. In a randomized, double-blind,
placebo-controlled trial, oral curcumin extract supplementation
(three capsules per day, each curcumin capsule has curcuminoid
content of 250 mg) for nine months ameliorated b-cell function,
lowered C-peptide and increased homeostasis model assessment-b,
reduced insulin resistance and increased the adiponectin level
in type 2 diabetic subjects as compared to placebo group
(Chuengsamarn et al. 2012). In another clinical study, curcumin
administration lowered the level of HbA1c and fasting blood
glucose as well as partially reduced LDL-cholesterol and body
mass index in diabetic subjects (Rahimi et al. 2016). A recent
meta-analysis revealed that, curcumin or combined curcuminoids
supplementation effectively lowered the level of fasting blood
glucose in individuals with some degree of dysglycemia. In
addition, isolated curcumin supplementation significantly
decreased HbA1c as compared to placebo and suggested its
beneficial role as adjuvant in the treatment of dysglycemic
patients (de Melo, Dos Santos, and Bueno 2018). In animal study,
curcumin administration is reported to reduce glucose
intolerance through induction of glucagon-like peptide-1
secretion. In addition, curcumin administration is known to
reduce insulin resistance by downregulating phosphorylation of
IRS-1 serine residue and upregulating phosphorylation of IRS-1
tyrosine in the skeletal muscle of rats fed with high fructose.
Curcumin treatment also reduced glucose intolerance,
hyperinsulinemia and homeostasis model assessment-insulin
resistance (HOMA-IR) level. Curcumin treatment decreased C
reactive protein and TNF-levels besides downregulated the
protein kinase theta (PKCh) and COX-2 protein expressions.
Additionally, curcumin significantly downregulated extracellular
kinase 1/2 (ERK 1/2) and p38 protein expressions in skeletal
muscle. Further, curcumin treatment ameliorated the activity of
GPx and attenuated the activation of inflammatory cascades
(Maithilikarpagaselvi et al. 2016). Curcumin treatment
significantly reduced systolic blood pressure, LDL-cholesterol,
triglycerides, aspartate transaminase (AST), alanine
transaminase (ALT), total cholesterol, glycemia, total oxidative
status, MDA and nitrative stress. A recent study demonstrated
that, curcumin administration (100 mg/kg, p.o., daily for 8
weeks) attenuated splenic damage and improved immunity in
streptozotocin-induced diabetic rats via antioxidant,
anti-inflammatory and anti-apoptotic mechanisms (Rashid et
al. 2017). Curcumin treatment is known to attenuate diabetes and
its associated complications like liver disease, adipocyte
dysfunctions, pancreatic beta cell dysfunction, vascular
dysfunction, nephropathy, neuropathy, retinopathy etc. (Zhang et
al. 2013b). In cell culture studies, curcumin treatment
suppressed palmitate-mediated insulin resistance, inhibited the
ubiquitin-proteasome system, reduced the endoplasmic reticulum
(ER) protein aggregation and activated the autophagy signaling
in human umbilical vein endothelial cells (Ye et al. 2017). The
suggested anti-diabetic mechanisms of curcumin effects are
ameliorating b-cell dysfunction, insulin signaling, glucagon
like peptide-1 secretion, and reducing glucose intolerance,
hyperglycemia, hyperinsulinemia, HOMA-IR level, hyperlipidemia,
islet apoptosis and necrosis etc. Therefore, these finding
demonstrate that curcumin supplementation in diabetic population
may be beneficial. |
|
How may Curcumin work against
CANCER? |
In recent
years, in-depth studies of cancer progression have revealed that
curcumin suppresses tumors by interfering with all aspects of
tumor progression, which is the action of some of the most
promising anticancer drugs. First, at the root of cancer
progression, curcumin has been shown to elevate the
ubiquitination level of TAZ that increases proteasome-degrading
TAZ protein, thereby activating the hippo pathway and negatively
regulating cancer stem cell function. Additionally, curcumin
significantly impedes the self-healing of circulating cancer
stem cells, limiting stem cell metastasis. Curcumin also alters
the expression of more than 700 genes linked to carcinoma
development, such as those involved in DNA recovery or
associated with the cell cycle, cell proliferation, or
metastasis in NCI-H460 human lung cancer cells. Researchers
revealed that curcumin not only changes the expression of many
genes, but also alters signaling pathways. Through further
investigation, it was found that those curcumin-altered genes
induce cell death and control extracellular matrix receptors,
repressing NSCLC cell proliferation and migration. These
observations indicate that curcumin governs NSCLC tumor growth
and exhibits cytotoxic mechanisms at the genetic level. Curcumin
possesses various biological activities, such as anticancer
effects on various cancers, such as breast, liver, lung, gastric
and prostate cancers. The anticancer effects of curcumin have
been extensively studied in different cancers, such as breast,
lung, colorectal, head and neck, gastric, bladder, prostate,
thyroid, liver, ovarian, oral, pancreatic, cervical, tongue and
brain cancers. Because of its multitargeting activities, curcumin
has exhibited activities against numerous cancer types in human
clinical trials. Probably the first indication of curcumin’s
anticancer activities in human participants was shownby
Kuttan and co-workers, who conducted a clinical trial involving
62 patients with external cancerous lesions. Curcumin was found
to produce remarkable symptomatic relief as evidenced by
reductions in smell, itching, lesion size, and pain. Kuttan and
his colleague’s work was the first to demonstrate curcumin’s
anti-cancer potential in both in vitro and in vivo experimental
models (Kuttan et al., 1985). Curcumin activates DNA damage
response, laying the foundation for the therapeutic use of these
nutraceuticals in prostate cancer chemoprevention (Horie, 2012).
The general anti-carcinogenic effect of curcumin involves
mechanisms like induction of apoptosis and inhibition of
cell-cycle progression in rat aortic smooth muscle cells (Chen
and Huang, 1998). The antiproliferative effect is regulated
partly through hindrance of protein tyrosine kinase activity and
c-myc mRNA expression, while the apoptotic effect may partly be
mediated via preventing the functioning of protein tyrosine
kinase, protein kinase C, and expressions of c-myc mRNA and
bcl-2 mRNA (Chen and Huang, 1998). Curcumin inhibits the
transcription factor NF-κB (Figure 6) and various downstream
gene products like c-myc, Bcl-2, COX-2, nitric oxide synthase
(NOS), Cyclin D1, TNF-α, ILs, and matrix metallopeptidase 9
(MMP-9) and has anti-proliferative activities in a diversity of
malignancies. Curcumin, either alone or in combination with other agents, has
demonstrated potential against colorectal cancer, pancreatic
cancer, breast cancer, prostate cancer, multiple myeloma, lung
cancer, oral cancer, and head and neck squamous cell carcinoma. Curcumin was found to exert its anticancer activities
in many different types of cancer cells by regulating a variety of signaling
pathways. Curcumin induces cell death in numerous animal and human
cell lines, including leukemia, melanoma, and carcinomas of the
breast, lung, colon, kidney, ovaries and liver. It appears to
function by caspasedependent and independent (mitochondrial)
mechanisms, which are associated with the presence and absence
of p53. Curcumin has been studied as a beneficial herb in cancer
treatment and been found to affect cancer growth, development
and spread at the molecular level. Studies have shown that it
can contribute to the death of cancerous cells and reduce
angiogenesis (growth of new blood vessels in tumors) and
metastasis (spread of cancer). Multiple studies indicate that
curcumin can reduce the growth of cancerous cells in the
laboratory and inhibit the growth of tumors in test animals.
There is also evidence that it may prevent cancer from occurring
in the first place, especially cancers of the digestive system
like colorectal cancer.
Curcumin is capable of inhibiting the growth
of cancer cells in skin, oral, intestinal, and colon cancers.
Animal models show that not only does curcumin block growth of
cancer cells in these models, but it also increases the number
of cancer-fighting enzymes in the system. A 2011 study
works to quantify the prohibitive properties of curcumin on
cancer cells in head and neck squamous cell carcinomas. This
type of cancer is the 6th most commonly-diagnosed cancer in the
United States. That study showed curcumin not only works as a
treatment for squamous cell carcinomas with incredibly promising
results, but it has also been shown to demonstrate powerful
anti-cancer properties. Part of the excitement surrounding the
potential anti-cancer benefits of curcumin revolves around the
safety of use of the compound. It is considered
pharmacologically safe, which means there are no known drug
interactions or specific reactions among patients, making it
extremely well-tolerated. For more evidence that turmeric with
curcumin in particular being a powerful anti-cancer compound, we
need only look at the rates of cancer in parts of the world
where turmeric is consumed in higher quantities. Over the years, cancer research has
examined the role curcumin plays in treating this disease.
Curcumin is antimutagenic as it potentially helps to prevent new
cancers that are caused by chemotherapy or radiation therapy
used to treat existing cancers. It effectively inhibits
metastasis (uncontrolled spread) of melanoma (skin cancer) cells
and may be especially useful in deactivating the carcinogens in
cigarette smoke and chewing tobacco. Curcumin generates an
anticancer effect by inhibiting nuclear factor kappa B (NF-κB),
and also reduces the formation of glycation end products which
induce inflammation. Curcumin also mediates anticancer activity
by targeting many other enzymes/pathways, maintaining levels of
vitamins C and E, preventing peroxidation of lipid, and DNA
damage. Curcumin targets transformed cells without altering
primary astrocytes. It also promotes apoptosis, and shows a
synergistic effect in combination cisplatin and doxorubicin
drugs. An active constituent of turmeric suppresses
carcinogenesis in multiple human carcinomas, which include
ovarian cancers, stomach cancer, colon cancer, breast cancer,
head and neck cancer. Curcumin suppresses the carcinogenesis by
targeting diverse molecular targets of cellular division and
apoptosis. The beneficial effects of curcumin on various
transcription factors, oncogenes, and signalling proteins are
well known. It also targets various stages of carcinogenesis
from the initial stage to tumorigenesis, growth, invasion, and
metastasis. Animal studies involving rats and mice as well as in
vitro studies utilizing human cell lines have demonstrated
curcumin's ability to inhibit carcinogenesis at three stages:
Tumor promotion, angiogenesis, and tumor growth. In two studies
of colon and prostate cancer, curcumin inhibited cell
proliferation and tumor growth. The anticarcinogenic effects of
turmeric and curcumin are due to direct antioxidant and
free-radical scavenging effects and their ability to indirectly
increase glutathione levels, thereby aiding in hepatic
detoxification of mutagens and carcinogens and in inhibiting
nitrosamine formation. A number of laboratory studies on cancer
cells have shown that curcumin does have anticancer effects.
These studies have found that curcumin can significantly inhibit
the growth, development and movement of cancer throughout the
body. It seems to be able to kill cancer cells and prevent more
from growing. It has the best effects on breast cancer, bowel
cancer, stomach cancer and skin cancer cells. An American study
that combined curcumin with chemotherapy to treat bowel cancer
cells in a laboratory showed that the combined treatment killed
more cancer cells than the chemotherapy alone. Another American
study seemed to show that curcumin helped to stop the spread of
breast cancer cells to other parts of the body. Doctors think
that curcumin stays in the digestive system and is absorbed by
the cells in the bowel. Several studies have shown that curcumin
taken as capsules does get absorbed by the gut and is present in
the blood. One of the mechanisms by which it does this is
reducing the growth of new blood vessels in tumors (otherwise
known as angiogenesis) and can also directly contribute to the
death of cancerous cells. Scientists discovered that turmeric is
effective in killing cancer cells and also preventing their
growth. According to the American Cancer Society, tests indicate
that curcumin "interferes with several important molecular
pathways involved in cancer development, growth and spread" and
has boosted the effects of chemotherapy in animals. Curcumin has
the potential for treatment of cancers including colon, breast,
prostate, lung, skin and bowel. Curcumin shows a strong ability
to kill cancer cells as well as inhibit their growth, boost
antioxidant levels and balance the immune system. It seems to
work on improving mitochondrial function at a cellular level.
Even against drug-resistant strains of leukemia, curcumin caused
cell death of cancer cells. Curcumin has been shown to
substitute chemotherapy for colorectal cancers, and in
multidrug resistant cancers. The ability of curcumin to regulate
a variety of signaling pathways involved in cell growth,
apoptosis, invasion, metastasis, and angiogenesis in preclinical
studies elicited scientific interest in its potential as an
anticancer agent in tumor therapy. Curcumin is one of the most
powerful and promising chemopreventive and anticancer agents,
and epidemiological evidence demonstrates that people who
incorporate high doses of this spice in their diets have a lower
incidence of cancer. Curcumin's epigenetic modulation has been
studied by the US National Cancer Institute (NCI) and academic
investigators around the world. Because of low toxicity and
great efficacy in multiple in vitro and in vivo cancer models,
Curcumin was selected for further development, put through
extensive toxicology testing and has successively made it
through the first stages (Phase I) of clinical testing abroad
and is currently in clinical trials at several sites in the U.S.
A phase I clinical trial looked at giving curcumin to 25
patients with pre cancerous changes in different organs. This
study seemed to show that curcumin could stop the precancerous
changes becoming cancer. Numerous mechanisms have been described
for the anticancer activity of Curcumin. Curcumin inhibits the
NF-ŒB and STAT3 signaling pathways, which play key-roles in the
development and progression of cancer. It inhibits a highly
expressed transcription factor Sp-1 and its downstream genes,
including ephrin type-B receptor 2 precursor, HDAC4, calmodulin
and ADEM10 which serve as an important mechanism to prevent
metastasis. Curcumin enhances the expression of several
extracellular matrix components and inhibits the phosphorylation
of focal adhesion kinase (FAK) and CD24 expression, thus
prevents cancer formation, migration and invasion (Vallianou et
al. 2015; Shi et al. 2001; Zhou et al. 2013). In addition, the
potential mechanism of the anti-invasive effect of curcumin
includes downregulation of Akt, EGFR, cyclin D1, cMET and
upregulation of DNAJ/heat shock protein (HSP) 40 chaperone.
Recent studies revealed that ER stress and autophagy might
involve in apoptosis process. Mechanistically, autophagy
inhibition could increase curcumin induced apoptosis by inducing
ER stress (Vallianou et al. 2015). Further, the anticancer
effects induced by phytoconstituent curcumin in malignant cells
are mediated via the modulation of multiple signaling pathways
and its effectors. Curcumin induced anti-carcinogenic effects
includes down-regulation of the insulin-like growth factor
type-1 receptor (IGF-1R), EGFR/avian erythroblastosis oncogene
B1 (erbB1), erbB2/human epidermal growth factor receptor 2
(HER2), Wnt/b-catenin and sonic hedgehog/glioma associated
oncogene (SHH/GLIs), and their respective downstream signaling
effectors. Curcumin modulates intra-cellular signal transduction
elements such as p21, p27, inhibitor of growth family member 4
(ING4), cyclin D1, c- Myc, VEGF, ICAM-1, MMPS, uPA, COX-2,
CXCR-4, Bax, Bad, Bak, Noxa, p53, modulator of apoptosis,
caspases etc. resulting in reversal of cancer incidence,
progression and relapse (Figure 4) (Jordan et al. 2016; Mimeault
and Batra 2011; Kasi et al. 2016). A2012 study
indicates that rates of colorectal cancer in India are among the
lowest in the developed world. Another study from 2016 shows
that Indian women are less likely to be diagnosed with breast
cancer, as well. Part of the reason for the lowered cancer rates
in India has been attributed to diet, with turmeric and curcumin
being major dietary contributors in that part of the world.
Combining curcumin with anticancer
drugs like gemcitabine in pancreatic cancer, docetaxel in breast
cancer, and imatinib in chronic myeloid leukemia may be safe and
well tolerated. A recent single-arm, phase II trial combining
three cycles of docetaxel/prednisone and curcumin (6 g/day) was
carried out in 26 patients with castration-resistant prostate
cancer. The level of prostate-specific antigen (PSA) was
decreased in most patients and was normalized in 36% of them,
and the co-administration of curcumin with drugs showed no
toxicity beyond adverse effects already related to docetaxel
monotherapy. Many registered phase I/II clinical trials designed
to investigate the effectiveness of curcumin alone or with
first-line treatment in patients with breast, prostate,
pancreatic, lung, or colorectal cancer are under way. Research
into preventing cancer: A phase I clinical trial looked at
giving curcumin to 25 patients with pre-cancerous changes in
different organs. This study showed how curcumin could stop the
precancerous changes becoming cancer. A number of laboratory
studies on cancer cells have shown that curcumin does have
anticancer effects. It kills cancer cells and prevent more from
growing. It has the best effects on breast cancer, bowel cancer,
stomach cancer and skin cancer cells. A study that
combined curcumin with chemotherapy to treat bowel cancer cells
in a laboratory showed that the combined treatment killed more
cancer cells than the chemotherapy alone. An American study
in mice showed that curcumin helped to stop the spread of breast
cancer cells to other parts of the body. Doctors think that
curcumin stays in the digestive system and is absorbed by the
cells in the bowel. Several studies have shown that curcumin
taken as capsules does get absorbed by the gut and is present in
the blood. A number of activities of curcumin, which are exerted
in a chemopreventive and a directly therapeutic manner, indicate
that it may be a potential anticancer remedy. Researchers at
M.D. Anderson Cancer Center in Houston, TX state that Curcumin
has “enormous” potential to prevent and treat cancer. Curcumin
was able to suppress tumor formation, growth, and even
metastasis according to their review. Currently, there are
clinical trials being conducted on the effects of Curcumin on
patients with bowel cancer. According to the American Cancer
Society, tests have shown that curcumin can kill cancer cells in
laboratory dishes, and also slow the growth of the surviving
cells. Furthermore, it has been found to reduce the development
of several forms of cancer in lab animals, while also shrinking
various animal tumors. A review -
Anticancer Potential
of Curcumin: Preclinical and Clinical Studies - in Anticancer Research
concluded that, "…it is quite apparent that curcumin has tremendous
potential for prevention and therapy of various cancers." Another study on
the role of curcumin in cancer therapy
found that, curcumin is a potent anti-inflammatory agent
with strong therapeutic potential against a variety of cancers. Curcumin has
been shown to suppress transformation, proliferation and metastasis of
tumors, and called for additional and larger controlled studies to
determine its full potential. Inhibition of proliferation
of tumor cells, induction of apoptosis (a mode of cell death), inhibition of
transformation of cells from normal to tumor, inhibition of invasion and
metastasis and suppression of inflammation have been linked with the
activity of curcumin. Resistance to chemo and radiotherapy is the major reason
for cancer relapse. This arises due to the presence of a
subpopulation of cancer cells, having self-renewal capabilities
called Cancer Stem Cells (CSCs). Studies have confirmed that
curcumin could inhibit the breast cancer stem cell population by
downregulating the expression of stem cell genes Oct4, Sox2 and
Nanog and also the Epithelial-Mesenchymal Transition (EMT) as
observed by the down-regulation of mRNA levels of Vimentin,
Fibronectin and β-catenin and up-regulation of mRNA levels of
E-cadherin (Hu et al., 2019). A combination of sub-optimal dose
of 5-FU and curcumin elicits synergistic antitumor potential in
murine models as evaluated by a reduction in the tumor-related
parameters. Mechanistically, curcumin down-regulates 5-FU
induced up-regulation of Thymidylate Synthase (TS), which is
responsible for 5-FU chemoresistance (Vinod et al., 2013;
Haritha et al., 2021). Another study reported that cervical
cancer cells can be sensitized by curcumin to paclitaxel-induced
apoptosis through down-regulation of NF-κB, Akt and Bcl2 (Bava
et al., 2011). The chemopreventive agent curcumin also act as a
potent radiosensitizer in human cervical tumor cells. Curcumin
pre-treatment increased reactive oxygen species production and
overactivation of the mitogen-activated protein kinase pathway
in HeLa and SiHa cells when treated with Ionising Radiation (Javvadi
et al., 2008). Mechanism of action of curcumin mainly
involves down-regulation of transcription factor NF-κB by
inhibition of Notch signalling, which is involved in cell
proliferation, apoptosis, maintenance of stem cell and their
renewal. This results in a reduction in expression of NF-κB
regulated genes, which includes Bcl-2, cyclin D1 and VEGF (O’riordan
et al., 2005). Curcumin is a strong inhibitor of Protein Kinase
C (PKC) and several oncogenes such as c-jun, c-fos, c-myc, NIK,
MAPKs, ERK, ELK, PI3K, Akt and CDKs. Curcumin also inhibits of
the Notch-1 downstream target Hes-1 in esophageal cancer cells.
Hes-1 is an important notch signalling target and mediator (Subramaniam
et al., 2012). The curcumin analog, 2-pyridylcyclohexanone has
also been shown to decreases basal STAT3 phosphorylation and
promotes apoptosis in esophageal cancer cell, ESCC cells (Wang
et al., 2018). Curcumin quenches free radicals, induces
antioxidant enzymes (catalase, superoxide dismutase, glutathione
peroxidase), and up-regulates antioxidative protein markers,
Nrf2 and HO-1 that led to the suppression of cellular oxidative
stress. In cancer cells, curcumin aggressively increases ROS
that results in DNA damage and subsequently cancer cell death (Ak
and Gülçin 2008). Curcumin was found to suppress inflammatory
cytokines such as IL-6, IL-8, granulocyte macrophage colony
stimulating factor and TNF-α as well as IKKβ kinase in the
saliva of HNSCC patients. Kim SG., et al., also suggested that
IKKβ kinase could be a plausible biomarker for the detection of
the effect of curcumin in head and neck cancer as curcumin
inhibited IKKβ kinase activity and this resulted in the reduced
expression of a number of cytokines (Kim et al., 2011).
Molecular docking studies further aids in identifying the role
of curcumin in numerous signalling cascades involved in
carcinogenesis and confirms the already suggested molecular
mechansims responsible for the chemopreventive efficacy of
curcumin. Using inverse molecular docking several proteins
associated with cell proliferation and tumor formation namely,
macrophage colony stimulating factor 1 receptor, aldo-keto
reductase family 1 member C3, amiloride-sensitive amine oxidase
and tyrosine-protein phosphatase non-receptor type 11 were
identified as potential targets of curcumin. Curcumin was
previously reported to inhibit the NFkB mediated activation of
genes linked to cell survival and proliferation (Divya and
Pillai 2006). Proteins such as MMP-2, NAD-dependent protein
deacetylase sirtuin-2, core histone macro-H2A.1, NAD-dependent
protein deacetylase sirtuin-1 and epidermal growth factor
receptor were also revealed to be targets of curcumin, the
binding of which regulates the activity of NF-kB (Furlan et al.,
2018). These results provide a mechanistic explanation for the
anticancer effects of curcumin. Targeting Phosphodiesterase 4
(PDE4) has been reported to be a potential therapeutic strategy
against inflammatory disorders (I Sakkas et al., 2017). Studies
suggest that curcumin may exhibit its anti-cancer property
through the inhibition of PDE2 and PDE4 (Abusnina et al., 2015).
Furlan et al. also gives evidences for the inhibitory effect of
curcumin on PDE4 (Furlan and Bren 2021). Curcumin as an Anti-Inflammatory
| It has been observed
that chronic inflammation is responsible for several diseases,
such as tumor progression, autoimmunity, allergies, and
arthritic syndromes. Numerous researches revealed that curcumin
can decrease pro-inflammatory cytokines such as IFN-γ, TNF-α,
IL-1, and IL-8 by interfering with several signaling and
transcription factors such as NF-кB, JAKs/STATs, and MAPK
pathways (64). The anti-inflammatory activity of curcumin mainly
depends on its potentiality to inhibit NF-kβ activation.
Curcumin inhibits inflammation by downregulating cytokines,
IL-1, IL-8, and TNF-α. Curcumin blocks TNF-mediated NF-кB
activation in human myeloid ML-1a cells by suppressing activator
proteins. Curcumin also blocks NF-кB activation by hydrogen
peroxide and phorbol esters. IL-1β-mediated ICAM-1 and IL-8 gene
expression are also inhibited by curcumin, which finally leads
to the inhibition of NF-кB activation. JAK/STAT is an important
signaling pathway in maintaining inflammation in immune cells.
It transduces signal type 1 and 2 cytokine receptors in response
to pro-inflammatory cytokines. Curcumin inhibits JAK/STAT
pathway by blocking the phosphorylation of JAK-1 and -2 and
STAT-1 and -2 in IFN-γ, gangliosides, and LPS-activated
microglial cells. Curcumin has a distinct role in the
inflammatory MAPK pathway. Curcumin significantly lowers the
PGE2 (prostaglandin E2) level and the expression of TNF-α and
IL-6 by preventing phosphorylation and activation of p38 MAPK
functioning. Curcumin can suppress LPS-induced phosphorylation
of p38, JNK, and ERK1/2-mediated MAPKs pathways and subsequently
inhibit the ROS production by microglial cells (70). Kim et al.
validated that if immature DCs cells pre-treated with curcumin,
it blocked the LPS-induced maturation function of DCs by
preventing phosphorylation of p38-, JNK-, and ERK1-/2-mediated
MAPK signaling, which consequently checks the inflammation
occurrence .It is well
known that the human body is capable of self-healing after a
short-term inflammatory response, but long-term chronic
inflammation could lead to initiation of the cancer process.
Many studies have shown that inflammatory factors (including
interleukins, TNF-α, NF-ϰB) and the ROS production-induced
inflammation infiltrate the inflammatory microenvironment
leading to DNA damages and ultimately initiation of cancer. By
acting on several signaling pathways, especially the
WNT/β-catenin pathway, curcumin can have anticancer effect by
inhibiting chronic inflammation and oxidative stress. The
chronic inflammatory microenvironment of tumors could also be
targeted by curcumin. Immunomodulatory Role of
Curcumin | Curcumin can inhibit the expansion of T
cells triggered by plant lectin concanavalin A (Con A),
according to a report on the role of the genus Curcuma and its
bioactive metabolites to control the immunological response.
Curcumin inhibits lymphoma B-cell proliferation by lowering the
potency of c-MYC, BCL-XL, and NF-κB. Curcumin has also been
demonstrated to suppress the production of ROS in macrophages.
Curcumin also stimulates NK cell apoptosis by modulating the
NF-κB pathway and inhibiting BCL-XL and Cyclin D. Curcumin
inhibits IL-1 and IL-6 inflammatory cytokines such as from
LPS-stimulated dendritic cells and suppresses the expressions of
CD80, CD86, and MHC class II by dendritic cells. Curcumin also
causes reduced LPS-induced MAPK activation and NF-κB p65
translocation in dendritic cells (Nair et al., 2017) along with
impaired activation of Th1 responses. Curcumin significantly
suppressed the formation of IL-6, IL-8, TNF-α, and MCP-1 from
higher glucose-cultured monocytes, according to Jain et al.
(2009). Curcumin decreased NOS activity and macrophages’ ability
to secrete nitric oxide (NO). In the management of immune modulation,
curcumin treatment can promote the activation of immune
component cells, including reduce excessive activation of
inflammation and allergy, and enhance endogenic immune activity
to fight foreign pathogens or cancer cells. Remarkably, curcumin
can suppress intracellular NF-κB, MAPKs, JAKs/STATs, β-catenin,
and the Notch-1 pathway by regulating the expression and
secretion of pro-inflammatory cytokines, such as IL-1β, TNF-α,
IL-2, IL-6, IL-10, which mediate inflammatory pathways. In the
managements of clinical treatment, curcumin can also be applied
to autoimmune diseases therapies, such as lupus erythematosus,
rheumatoid arthritis, ankylosing spondylitis, psoriasis, etc.
Curcumin treatment can restore cellular immune-reactive T cells
and assist the body to fight endogenous cancer cells and
exogenous pathogens. In vitro and in vivo data showed curcumin
can hinder cancer cell proliferation or cause cancer cell
apoptosis. Curcumin as an immunomodulator interacts not
just with various cellular components, such as DCs, macrophages,
natural killer cells, and both B and T lymphocytes, but also
with modulatory molecules involved in the processes of
inflammation and cell proliferation with their downstream
signaling. In recent times, curcumin has gained the potential
therapeutic interest to cure neoplastic disease, because of its
significance as an anti-inflammatory and anti-proliferative
substance. The anti-cancer properties of curcumin also modulate
several other signaling pathways involved in mutagenesis,
oncogene expression, cell cycle regulation, apoptosis,
angiogenesis, and metastasis. The effectiveness of curcumin has
been proven in the restoration of CD4+ and CD8+ cells in the TME
and in directing Th2 cytokine bias towards Th1-type response
again. It increases Th1-type immune responses and upregulates
IFN-γ mRNA expression. Curcumin effectively reduces Treg cell
population and levels of IL-10 and TGFβ. It also can reduce the
expression of CTLA4 and FOXP3 both at protein and mRNA levels
(55). Interestingly, curcumin has the potentiality to encounter
all “six hallmarks” of cancer cells and checks tumor outgrowth
in the host. Hence, it is considered very interesting to
envision the role of curcumin concerning cancer immunotherapies
as an immunomodulator. Effects of Curcumin on Immune
Cells | Curcumin has the potentiality to
modulate the proliferation and activation of T cells. Depending
on the dose, it can both suppress and induce the proliferation
of T cells. Several studies reported that curcumin downregulates
the proliferation of T cells induced by concanavalin A (Con A),
phytohemagglutinin (PHA), and phorbol-12-myristate-13-acetate
(PMA). Tomita et al. reported that curcumin can suppress the
proliferation of HTLV-1-infected T cells and primary ATL cells
through cell cycle arrest and induction of apoptosis. Research
carried out by Hussain et al. stated that in T cell acute
lymphoblastic leukemia, curcumin blocks constitutively activated
targets of PI3-kinase (AKT, FOXO, and GSK3) in T cells, which
lead to the inhibition of proliferation and induction of
caspase-dependent apoptosis. On B cell: Curcumin prohibits the
proliferation of B-cell lymphoma cells via downregulation of
c-MYC, BCL-XL, and NFκB activities. It also blocks Epstein–Barr
virus (EBV)-induced immortalization of B-cells. On macrophage:
Curcumin modulates macrophage activities, prevents generation of
ROS in macrophages, and stimulates enhanced phagocytosis of
peritoneal macrophages in mice. On Natural Killer cell: Curcumin
works against natural killer T cell lymphoma cell lines, where
it induces apoptosis by controlling the NFκB pathway and
suppression of BCLXL, Cyclin D1, etc.. On DC: Curcumin can
reduce the expression of CD80, CD86, and class-II antigens by
DCs. Curcumin suppresses the release of inflammatory cytokines
like IL-1β, IL-6, and TNF-α from LPS-stimulated DCs. Curcumin
also modulates phosphorylation of MAPK and nuclear translocation
of NFκB in DCs. Curcumin as an Anti-Proliferative and
Anti-Metastatic Substance | Curcumin acts upon numerous
cell proliferation signaling pathways that are intensely
associated with cancer progression. Curcumin inhibits NF-кB
signaling by suppressing IкB kinase activity. Curcumin
suppresses the other proliferation signaling pathways, such as
PI3K, AKT, mTOR, AP1 (JUN and FOS), JNK, JAK/STAT, PKC, CMYC,
MAPK, ELK, CDKs, iNOS, and Wnt/β-catenin, which confirmed its
vital role in the prevention of cancer progression. Cyclin D1,
the proto-oncogene that is highly expressed in several types of
cancer and acts in cell cycle progression and proliferation, is
also suppressed by curcumin. Along with this, curcumin also
inhibits excessive TGFβ receptor signaling and EGF- and
EGFR-mediated signaling pathway and remarkably controls
epithelial-to-mesenchymal transition, metastasis, and tumor
progression, respectively. A significant activity of the
telomerase enzyme has been observed in cancer cells, which
prevents telomere shortening and stimulates continuous cell
proliferation signaling. Curcumin prevents human telomerase
(hTERT) activities and reduces hTERT-mRNA expression that led to
telomere shortening. By targeting telomerase activities,
controlling replicative cell senescence and mortality, curcumin
ultimately controls the uncontrolled cell proliferation of
cancer cells. Numerous studies have reported the incredible
potentiality of curcumin to inhibit cell migration, invasion,
and colony formation in vitro and decrease tumor growth and
metastasis in vivo. Curcumin downgrades the expression of matrix
metalloprotease, CCRX4, COX2, ELAM1, and ECAM1, which are
essential for metastasis. Besides, curcumin also hampers the
functioning of SLUG, SNAIL, FAK, TWIST, and other essential
transcription factors that play a crucial role in the metastasis
process. Curcumin as an Apoptotic and Anti-Angiogenic
Substance
Curcumin has been suggested as an enhancer of apoptosis in
cancer cells. It has the ability to modulate a wide range of
signalling pathways involved in apoptosis resistance in cancer
cells. Curcumin also triggers programmed cell death in colon
cancerous cells and inhibits micro-inflammation in the
gastrointestinal system linked to inflammatory bowel illnesses,
according to laboratory research (Nita, 2003). Okanlawon et al.
(2020) determine the influence of the inclusion of powdered C.
longa on carcass yield and intestinal increase in rabbit
production. Farombi et al. (2007) explored the combined effects
of curcumin and kolaviron (a bioflavonoid extracted from
Garcinia kola seeds) on DBP-induced testicular injury in rats.
Curcumin treatment of mice infected with human prostate cancer
cells resulted in a lowered microvessel density, cell
proliferation, an improvement in apoptosis. Endothelial cells
derived from bovine aorta exposed to curcumin (5–15 μM) under
normoxic (oxygen tensions within 10–21%) or hypoxic (oxygen
tensions within 1–5%) conditions were reported to increase heme
oxygenase activity and resistance to oxidative stress.
Consumption of alcohol sensitizes the pancreas to give an
inflammatory response through NF-κB activation via protein
kinase C epsilon. One pilot study concluded that an oral dosage
of 500 mg of curcumin with 5 mg of piperine could restore lipid
peroxidation in patients suffering from tropical pancreatitis (Durgaprasad
et al., 2005).A common property for most cancer cells is
some mutations in tumor suppressor genes, especially p53 and
PTEN. Mutations in these genes lead to them escaping cell death
and also resistance to therapy. Curcumin has the ability to
reverse the activities of both p53 and PTEN. Inhibition of
mir-21 has a key role in the activation of PTEN, leading to
inhibition of the PI3K/AKT pathway. Suppression of AKT following
treatment with curcumin can cause degradation of MDM2, which
leads to activation of p53. Furthermore, suppression of AKT can
reduce the expression of anti-apoptotic genes such as COX-2,
NF-κB and Bcl-2. Downregulation of these genes by curcumin has
shown its potential to sensitize a wide range of cancer cells to
chemotherapy and radiotherapy. In addition to the regulation of
a wide range of genes in cancer cells, curcumin has been shown
to modulate the tumor microenvironment in favor of tumor
suppression. Inhibition of some immunosuppressive cells'
cytokines such as IL-10 and TGF-β leads to more infiltration and
proliferation of NK cells and CTLs as well as inhibition of
tumor-promoting cells including TAMs, CAFs and Tregs. These
immunoregulatory effects of curcumin lead to the release of dead
signals such as FasL and TNF-α for cancers. Upregulation of Fas,
TNFR and TRAIL because of elevated ROS production by cancer
cells can facilitate apoptosis pathways following treatment with
curcumin. Curcumin blocks the
phosphorylation of another tumor suppressor protein, RB
(Retinoblastoma), which plays a significant role in the cell
cycle process. Curcumin induces both TP53-dependent and
-independent apoptosis of cancer cells by upregulating
pro-apoptotic molecules such as BAX, BIM, and PUMA and by
downregulating anti-apoptotic molecules like BCL2, BCL-XL, and
Survivin. Consequently, the caspase activity gets enhanced and
proceeds to apoptosis. Besides, curcumin stimulates lysosomal
proteases, phosphatases, and lipase activities, which induce
autophagy-mediated cell death. Blocking the angiogenesis process
is a vital step to control tumor outgrowth. Curcumin suppresses
VEGF receptor (VEGFR1 and VEGFR2) expression, blocks
VEGF/VEGFR-mediated signaling pathway, and downregulates
angiopoietin expression to confine angiogenesis. In vitro and in
vivo studies have indicated that curcumin prevents
carcinogenesis by affecting two primary processes: angiogenesis
and tumor growth. Turmeric and curcuminoids influence tumor
angiogenesis through multiple, interdependent processes: i)
action at the level of transcription factors associated with
inflammatory processes and early growth response protein which
reduces the expression of IL8 in pancreatic and head and neck
cancer cell lines and prevents the induction of VEGF synthesis;
ii) inhibition of angiogenesis mediated by NO (nitric oxide) and
iii) inhibition of COX2 and 5LOX; iv) action at the level of
angiogenic factors: VEGF, the primary factor for migration,
sprouting, survival and proliferation during angiogenesis, and
basic fibroblast growth factor. Because of its anti-apoptotic
and antiproliferative efficacy, its ability to interfere with
several tumor progression associated signaling pathways, and to
modulate tumor-associated miRNA expression, curcumin is regarded
as antitumorigenic. In addition, curcumin prevents formation of
breast and prostate metastases in vivo. The review by
Willenbacher et al. in this issue summarizes some papers that
have been published in the field of curcumin’s antitumorigenic
effects. Curcumin is also potent against cancer types that are
difficult to treat, like melanoma or glioblastoma, as
demonstrated by the work of Maiti et al. in this issue. An
American phase 2 study reported in 2008. 25 patients had
curcumin treatment and 21 had tumors that could be measured. In
2 patients their tumors shrank or remained stable. In some
patients their levels of particular immune system chemicals that
destroy cancer cells went up. Curcumin also has been studied
with regards to the core inflammatory gene signal,
NF-kappaB, resulting in a beneficial domino effect throughout the
body. One benefit of this domino effect is a direct reduction in
the risk of cancer from overweight-induced inflammation.
Curcumin has been found to induce cell-cycle arrest and
apoptosis by regulating a variety of cell-signaling pathways (3,
41-45). For example, the inhibition of cell proliferation by
curcumin has been associated with the Nrf2-dependent
downregulation of DNA repair-specific flap endonuclease 1 (Fen1)
in breast cancer cells in culture. Curcumin has been shown to
induce p53-dependent or -independent apoptosis depending on the
cancer cell type. In a panel of cancer cell lines,
p53-independent apoptosis induced by curcumin was mediated by
the rapid increase of ROS and the activation of MAPK and c-jun
kinase (JNK) signaling cascades. Inhibition of NF-κB signaling
by curcumin also suppresses proliferation and induces apoptosis
in cancer cells. Effect of Curcumin on
Chemoresitance | Curcumin has a proven ability to
counter chemoresistance in cancer cells. The ability of curcumin
to modulate the regulatory networks governing the balance of
cell survival and induction of cell death is well established.
Curcumin has been demonstrated to amend the expression of
molecules central to chemoresistance including members of the
ABC drug efflux transporter family. Curcumin modulates the
cancer metabolism and bio-physiological composition of the
extracellular milieu culminating in the induction of cell death
and retardation in disease progression. Metabolic alterations
and suppression of receptor-mediated signaling were suggested to
provide chemosensitization of cancer cells by curcumin. The
previous investigation on hepatic carcinoma cells demonstrated
that curcumin can thwart lactate-induced chemoresistance.
Interestingly, curcumin can be exploited to provide health
benefits in diabetes mellitus owing to its antioxidant and
anti-inflammatory capabilities. In renal tubular epithelial
cells, curcumin was also shown to obviate high glucose-induced
epithelial-to-mesenchymal transition. High glucose conditions
can aggravate the invasion and migration, while curcumin can
impede the metastatic events in a variety of malignancies.
Antineoplastic potential, metabolic modulatory ability, and
chemosensitizing property along with safety investigations
provide an edge to curcumin over other phytochemicals. Curcumin
has the ability to avert high glucose-induced chemoresistance in
cancer cells. Various aspects of the underlying mechanism were
also explored. Curcumin mediated the amputation of
chemoresistance by repressing the hyperglycolytic behavior of
malignant cells via modulated expression of metabolic enzymes
(HKII, PFK1, GAPDH, PKM2, LDH, SDH, IDH, and FASN), transporters
(GLUT-1, MCT-1, and MCT-4), and their regulators. Along altered
constitution of extracellular milieu, these molecular changes
culminated into improved drug accumulation, chromatin
condensation, and induction of cell death. Molecular alterations
in the expression level of transcription factors (p53, HIF-1α,
MYC), drug efflux pumps (MDR-1), and their regulators (HCAR-1,
mTOR, and STAT3) can be suggested as the underlying molecular
mechanism. This investigation contributed to the understanding
of the anticancer ability of curcumin through the prevention of
chemoresistance in hyperglycemic conditions along with
underlying mechanisms. The demonstrated potential of curcumin
against high glucose-induced chemoresistance will have
implementations in clinical management of malignancies in
diabetic patients.
Curcumin as an Anti-Tumor Substance | The anti-tumour
activity of curcumin is mediated via anti-inflammatory,
apoptosis-inducing, anti-oxidative and anti-angiogenic
activities. In colon cancers, the anti-tumour activity of
curcumin was mediated via inhibition of COX-2. P53
(apoptosis-inducing in stressful situations) has been shown to
have a varied response to curcumin administration;
overexpression in human hepatoblastoma, human breast cancer
cells and human basal cell carcinoma and downregulation in
colorectal carcinoma reveal that it may be tissue-specific. Its
anti-angiogenic effect is by inhibition of angiogenic factors
like fibroblast growth factor (FGF), ligands of VEGF and
angiopoietin 1 and 2 and regulation of cell adhesion molecules
like endothelial adhesion molecule-1 (ELAM-1), intracellular
adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
(VCAM-1) and cell surface proteins that are involved in tumour
metastasis. Implementation of
curcumin reduces cell mutations caused by exposure to
carcinogens and induces the body's anti-tumor responses.
Curcumin can promote M1-like tumor microglia activation and
increase recruited natural killer cell to cause tumor
decimation. Curcumin can inhibit the cancer cell proliferation
by inhibit NF-κB, COX-2, CD-31, VEGF, and IL-8, matrix
metalloproteinase (MMP)− 9. Turmeric extract or curcumin
can inhibit the proliferation of cancer cells such as head and
neck cancers, lung cancer, digestive system cancer,
urinary system cancer, and reproductive system cancer in vitro
and in vivo. The oral submucosal fibrosis, which is highly
associated with oral cancer, is a chronic latent disease that
leads to the hardening of the oral mucosa and deep tissues, and
extends to the wall of the throat or esophagus, gradually
causing difficult or loss of eating, swallowing, and
pronunciation. In clinical management of oral mucosal fibrosis,
curcumin is evident to treatment can prevent, reduce, and
improve oral mucosal fibrosis. Curcumin treatment can increase
the levels of vitamins C and E in salivary and serum to enhance
organism’s antioxidative values, and decrease the malonaldehyde,
8-hydroxydeoxyguanosine (8-OHdG) to decrease oxidative stress.
In clinical application, curcumin is used as an adjuvant or
supplement for chemotherapy or nuclear therapy in clinical tumor
treatments to reduce postoperative adverse reactions, which
still requires clinical verification. Curcumin has
multiple potentials due to its numerous antineoplastic
mechanisms for cancer therapy. Curcumin, a chemo-sensitizing
agent, also enhances the efficacy of several chemotherapeutic
agents. According to the study by Chen’s group, among four
anticancer chemotherapeutic factors (erlotinib, sorafenib,
sunitinib, and doxorubicin), sunitinib combined with curcumin at
a molar ratio of 0.46 achieved the most potent synergistic
effect in vitro and has been selected to be studied in an animal
model. The anti-tumor effects of curcumin or turmeric extract in
combination with bevacizumab in HT29 colon tumor-bearing mice
have been examined by Yue’s group. When curcumin is combined
with bevacizumab therapy, it suppressed tumor growth
significantly with no physical side effects. This highly
indicates the therapeutic promise of adjuvant application of
curcumin for treating cancer, particularly combined with several
mAbs. A clinical trial has been executed by Basak et al. with
oral cancer patients where APG-157, a botanical drug containing
multiple polyphenols, including curcumin has been administrated
orally. According to the study, APG-157 was absorbed well and
significant trace of curcumin has been found in the blood and in
tumor tissues. This trial reported the downregulation of
inflammatory markers and Bacteroides species in the saliva and
upregulation of the immune T cells in the tumor tissue.
Additionally, it reduced inflammation and attracted cytotoxic T
cells to the tumor site, signifying its potential usage in
combination with immunotherapy drugs. Curcumin alone induced a 49–55% reduction in mean ovarian
cancer tumor growth compared with control animals, while the
combination of curcumin with docetaxel resulted in a 77%
reduction in mean tumor growth compared with the controls. In an
animal study, the administration of curcumin decreased the
number of lung tumor nodules and inhibited lung metastasis of
melanoma. Therefore, it is possible to use curcumin in order to
arrest the metastatic growth of tumor cells.
A
study
conducted in 2014 revealed that curcumin was able to
obstruct tumor growth and metastasis in several animals’ organs
including the stomach, colon, and liver. Effect of
Curcumin on Lung Cancer |
Cancer stem cell-based treatments with curcumin could be proven
as potential processes and targets for tackling lung cancer (Ye
et al., 2012). Curcumin also seems to promote tumor progression,
reducing the efficiency of docetaxel in lung cancer patients.
The therapeutic effect of curcumin has also been exploited in
lung cancer. A mechanistic approach was used to study curcumin’s
anti-cancer potential, by targeting JAK2/STAT3 and NF-κB
signaling pathways, in the A549 lung cancer cell lin. In
addition, curcumin, via PI3K/Akt signaling suppression and
microRNA-192-5p up-regulation induced apoptosis in non-small
cell lung cancer cells with inhibition of cell proliferation.
In vivo curcumin lessens the migratory and invasive
capabilities of A549 cells and inhibited adiponectin expression
thought to be mediated through the NF-κB/MMP pathways and has
been proposed as an adjuvant in lung malignancy (Tsai et al.,
2015). Curcumin against human non-small cell lung cancer cell line
A549, which showed 50% cell viability at a high dose of 10,000 U
of interferon (IFN)-alpha (IFNα), was investigated to understand
the resistivity of these cells against such a higher
concentration of IFNα[64]. On treatment with one-tenth of the
IC50 value, the A549 cells showed an increase in p50 (NF-κB1)
and p65 (RelA) subunits of NF-κB with respect to time, in
addition to an increase in Cox-2 expression. On pretreatment
with curcumin, a dose-dependent decrease in these subunits was
noticed in Western Blot Analysis and a decrease in Cox-2
expression was also noted. Thus, curcumin showed a remarkable
decrease in NF-κB and Cox-2 activity in a dose-dependent manner
with a maximum dose of 50 μM in IFNα resistant A549 cell lines
and it increased the vulnerability of cells towards the
cytotoxic activity of IFNα. Animal
study revealed that curcumin administration reduced
ultra-histoarchitecture and histoarchitecture abnormalities
against benzo[a]pyrene induced lung carcinogenesis in mice (Wang
et al. 2016c). In in vitro studies, curcumin treatment is
reported to induce miR-98 and suppressed MMP-2 and MMP-9 which
leads to inhibition of lung cancer in A549 cell line (Liu et al.
2017). Curcumin downregulated the expression of hTERT, induced
cytotoxicity and attenuated proliferation in A549 cell line, and
suggested as effective target for lung cancer therapy
(Sadeghzadeh et al. 2017). Curcumin treatment reduced
CD133-positive cells, reduced the formation tumorsphere,
downregulated the expression of lung cancer stem cells markers
like Oct4, aldehyde dehydrogenase isoform 1A1, CD133, CD44 and
Nanog alongside induced apoptosis and inhibited proliferation of
lung cancer cells. In addition, it reduced lung cancer via
inhibition of sonic hedgehog and Wnt/b-catenin signaling
pathways (Zhu et al. 2017). Curcumin treatment inhibits
hepatocyte growth factor induced epithelial-mesenchymal
transition and angiogenesis by inhibiting PI3K/Akt/mTOR signal
transduction regulated by c-Met in human lung cancer cell line
A549 (Jiao et al. 2016). Recent evidence suggest that curcumin
treatment effectively prevented lung cancer metastasis and
growth by downregulating microRNA (miR)-let 7c and miR-101 mediated expression of enhancer of
zeste homolog 2 along with downregulation of Notch1 expression
in human lung cancer cell lines (A549 and NCI-H520) (Wu et al.
2016). Curcumin inhibited
IL-6-induced proliferation, migration, and invasiveness of human
small cell lung cancer (SCLC) cells by reducing JAK/STAT3
phosphorylation (i.e., activation) and downstream genes coding
for cyclin B1, survivin, Bcl-XL, MMPs, intercellular adhesion
molecule 1 (ICAM-1), and vascular endothelial growth factor
(VEGF). The therapeutic efficiency of curcumin in lung cancer is
exhibited by the suppression of COX-2, EGFR, NF-κB, and
PI3K/Akt signaling pathway. An interesting study by Jeeyun Lee
et al. investigated if interferon (IFN)-α stimulation activates
an NF-κB in lung cancer cells, and if curcumin annuls IFN-α
dependent NF-κB activation and subsequently NF-κB-regulated
gene's (cyclooxygenase-2's) expression. They reported that the
aforementioned hypothesis was correct in the case of A549 lung
cancer cells and curcumin effectively down-regulate COX-2
expression through IFN-α-dependent activation of NF-κB. G
Radhakrishna Pillai et al. reported that curcumin IC50 of 50 μM
is required to induce in vitro apoptosis in A549 cells [50].
Lichuan Wu et al. highlighted the fact that curcumin could
inhibit cell proliferation, colony formation, and tumorspheres
in lung cancer cell line NCI-H460. The underlying mechanisms of
curcumin-induced tumorspheres suppression are mainly due to the
inhibition of the JAK2/STAT3 signaling pathway. Furong Liu et
al. showed that curcumin exerts a cytotoxic effect on NSCLC A549
cells by inhibiting the PI3K/Akt/mTOR pathway to promote
apoptosis and autophagy. It indicates that PI3K/Akt/mTOR signal
transduction pathway is a key pathway involved in the role of
curcumin in lung cancer. One of the studies showed the effect of
curcumin on erlotinib-resistant non-small cell lung cancer
(NSCLC) cells. The combination of erlotinib and curcumin
reduced tumor growth remarkably in vivo in erlotinib-resistant
NSCLC cells. Ping Chen et al. provided the evidence that
gefitinib-resistant NSCLC cells growth could be inhibited by
downregulating Sp1/EGFR activity and the receptor tyrosine
kinase pathways with the use of curcumin and gefitinib together.
They also validated that curcumin could be utilized, in the
treatment of NSCLC with wild-type KRAS and EGFR mutation, as a
sensitizer of EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Effect of Curcumin on Breast Cancer | Curcumin
against resistant breast cancer have resulted in promising
results. The maximum
tolerable dose of curcumin was found to be 8 g/day.
During the pathogenesis of cancer,
multiple signaling pathways are involved and curcumin represents
a potential candidate for the regulation of these signaling
pathways. Among these, pro-inflammatory transcription factor
(NF-κB) is involved in breast cancer cell proliferation.
Curcumin down-regulates the NF-κB signaling pathway, thus,
affecting the cell proliferation and invasion contributing to
breast cancer treatment. In another breast cancer model,
curcumin induced autophagy through down-regulation of Akt
protein, posing a significant management strategy for breast
cancer. These findings suggest the therapeutic potential of
curcumin following multiple signaling pathways.
Adriamycin resistant MCF-7ADR and Tumor Necrosis Factor
resistant BT-20TNF breast cancer cell lines showed 15% (± 6%)
and 8% cell viability respectively against curcumin at a dose of
1 μg/ml (2.7 μM). The same study claimed that curcumin
exhibited the growth inhibitory effect on estrogen-dependent
MCF-7 and T-47D as well as estrogen-independent SK-BR3 cell
lines at lower concentrations, and arrested the majority of
cells in the G2/M phase and inhibition of ornithine
decarboxylase (ODC) activity. A comparative study of the effect
of curcumin on human mammary epithelial (MCF-10A) and MDR breast
carcinoma (MCF-7/TH) cell lines reported that the IC50 value of
curcumin against MCF-10A was 3.5 times higher than that of
MCF-7/TH although cytometric analysis showed equal accumulation
of curcumin in both cell lines and it is well complemented with
the apoptosis studies where 40 µM (24 hr) concentration of
curcumin led 1.8% of MCF-10A cells into apoptosis while 46.6% of
MDR, MCF-7/TH went into apoptosis under similar conditions,
which in terms of considering the collateral damages is a
significant observation. In an investigation undertaken by
Meiyanto et al., doxorubicin-resistant breast cancer cell lines
MCF-7/Dox cells with over-expression of HER2 were tested against
doxorubicin (IC50 = 7) and curcumin (IC50 = 80 ± 2.39)
separately and in combination. The MTT Assay showed that
curcumin at half of its IC50 concentration in combination with
doxorubicin at half of its IC50 concentration, decreased the
percentage cell viability of MCF-7/Dox cell lines by almost 80%,
and this synergistic action of combinatorial treatment-induced
cell death, evident through the accumulation of more cells in
sub-G1 and G1 phase as compared to the percentage of cells when
they were treated separately by doxorubicin and curcumin.
Efficacy of curcumin against resistant breast cancer cell lines
was demonstrated through SRB assay on MCF-7,
antiestrogen-resistant MCF-7/LCC2 and MCF-7/LCC9 cell lines,
which revealed IC50 values of curcumin to be 9.7, 12.2 µM and
11.34 µM respectively against these cancer cell lines and colony
formation for each cell line was suppressed by curcumin at a
concentration of 30 µM. These activities of curcumin were
attributed to lowering of anti-apoptotic expressions and
inhibition of NF-κB and Akt/mTOR pathway. The photosensitization
of cancer cells by curcumin towards photodynamic therapy (PDT)
has been covered by Muniyandi et al. and apoptosis is the mode
of action in majority of the works cited in the review. The
adriamycin resistant breast cancer cell line MCF-7/ADR was found
to be equally affected as MCF-7 cells (Cell viability 50%) on 45
minutes preincubation with curcumin (7.5 μM) followed by
irradiation with blue light (450 nm, 100 mW/cm2) for 5 min and
subsequent 24 h incubation. Clinical trial study
recommended that, administration of curcumin (6 g/day for seven
consecutive days in every 3 weeks) in combination with docetaxel
to be safe, effective and well tolerated for advanced and
metastatic breast cancer (Bayet-Robert et al. 2010). In vitro
models revealed that curcumin treatment is known to induce
cytotoxicity through apoptosis induction and inhibit the
viability of MCF-7 cells via caspase-3 and 9 activations. It
reduced the expression of miR-21 by upregulating the PTEN/Akt
signaling in breast cancer cells (Wang et al. 2017).
Experimental evidence suggested that curcumin administration
downregulate the expression of estrogen receptor-alfa (ER-a) and
tumor suppressor protein exerting antiproliferative effects in
T-47D human breast cancer cells (Hallman et al. 2017). Besides,
curcumin treatment reduced hypermethylation of glutathione
S-transferase (GST) pi 1 (Kumar, Sharma, and Rathi 2017) and
deleted in liver cancer 1 (DLC1) (Liu et al. 2017),
downregulated the Sp1 and DNA methyltransferase 1 expressions,
resulting in inhibition of proliferation of human breast cancer
cells (Liu et al. 2017). A recent study revealed that curcumin
treatment downregulated the expression of Fibronectin, Twist1
Vimentin, AXL, Slug, b-catenin, N-cadherin and E-cadherin
thereby inhibited the migration and invasion of cancer in breast
cancer cell lines (Gallardo and Calaf 2016). Curcumin inhibits
NF-jB signaling resulting in inhibition of cell growth and
invasion in MDA-MB-231 human breast cancer cell line (Yodkeeree
et al. 2010). Further, curcumin arrested the cell cycle at the
late S and G2M phase alongside induced ROS mediated apoptosis,
accumulated p16/Rb and P53/p21 in breast cancer cells (Calaf et
al. 2011; Wang et al. 2016d). In breast cancer cells, curcumin
prevented EMT-associated morphological changes induced by
lipopolysaccharide (LPS) while upregulating E-cadherin and
downregulating vimentin. It was further shown that curcumin
inhibited NF-κB/Snail signaling involved in LPS-induced EMT. In
another study, curcumin increased the expression of the small
non-coding RNA miR181b, which then downregulated proinflammatory
cytokines, CXCL1 and CXCL2, as well as MMPs, thereby reducing
the metastatic potential of breast cancer cells. Compelling
evidence has demonstrated the benefits of curcumin combination
therapy as compared to monotherapy in breast cancer. An in vitro
investigation reveals that the co-administration of curcumin and
4-hydroxytamoxifen (4-OHT), a metabolite of tamoxifen, could
restore the sensitivity of 4-OHT of HR-positive MCF-7 cells
through the downregulation of cyclin D1 and upregulation of p21.
Compared to either curcumin or 4-OHT alone, combined treatment
also remarkably activated pro-apoptotic protein Bcl-xL and
suppressed the Bcl-2 proteins, thereby further enhancing the
apoptotic activities. The phenomenon was reversed with the
combined treatment of curcumin and 4-OHT in MDA-MB-231 cells,
mediating cell death and preventing the metastatic behavior of
breast cancer cells, respectively. Co-treatment of curcumin (10
μg/mL) and trastuzumab (10 μg/mL) significantly reduced cell
proliferation and induced G2/M arrest in HER2-overexpressed
BT-474 and SK-BR-3-hr (a herceptin resistant strain from
SK-BR-3) breast cancer cells, compared to trastuzumab alone.
Further in vivo study revealed that BT-474 xenograft mice models
had the smallest tumor volume after 4 weeks of curcumin (45
mg/kg) and trastuzumab (4 mg/kg) co-treatment. Curcumin also
serves as a potential adjuvant with other chemotherapeutic
agents in augmenting anticancer effects. The combined treatment
of curcumin and paclitaxel significantly suppressed the
paclitaxel-mediated NF-κB expression and its regulatory genes
COX-2, matrix metallopeptidase 9 (MMP-9), VEGF, and
intercellular adhesion molecule 1 (ICAM-1), thus promoting the
anti-proliferative and anti-metastatic behavior in breast cancer
cells. Interestingly, further experiments proved that curcumin
and paclitaxel curbed the metastasis of MDA-MB-435 breast cancer
cells to lung tissues in xenograft mice models. More
importantly, this combination of curcumin (ranging from 25–225
mg/kg) and paclitaxel (5 mg/kg) was found to be safe and induced
no toxicity effects in mice models. Hindered by drug efflux and
chemoresistance, doxorubicin was explored in combination with
curcumin in breast cancer treatment. This has successfully
augmented the cytotoxicity effect on breast cancer cells Another
study illustrated that curcumin inhibited the
doxorubicin-induced EMT via the suppression of Akt, β-catenin
and glycogen synthase kinase 3 β (GSK3β) protein expression,
emphasizing the importance of the combined treatment of curcumin
and doxorubicin in inhibiting the metastasis of breast cancer
cells. Apart from the combination with chemotherapeutic agents,
the combined treatment of curcumin with other natural compounds
has also been investigated in breast cancer. Flow cytometry cell
death analysis showed that the co-treatment of curcumin (5 μM)
and berberine (25 μM) synergistically exerted apoptosis and
autophagy cell death to MDA-MB-231 and MCF7 breast cancer cells.
Moreover, curcumin (1.5 μM) sensitized the AU565 breast cancer
cells treated with quercetin (4 μM) and optiberry (2 μg/mL) to
decrease lapatinib-mediated HER2 overexpression via the
downregulation of HER2/Akt signalling pathways. Another study
reported the benefits of curcumin (200 mg/kg) and
epigallocatechin gallate (EGCG) (25 mg/kg) in lowering the tumor
burden of xenograft models via the reduction in phosphorylated
Akt, EGFR and vascular endothelial growth factor receptor-1
(VEGFR-1) expression, highlighting the enhanced anticancer
potential of this treatment regimen. Curcumin is believed to
show its impact on cell growth and invasion of breast cancer
partially through the down-regulation of NF-κB signaling
pathways. Curcumin induces p53-dependent apoptosis and also
causes cell cycle arrest in MCF-7 breast cancer cells. In
curcumin-treated MCF-7 cells, proapoptotic protein B-cell
lymphoma-2 (Bcl-2)-associated X protein (BAX) was found in a
high concentration and it indicates curcumin's p53-dependent as
well as p53-independent antiproliferative effects. Xiao-Dong Sun
et al. identified that curcumin could inhibit the
phosphorylation of extracellular regulated protein kinase
(ERK1/2) in MDA-MB-231 cells. ERK1/2 is a major signaling
molecule in the downstream pathway of EGFR. This is how curcumin
inhibits cell proliferation and induces cell apoptosis, by
inhibiting the EGFR pathway in vitro in MDA-MB-231 cells. Yunus
Akkoç et al. reported that in metastatic MCF-7 breast cancer
cells, overexpression of B-cell lymphoma-2 (Bcl-2) is a
constraining factor for curcumin-induced apoptosis. The
overexpression of Bcl-2 blocks curcumin-induced autophagy
through its inhibitory interaction with Beclin-1 in MCF-7 cells.
They found that pre-treatment with LY294002, a PI3K inhibitor,
enhanced curcumin-induced autophagy and apoptosis by modifying
Bcl-2 expression and subsequent autophagosome formation in MCF-7
breast cancer cells. In vivo effect of curcumin and its
derivative (2E,6E)-2,6-bis(4-hydroxy-3-methoxybenzylidene)cyclohexanone
(BHMC) had been checked on 4T1 (triple-negative breast cancer
cell line) breast cancer cells challenged mice. A study showed
that curcumin and BHMC treated mice had low tumor burden,
mitotic cells, lung metastasis as well as regeneration capacity
compared to the untreated mice.
Effect of Curcumin on Prostate Cancer
A randomized, double-blind, controlled study evaluated the
effects of soy isoflavones and curcumin on serum PSA levels in
men. The authors of this study concluded that curcumin
presumably synergizes with isoflavones to suppress PSA
production. Curcumin against resistant prostate cancer, the induction of
apoptosis has been one of the modes of action of curcumin.
PI3/Akt pathway, which promotes cell growth, proliferation, and
survival, is inhibited by curcumin. Mechanistic studies, carried
out at subtoxic concentrations of curcumin in LNCap cells showed
that pretreatment with curcumin sensitized the cells towards
tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
through inhibition of the NF-κB pathway of cell survival.
Castration-resistant prostate cancer cell (CRPC) line C4-2B,
showed a promising response to chemo-sensitization towards
remarkably low concentration dose of 10nM docetaxel on
pretreatment with a combination of 5 μM curcumin and 5 μM
nelfinavir, commendably without much adverse effect on primary
prostate epithelial cells. The molecular study revealed an
increase in pro-apoptotic markers caused by endoplasmic
reticulum (ER) stress and decrease in expressions associated
with PI3K/AKT survival pathway like phosphorylated-AKT. A summary of in vitro activities of curcumin against
various cancer cell lines has been compiled in Table 1. In a pilot phase II study, curcumin (6000 mg per day for 7
consecutive days) along with docetaxel and prednisone showed
therapeutic potential against castration-resistant prostate
cancer with good patient acceptability and tolerability
(Mahammedi et al. 2016). In vitro models revealed that,
curcumin treatment downregulated PGK1 via upregulation of
miR-143 alongside increased the expression of FOXD3, resulting
in inhibition of proliferation and migration of prostate cancer
cell (Cao et al. 2017). Curcumin treatment is known to induce
transferrin receptor protein 1 (TfR1) and iron regulatory
protein 1 (IRP1) expression which leads to induced autophagy and
apoptosis in castration-resistant prostate cancer cells (Yang et
al. 2017a). It has been reported that curcumin treatment
inhibited MT1-MMP and MMP-2 expressions in DU145 cells thus
reduced the metastasis and survival of prostate cancer cells
mediated by Notch-1 signaling cascade (Yang et al. 2017b).
Curcumin treatment induced the arrest of G0/G1 cell cycle phase
alongside inhibited the regulatory proteins cyclin D1 and CDK-2.
Besides, it upregulated the expression of p21, p27 and p53 while
downregulated Bcl-2 expression. Further, curcumin treatment is
known to activate caspase (3, 8 and 9) (Sha et al. 2016) while
decreased Akt, MMP (2 and 9), Bcl- 2, Bcl-XL and tumor volume in
prostate cancer (Jordan et al. 2016). Curcumin treatment is
reported to increase HDAC (1, 4 and 8), apoptosis, production of
ROS and Nrf- 2 expression, while decrease VEGF, HIF1-a, GSK-3b,
Akt, prostate-specific antigen (PSA) level, PSA mRNA expression,
HAT activity and cellular proliferation in LNCaP cell lines. The
available in vitro studies have shown that curcumin is able to
inhibit viability, proliferation, survival, migration/invasion,
and adhesion of various human prostate cancer cells. Curcumin
inhibited both androgen-sensitive and insensitive prostate
cancer cells by targeting a number of signaling cascades
responsible for regulating cellular function. The
antiproliferative, antisurvival, and antimigratory effects of
curcumin in prostate cancer cells may be due to the inhibition
of the Akt/mTOR, Ras/MAPK signaling pathways, decreased NF-κB
activation, enhanced proapoptoptic caspase and PARP cleavage,
and the inhibition of members of the antiapoptotic Bcl-2 family
of proteins. Curcumin was also able to induce cell-cycle arrest
and enhance autophagy in various prostate cancer cell lines. The
available in vivo studies have shown that curcumin
administration is able to inhibit the growth/volume, formation,
development, proliferation, and angiogenesis of prostate cancer
tumors while promoting apoptosis. These effects were observed in
mice xenografted with both androgen-sensitive and insensitive
prostate cancer cells. Curcumin’s inhibition of prostate tumor
growth and progression may be due to its inhibition of Akt
expression/activation, decreased NF-κB activation, inhibition of
the anti-apoptotic proteins Bcl-2 and Bcl-xL, increased
expression of the proapoptotic proteins Bax and Bak, and
enhanced PARP and caspase expression. These findings from in
vivo studies are in agreement with those from the in vitro
studies. The downregulation of cell proliferation, paired with
the enhanced activity of programmed cell death both in vitro and
in vivo, render curcumin an ideal candidate for the development
of novel anticancer pharmaceutical agents providing fewer
detrimental effects due to its low toxicity.
Androgendependent LNCaP
prostate cancer cells were injected subcutaneously into mice fed
with a 2% curcumin containing diet for up to 6 weeks. Curcumin
significantly increased the extent of apoptosis, as measured by
an in situ cell death assay, and caused a reduction in cell
proliferation, as measured by a BrdU incorporation assay.
Multiple studies have been done to evaluate the anticancer
effects of curcumin on androgen-sensitive as well as
androgen-resistant prostate cancer cell lines. T Dorai et al.,
2000, reported that curcumin can reduce the proliferation rate
to 20-30% compared to untreated LNCaP cells (androgen sensitive
prostate cancer cell-line). Asok Mukhopadhyay et al.
suggested that curcumin can cause tumor necrosis factor
(TNF)-induced apoptosis by suppressing NF-κB activation in the
prostate cancer cell. Similarly, curcumin also affects multiple
other proteins and pathways, such as c-Jun/activator protein 1
(AP-1), cyclin D1, CDK-4, phosphatidylinositol 3-kinase
(PI3K)/mechanistic target of rapamycin (mTOR)/E-twenty six
proto-oncogene 2 (ETS2) pathway to reduce proliferation, cell
growth in androgen-sensitive prostate cancer cell lines. Studies
have also shown the anticancer properties of curcumin on the
androgen-insensitive prostate cancer cell lines.
Curcumin-treated DU-145 prostate cancer cells showed reduced
expression of NF-κB in paired with less proliferation and
increased apoptosis. Curcumin additionally downregulated the
expression of nuclear transcription factor activator protein-1
(AP-1), composed of c-Fos and c-JUN. Many studies have analyzed
the effects of curcumin treatment in vivo on the mice
xenografted with various human prostate cancer cells. Thambi
Dorai et al., 2001, studied the effect of curcumin on athymic
nude mice implanted with LNCap cells. It showed a significant
increase in apoptosis and reduction in proliferation of LNCaP
cells demonstrated by the increased pycnotic brown staining
nuclei in situ. Effect of Curcumin on Colorectal Cancer
Curcumin has demonstrated potential against colorectal cancer
in numerous clinical trials. Curcumin could be used to
avoid colorectal cancer (CRC) in diabetics with type 2 diabetes
by lowering leptin blood levels and increasing adiponectin
levels. In a dose-escalation study
that explored the pharmacology of curcumin in humans, 15
patients with advanced colorectal cancer refractory to
standard chemotherapies consumed capsules compatible with
curcumin doses of between 0.45 and 3.6 g/day for up to 4 months.
Levels of curcumin and its metabolites in plasma, urine, and
feces were analyzed. Curcumin and its glucuronide and sulfate
metabolites were detected in plasma in the 10 nmol/L range and
in urine. A daily dose of 3.6 g of curcumin caused 62% and 57%
decrease in inducible prostaglandin E2 production in blood
samples taken 1 h after the dose was administered on days 1 and
29, respectively. A daily oral dose of 3.6 g of curcumin was
recommended for the phase II evaluation in the prevention or
treatment of cancers outside the gastrointestinal tract. In
another study, patients were given curcumin capsules at three
different doses (3.6, 1.8, and 0.45 g/day) for 7 days . The
recoveries of curcumin in normal and malignant colorectal
tissues of patients receiving 3.6 g of curcumin were 12.7 ± 5.7
and 7.7 ± 1.8 nmol/g, respectively. In addition, two metabolites
of curcumin, curcumin sulfate and curcumin glucuronide, were
identified in the tissue samples. Trace levels of curcumin were
found in the peripheral circulation. The levels of M1G were also
decreased by curcumin treatment in malignant colorectal tissue.
The study concluded that a daily dose of 3.6 g of curcumin is
pharmacologically efficacious in colorectal cancer patients. Curcumin against resistant
colorectal cancer studies on human colorectal cancer cell line
HCT116 and its isogenic 5-fluorouracil (5-FU) resistant cell
line HCT116R in a 3D model showed that curcumin potentiated the
anti-proliferative activity of 5-FU against these cell lines
through apoptosis and inhibition of formation of colonies, with
suppression of NF-κB pathway. This synergistic combination
increased the percentage of apoptotic cells by 56% in HCT116R
cell lines. The molecular role of curcumin in apoptosis has
already been shown in another report where it intensified the
downregulation of anti-apoptotic BclxL and cell division
favoring cyclin D1 protein caused by 5-FU in HCT116 and
HCT116+ch3 (Complemented with chromosome 3) cell lines and
inhibiting activation of IkBα kinase and its phosphorylation.
Chemo-sensitization of drug-resistant cancer cell lines by
curcumin, towards a particular chemotherapeutic agent, has been
reported in one more investigation involving oxaliplatin
sensitive human colorectal adenocarcinoma HT29 Cells and its
oxaliplatin resistant derived sub-line HTOXAR3 cells, which
showed that combination of curcumin and oxaliplatin almost
reversed the oxaliplatin resistance. Clinically, curcumin
administration (3 g/day orally for one month) converted advanced
colon cancer derived regulatory T cells to T helper 1 cells via
increasing IFN-c production and repression of Foxp3 expression in
colon cancer patients (Xu, Yu, and Zhao 2017). In a
nonrandomized, open-label clinical trial, oral curcumin (2 g or
4 g per day for 30 days) administration reduced the number of
aberrant crypt foci and prevented the colorectal neoplasia
(Kunnumakkara et al. 2017; Carroll et al. 2011). In vitro models
revealed that treatment with curcumin induced apoptosis,
arrested the cell cycle at the G1 phase, decreased the cell
population as well as inhibited the proliferation and mutation
of COLO 320DM cells (Dasiram et al. 2017). Additionally,
curcumin treatment stimulated 50AMP-activated protein kinase,
suppressed the phosphorylation of p65 NF-jB, downregulated
MMP-9 and urokinase-type plasminogen activator (uPA) expression
as well as reduced the binding ability of NF-jB DNA in LoVo and
SW480 cells leading to inhibition of colon cancer invasion (Tong
et al. 2016). Curcumin treatment downregulated chemokine
receptor 4 expression, upregulated naked cuticle homolog 2
expression and suppressed Wnt signaling. In addition, curcumin
treatment downregulated vimentin and upregulated E-cadherin
expression, which leads to inhibition of proliferation and
epithelial mesenchymal transition in SW620 human colon cancer
cells (Zhang et al. 2016d). Evidence suggested that curcumin
treatment downregulated the expression of p-glycoprotein
(Neerati, Sudhakar, and Kanwar 2013) and upregulated
PPAR-c protein (Liu et al. 2015), the potential mechanism by
which curcumin can be used for the treatment of colon cancer
(Neerati, Sudhakar, and Kanwar 2013). In a 30-day study in 44
men with lesions in the colon that sometimes turn cancerous, 4
grams of curcumin per day reduced the number of lesions by 40%.
In a nonrandomized, open-label clinical trial in smokers,
curcumin reduced the formation of aberrant crypt foci (ACF), the
precursor of colorectal polyps. Curcumin at 4 g/day
significantly reduced ACF formation. The reduction in ACF
formation by curcumin was associated with a significant fivefold
increase in post-treatment plasma curcumin/conjugate levels.
Curcumin was well-tolerated at both concentrations. These
findings demonstrated the effect of curcumin against ACF
formation in smokers. A study published in the International
Journal of Cancer found that curcumin compares favorably with
oxaliplatin as an antiproliferative agent in colorectal cell
lines. A study showed a profound reduction in the incidence of
colorectal carcinoma when curcumin is introduced. In another
recent study, curcumin was administered to patients with
colorectal cancer after diagnosis and before surgery. Curcumin
was given three times a day for 10–30
days. Curcumin administration decreased
serum TNF-α level, increased the number of apoptotic cells, and
enhanced the expression of p53 in tumor tissue. The authors of
this study concluded that curcumin treatment can improve the
general health of colorectal cancer patients via the mechanism
of increased p53 expression in tumor cells. In summary, the
studies discussed in this section suggest curcumin’s safety and
efficacy in patients with colorectal cancer.
Effect
of Curcumin on Pancreatic Cancer
| A single-blind, randomized,
placebo-controlled study from India was conducted to evaluate
the effects of oral curcumin with piperine on the pain and
markers associated with oxidative stress in patients with
tropical pancreatitis. Twenty patients with tropical
pancreatitis were randomly assigned to receive 500 mg of
curcumin with 5 mg of piperine or to receive placebo for 6
weeks, and the effects on the pattern of pain and on red blood
cell (RBC) levels of MDA and GSH were assessed. The results
indicated a significant reduction in the erythrocyte MDA levels
compared with placebo after curcumin therapy, with a significant
increase in GSH levels. The authors of this study concluded that
oral curcumin with piperine may reverse lipid peroxidation in
patients with tropical pancreatitis. Curcumin was found safe and
well-tolerated in a phase II clinical trial of patients with
advanced pancreatic cancer. Of the 25 patients enrolled in the
study, 21 were evaluable for response. Patients were given 8
grams of curcumin per day orally until disease progression, with
restaging every 2 months. No toxicities associated with curcumin
administration were noted in the patients. A downregulation in
the expression of NF–κB, COX-2, and pSTAT3 in peripheral blood
mononuclear cells of patients was observed after curcumin
intake. There was considerable interpatient variation in plasma
curcumin levels, and drug levels peaked at 22 to 41 ng/ml and
remained relatively constant over the first 4 weeks. The study
concluded that the oral curcumin is well-tolerated and, despite
limited absorption, has biological activity in some patients
with pancreatic cancer. An open-label phase II trial evaluated
the efficacy of curcumin in combination with gemcitabine against
advanced pancreatic cancer. Kanai et al. recently evaluated the
safety and feasibility of combinations of curcumin and
gemcitabine in 21 patients with gemcitabine-resistant pancreatic
cancer. Curcumin at 8 g/day in combination with gemcitabine was
safe and well-tolerated. Effect of Curcumin on Bladder
Cancer
| In animal model, curcumin suppressed the invasion and growth
of bladder cancer via induction of apoptosis and arresting G1/S
phase transition in N-methyl-N-nitrosourea induced bladder tumor
in rats (Pan et al. 2017). Curcumin treatment suppressed the
N-methyl-N-nitrosourea-induced urothelial tumor in rats. In cell
lines studies, curcumin treatment is known to downregulate the
expression of insulin-like growth factor (IGF)-2 and reduces the
IGF1R and IRS-1 phosphorylation in T24 and UMUC2 bladder cancer
cells. In this regards curcumin functions through suppression of
IGF-2-mediated PI3K/AKT/mTOR signal transduction (Tian et al.
2017). Curcumin treatment reversed the transition of
epithelial-mesenchymal cells via reducing ERK5/AP-1 signaling
pathway in SV-40 human urothelial cells which might be the
potential drug candidate for prevention of bladder cancer (Liu
et al. 2017). In human bladder cancer cell lines, curcumin
treatment exert multiple effects like inhibition of MMP-2/9,
generation of ROS, upregulated the expression of HO-1, increased
the hypomethylation of the miR-203, upregulated the expression
of miR-203, inhibited Aurora A promoter activity, downregulated
histone H3 activation, induced G2/M phase cell cycle arrest,
decreased the expression of cyclin D1 and COX-2, decreased VEGF
level, decreased c-myc, decreased Bcl-2 expression,
downregulated Survivin protein, upregulated the expression of
p53 and Bax, induced fragmentation of DNA, downregulated cyclin
A expression and decreased NF-kB expression thereby inhibited
the cancer cell invasion, viability of cancerous cells and
growth (Imran et al. 2016; Saini et al. 2011).
Effect of Curcumin on
Blood Cancer (Multiple Myeloma and Leukemia), Lymphoma, and
other Hematological Malignancies
Curcumin against resistant leukemia showed inhibition in
growth and clonogenicity to curcumin treatment in dose and
time-dependent manner. Golombick et al. conducted a
single-blind, crossover pilot study to determine the effects of
curcumin on plasma cells and osteoclasts in patients with MGUS.
Curcumin decreased the paraprotein load in the ten patients with
paraprotein >20 g/L, and five of these ten had a 12% to 30%
reduction in paraprotein levels while receiving curcumin
therapy. In addition, 27% of patients receiving curcumin had a
>25% decrease in urinary N-telopeptide of type I collagen. The
study suggested the therapeutic potential of curcumin against
MGUS. Vadhan-Raj et al. evaluated the safety, tolerability, and
clinical efficacy of curcumin in 29 patients with asymptomatic,
relapsed, or plateau phase multiple myeloma. Curcumin was given
either alone (orally at 2, 4, 6, 8, or 12 g/day in two divided
doses) or in combination with piperine (10 mg in two divided
doses) for 12 weeks. Curcumin and piperine were well-tolerated,
with no significant adverse events. Furthermore, oral
administration of curcumin was associated with significant
downregulation in the constitutive activation of NF–κB and
STAT3, and it suppressed COX-2 expression in most of the
patients. These observations suggest the potential of curcumin
against multiple myeloma. In another study, curcumin showed an
IC50 value of 35.7 µM against KG1a 23.5 µM against Kasumi-1 on
96 hr exposure and completely stopped colony formation at 20 µM
concentration. The mechanistic investigations reflected the role
of curcumin in activation of Caspase-3, down-regulation of Bcl-2
mRNA expression and reduction in mitochondrial membrane
potential in addition to remarkable morphological changes like
cell shrinking and nuclear condensation, which are
characteristics of apoptosis. Another drug-resistant leukemia
cell line HL60 responded to curcumin with 50% growth inhibition
at 30 µM concentration. Cell cycle studies in this experiment
established apoptosis as the mechanism of action of curcumin and
arrest of the cell cycle in the S-phase was also reported in the
same study. Clinically, curcumin administration (5 g for 6
weeks) possessed potent chemosensitizing effect in chronic
myeloid leukemia patients, where the patients receiving both
curcumin and imatinib exhibited better prognosis with decreased
NO levels as compare to the patients receiving imatinib alone
(Ghalaut et al. 2012). In animal study, curcumin treatment
significantly decreased tumor growth in the chronic myeloid
leukemia xenograft mice via release of exosomes enriched miR-21
in plasma (Taverna et al. 2015). In cell line studies, curcumin
treatment upregulated apoptosis inducing factor, caspase-3,
cleaved PARP-1 while downregulated Bcl-2 resulting in induction
of apoptosis in lymphoblastic leukemia cells (Mishra, Singh, and
Narayan 2016). Curcumin incubation (10 lM, for 6 days) increased
the level of ROS, induced genomic instability, mediated reversal
of p15 promoter methylation and induced apoptosis in Raji cells
(Sharma et al. 2014). Curcumin treatment (40 mmol/L, for 48h)
downregulated the protein expression of nuclear NF- jB P65 as
well and its translocation alongside inhibited proliferation
of acute myeloid leukemia in KG1a and Kasumi-1 cells (Rao et al.
2015). Also, curcumin treatment (25 lM, for 24–48 h) arrested
cell cycle in the S-phase, increased the number of annexin
V-FITC(þ)/PI(-) cells and inhibited the proliferation of SHI-1
cells. In addition, curcumin upregulated FasL and downregulated
NF-jB, ERK, Bcl-2, MMP-2 and MMP-9 expressions. Further,
curcumin induced the activation of MAPK, p38, caspase-3 and JNK
resulted in inhibition of SHI-1 cell invasion (Zhu et al. 2016).
Curcumin treatment downregulated the expression of VEGF and
decreased the phosphorylation of AKT. Curcumin mediated
increased miR-196b levels caused downregulation of Bcr-Abl
expression in chronic myelogenous leukemia cells (Taverna et al.
2015). Curcumin incubation downregulated Mcl-1 expression and
associated with apoptosis in human myeloma cell lines
(Gomez-Bougie et al. 2015). Curcumin treatment simultaneously
inhibited RAF/MEK/ERK and AKT/mTOR pathway activation resulting
in induction of apoptosis and inhibition of proliferation in
human leukemia THP-1 cells (Guo et al. 2014). Curcumin
incubation increased the generation of intracellular ROS,
depletion of intracellular GSH, and activation of caspase
enzyme. Chu-Wen Yang et al. investigated the effect and mode of
action of curcumin on monocytic leukemia THP-1 cells, derived
from human acute monocytic leukemia. The authors demonstrated
that curcumin-induced THP-1 cell apoptosis through the
activation of c-Jun NH2-terminal kinase/extracellular
signal-regulated kinase/activator protein 1 (JNK/ERK/AP1)
pathways. Yi-Rong Chen et al. reported that curcumin affects the
mitogen-activated protein kinase kinase kinase 1/JNK
pathway by interfering with the signaling molecules like AP-1
and NF-κB as a possible mechanism of action. They speculated
that curcumin may affect the JNK pathway by interfering with the
signaling molecules at the same level or proximally upstream of
the MAPK kinase kinases (MAPKKKs) level. Yaowu Zhang et al.
showed curcumin can induce apoptosis in osteosarcoma MG63 cells
through the mitochondrial pathway. They reported that the
effects of curcumin-induced apoptosis in osteosarcoma cells were
associated with caspase-3 activation and reduced the levels of
Bcl-2 expression. Jia Rao et al. reported a similar function of
curcumin in AML cells. They showed that curcumin down-regulates
Bcl-2 and induces apoptosis in daunorubicin (DNR)-insensitive
CD34+ AML cell lines and primary CD34+ AML cells. Seong-Su Han
et al. reported that curcumin inhibited the proliferation of
BKS-2, an immature B cell lymphoma, more effectively than that
of normal B lymphocytes and caused the apoptosis of BKS-2 cells
in a dose- and time-dependent manner. The authors concluded that
curcumin downregulated the expression of survival genes early
growth response 1 (EGR-1), cellular myelocytomatosis (c-myc),
and Bcl-extra large (Bcl-XL) as well as the tumor suppressor
gene p53 in B cells as its possible mechanism of action. Shilpa
Kuttikrishnan et al. investigated the anticancer potential of
curcumin in acute lymphoblastic leukemia. The authors concluded
that curcumin suppresses B-pre-ALL cells' growth and
proliferation by inactivation of the PI3K/Akt signaling pathway.
Guo-Hua Zhu et al. reported that curcumin significantly induces
apoptosis but also partially suppresses invasion in SHI-1 cells
(acute monocytic leukemia cell line) in vitro. Their results
from polymerase chain reaction (PCR) and western blotting showed
that curcumin increased the FasL mRNA level; inhibited Bcl-2,
NF-κB, and ERK expression; and activated p38 MAPKs, JNKs, and
caspase-3. Zai-Xin Li et al. studied how curcumin affects the
proliferation of the Raji cells of Burkitt's lymphoma. Their
biochemical studies showed that cell apoptosis increases through
upregulation of Bid (BH3-interacting domain death agonist),
cytochrome C, and BAX, while oncogene c-Myc was downregulated
after curcumin treatment. Taken together, their results
suggested that mitochondrial damage induction was the main
mechanism of action of curcumin which led to apoptosis of the
Raji cells. In vivo effects of curcumin in the xenograft mouse
model showed its effective inhibition of tumor growth. All in
all, these results were suggestive of curcumin's growth
suppressing effect on Burkitt's lymphoma cells both in vivo and
in vitro system. Effect of Curcumin on Cervical Cancer | Curcumin
administration (12,000 mg/day for 3 months) reduced the risk of
cervical cancer and is found to be safe and well tolerated
chemotherapeutic in phase I clinical trial (Cheng et al. 2001).
In animal model, curcumin suppressed nuclear b-catenin,
decreased oncogenic miRNA-21 and abrogated E6/E7 HPV expression
in orthotopic mouse model of cervical cancer (Zaman et al.
2016). Curcumin administration (1000 or 1500 mg/kg, for 30 days)
significantly downregulated the expression of VEGF, COX-2, EGF-R
and inhibited angiogenesis and tumor growth in cervical cancer
xenografts model of nude mice (Yoysungnoen-Chintana,
Bhattarakosol, and Patumraj 2014). In cell line studies,
curcumin treatment (13 mM) upregulated the expression of
early-onset breast cancer 1, O6- methylguanine-DNA
methyltransferase, mediator of DNA damage checkpoint 1,
p-H2A.XSer140 and p-p53 as well as induced translocation of
p-H2A.XSer140 and p-p53 from cytosol to nuclei, resulting in
chromatin condensation and induction of DNA damage in HeLa human
cervical cancer cells (Shang et al. 2016a). Curcumin activated
ATF6, PERK, IRE-1aand elevated the levels of ROS intracellularly
as well as induced apoptosis and inhibited the proliferation of
cervical cancer cells (ME180, C33A, HeLa and CaSki) (Kim et al.
2016a). Curcumin counteracts estradiol induced proliferation of
cervical cancer via induction of apoptosis in cervical cancer
cells (Singh and Singh 2011). Incubation with curcumin (20 mM,
for 72 h) reversed the hypermethylation and reactivation of the
RARb2 gene in cervical cancer cell lines (Jha et al. 2010).
Curcumin (50 or 100 mM, 24 h) dose dependently reduced the
phosphorylation of ERK, increased the activity of caspase 3 and
caspase 9, upregulated AIF, Bax, cytochrome while downregulated
Bcl-XL, Bcl-2 in cervical cancer cells. Curcumin treatment
downregulated the expression of cyclin D1, iNOS and COX-2 in
HeLa, SiHa and Ca Ski cells, and acts as an anti-proliferative
agent (Singh and Singh 2009). Effect of Curcumin on Thyroid
Cancer
| In cell line studies, curcumin treatment upregulated
E-cadherin while downregulated vimentin and MMPs expressions
along with reduced metastasis, cell spreading and cell migration
in human papillary thyroid carcinoma cells. Curcumin suppressed
TGF-b1 mediated transcription, activation and secretion of
matrix metalloproteinases. It also inhibited TGF-b1 induced
Smad2 and Smad3 phosphorylation in human papillary thyroid
carcinoma BCPAP cells (Zhang et al. 2016a). Curcumin treatment
induced DNA damage in thyroid carcinoma BCPAP cells via
upregulation of H2A.X phosphorylation at Ser139 and ATM-mediated
activation of Chk2-Cdc25C-Cdc2 pathway. Moreover, curcumin
induced caspase mediated apoptosis in BCPAP cells (Zhang et al.
2016b). Curcumin downregulated the expression of HIF-1aand its
binding to hypoxia response element in K1 papillary thyroid
cancer cells. In addition, curcumin upregulated the expression
of E-cadherin, inhibited the activity of MMP-9 (Zhang et al.
2013a) and weakened K1 cells migration resulting in
anti-metastatic effect (Tan et al. 2015). Curcumin treatment
reduced the phosphorylation of PI3K and Akt pathway, and
downregulated the expression of MMP-1/7 and COX-2 leading to
inhibition of cell migration, growth and invasion of thyroid
cancer cells (FTC133) (Xu, Qin, and Liu 2014). Curcumin
instigate the production of ROS, reduce mitochondrial membrane
potential and altered intracellular calcium concentration
thereby mediate apoptotic induction in papillary thyroid cancer
cell line K1 (Song et al. 2012). Effect of Curcumin
on Skin Cancer
| Curcumin
decreased the phosphorylation of IRS-1, ILGF-1 receptor, Akt,
4EBP1 and S6K in the mouse keratinocyte cells alongside exerted
significant anticancer activity against
7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl
phorbol-13-acetate induced skin cancer in mice (Kim et al.
2014). In in vitro studies, curcumin treatment is reported to
upregulate mmu-miR-205-5p expression, block proliferating cell
nuclear antigen, downregulate Bcl-2 expression and sup- press
JAK-2/STAT3 pathway which in turn induction of apoptosis and
inhibition of proliferation and invasion (Lelli, Pedone, and
Sahebkar 2017). Curcumin treatment arrested the G2/M phase of
cell cycle as well as induced autophagy in human melanoma cells
(A375 and C8161). In addition, curcumin reduced the activation
of P70S6K, and downregulated AKT and mTOR expressions which
might offer plausible target in the treatment of human melanoma
(Zhao et al. 2016a). In another study, curcumin decreased the
invasion of squamous cell carcinoma by suppressing STAT3
signaling pathway in A431 cells (Wu, Lu, and Cui 2015). Curcumin
induced the opening of mitochondrial permeability transition
pore and melanoma cell death in WM-115 melanoma cells (Qiu et
al. 2014). Curcumin inhibited NF-jB pro-survival pathway,
upregulated the p53 tumor suppressor protein and downregulated
Bcl-2 expression resulting in apoptosis and reversal of skin
cancer (Chinembiri et al. 2014). Effect of Curcumin
on Brain Cancer
| Curcumin was shown to
have inhibitory effects on telomerase and induced telomere
shortening and apoptosis in brain tumor cells. Curcumin induced
growth inhibition and cell cycle arrest at G2/M in
medulloblastoma and glioblastoma cells. In various types of
cancers, curcumin was shown to selectively target cells that
express telomerase enzyme making these cells more vulnerable to
curcumin-induced cytotoxicity of cancer cells. Importantly, the
above-mentioned study revealed that the complex and diverse
action of curcumin, and its efficacy could depend on the cell
types used. The long-term studies on brain tumor cells
highlighted the use of curcumin as an adjuvant for cancer
therapy. Telomere shortening drives renal cell senescence and
leads to renal aging. Khaw and co-workers have demonstrated that
curcumin suppresses telomerase activity in brain tumor cells
which is associated with reduction in hTERT levels. Treatment
with curcumin induces a significant telomere shortening in brain
tumor cells suggesting its potential clinical application as
telomerase inhibitor and use of curcumin in adjuvant cancer
therapy. By contrast, in normal cells curcumin improves
viability by acting on telomerase when the cells have been
stimulated with toxic molecules. A study conducted on SK-N-SH
cells treated with curcumin improved cell viability. Normally,
hTERT was inhibited by Aβ1–42; shortened telomere could not
restore length, and then, there were plenty of apoptotic cells.
Treatment with curcumin could bind to Aβ1–42 and antagonize
neurotoxicity; thus, the expression of hTERT was upregulated,
shortened telomere restored length and the numbers of cells were
increased. Long-term studies on brain tumor cells underscore the
use of curcumin in adjuvant cancer therapy. Curcumin against brain cancer in vivo model of Human
glioma U-87 cells in athymic mice on intraperitoneal dose of
curcumin (120 mg/kg/day) showed less than 50% decrease in median
tumor volume in subcutaneous xenograft while in the orthotopic
model, the average life span of group receiving similar dose
increased by 12% as compared to the control group. In Female
SCID mice xenograft model, human primary medulloblastoma cells
(DAOY) were subcutaneously injected and after 30 days, the
animals were given oral gavage of curcumin (1 mg/kg) dissolved
in corn oil. The tumor growth inhibition in curcumin treated
group was significantly noticeable as compared to the control
group. The group of Smo/Smo transgenic medulloblastoma mice
receiving oral dose of curcumin was reported to have a median
survival time of 192 days as compared to the control group,
which had a median survival time of 144 days. This observation
is in agreement with earlier claims of ability of curcumin to
cross Blood Brain Barrier. Mechanistic insights in xenografted
human medulloblastom D425 cells in athymic mice showed
overexpression of p65 subunit of NF-κB and the curcumin treated
group showed tumor growth inhibition which can be partially
attributed to down regulation of p65 subunit. In another in vivo
investigation, human glioblastoma U87-MG cells-inoculated nude
mice were administered with 100 mg/kg per day of curcumin in
DMSO in Phosphate Buffer Saline through intra-tumoral
injections. After seven days, significant decrease in tumor size
was observed in curcumin treated group. Microscopic examination
post Acridine Orange staining showed increased acidic vesicular
organelles in curcumin treated cells with intact nuclei,
pointing towards curcumin-induced autophagy being responsible
for cell deaths. Effect of Curcumin on Medulloblastoma and Neuroblastoma
Medulloblastoma is the common malignant brain tumor in
pediatrics. In animal model, curcumin inhibited tumor growth and
increased the survival rate in Smo/Smo transgenic
medulloblastoma mice (Lee et al. 2011). In cell line studies,
curcumin treatment arrested G2/M phase of cell-cycle, activated
GSK-3band suppressed Wnt/b-catenin path- way resulting in
inhibition of proliferation in DAOY medul- loblastoma cell line
(He et al. 2014). Curcumin treatment upregulated the PTEN gene
expression and downregulated the expression of E2F1, CDK2 and
cyclin E1 gene resulting in growth arrest at G2/M phase in
medulloblastoma cells. In addition, curcumin treatment increased
caspase-3/7 activity, overexpressed Bax while downregulated
Bcl-2, Bcl-Xl and surviving expression, which leads induced
apoptosis of human medulloblastoma cells (Bangaru et al. 2010).
Curcumin treatment inhibits telomerase activity and gene
expression of hTERT resulting in telomere shortening in
medulloblastoma cell lines (A172, KNS60, U251MG and ONS76) (Khaw
et al. 2013). Curcumin phosphorylates Cdc27, a component of the
anaphase promoting complex/ cyclosome, which is known to
ubiquitinate securing and cyclin B, resulting in proteolysis and
apoptosis of DAOY medulloblastoma cell (Lee and Langhans 2012).
Further, it was reported that, curcumin treatment induced
apoptosis and cell cycle arrest possibly through downregulation
his- tone deacetylase 4 and enhanced tubulin acetylation.
Curcumin treatment inhibited the sonic hedgehog-glioma
associated oncogene-1 pathway via downregulating the protein
expression of sonic hedgehog ligand, and its most important
downstream targets glioma associated oncogene-1 and patched-1
receptor. Furthermore, curcumin reduced the levels of b-catenin,
N-myc, C-myc, cyclin D1 and induced apoptosis in DAOY
medulloblastoma cells (Elamin et al. 2010). Effect of
Curcumin on Ovarian
Cancer | Curcumin exhibits the important anti-cancer
activity in ovarian cancer via the pro-apoptotic function.
Curcumin inhibited ovarian cancer cell proliferation and
promoted apoptosis, and first confirmed it was associated with
the regulatory network of circ-PLEKHM3/miR-320a/SMG1. Liu et al.
reported that curcumin could constrain ovarian cancer cell
proliferation and facilitate apoptosis by inhibiting autophagy
and AKT/mTOR/p70S6 pathway. Yen et al. suggested that curcumin
could suppress ovarian cancer cell colony formation via blocking
the Wnt/β-catenin pathway. These reports indicated the
anti-cancer property of curcumin in ovarian cancer treatment. In
the past research, curcumin had been found to improve the
radiosensitization of nasopharyngeal carcinoma through
regulating the circRNA network. Xu et al. suggested that
curcumin could suppress non-small cell lung cancer progression
by regulating circ-PRKCA. Circ-PLEKHM3 was downregulated in
ovarian cancer, and its expression could be promoted by
curcumin. Function analysis showed that circ-PLEKHM3
overexpression could aggravate curcumin function by suppressing
cell proliferation, triggering apoptosis and reducing
tumorigenesis in ovarian cancer. These data revealed that
curcumin might regulate ovarian cancer progression by promoting
circ-PLEKHM3. In addition, the anti-cancer role of circ-PLEKHM3
was confirmed in study, which was consistent with the previous
study. A previous report displayed the circ-PLEKHM3 acted as
miR-9 sponge to regulate ovarian cancer progression. MiR-320a
mimic reversed the regulation of circ-PLEKHM3 on
curcumin-mediated ovarian cancer cell proliferation and
apoptosis, further confirming that circ-PLEKHM3 sponged miR-320a
to participate in ovarian cancer progression. The study also
validated the carcinogenic role of miR-320a in ovarian cancer,
which was consistent with previous reports. These data indicated
the importance of circ-PLEKHM3/miR-320a axis for curcumin in
ovarian cancer development. Curcumin could up-regulate SMG1
expression via modulating circ-PLEKHM3/miR-320a axis. Curcumin
could suppress proliferation and promote apoptosis in ovarian
cancer, possibly via regulating circ-PLEKHM3/miR-320a/SMG1 axis.
This research might propose a novel mechanism for understanding
the function of curcumin in ovarian cancer. Effect of
Curcumin on Liver Cancer | Yu and his colleagues
evaluated the role of curcumin in inhibiting the human hepatoma
SMMC-7721 cells significantly by promoting apoptosis via
modulation of Bax/bcl-2 (Yu et al., 2011). Apoptosis was
associated with increases in p53 levels as well as its
DNA-binding ability, along with protein expression of Bax.
Phosphorylation of CDC27 (cell division cycle 27) is the main
mechanism of anticancer efficacy of curcumin by obstructing cell
growth and proliferation in an apoptotic pathway, leading to the
death of the cells (Lee and Langhans, 2012). According to Li and
his colleagues, in human hepatoma cell lines such as HepG2 and
HCCLM3, suppression of miR-21 improved anticancer action of
curcumin like cell growth suppression, apoptosis via upregulated
target gene, and TIMP3 expression, and the mechanism may refer
to TGF-β1/smad3 signaling pathway inhibition (Li J. et al.,
2020). Curcumin inhibits cancer through modulating several
signaling pathways and molecular targets, including
TGF-β1/smad3, IGF, PI3K/Akt, Wnt/β-catenin, and vascular
endothelial growth fact (VEGF) (Figure 7) (Mohebbati et al.,
2017). Effect of
Curcumin on Other
Cancer | Curcumin treatment significantly inhibited gastric
carcinoma. Curcumin therapy of Burkitt’s lymphoma cell lines in
combination with ionizing radiation shows that it boosts
lymphoma cells’ susceptibility to ionizing radiation-induced
apoptosis and improves cell cycle arrest at the G2/M phase.
Curcumin and L-ASP show synergism in patients with blood and
bone marrow malignancy (Jiang et al., 2015). Curcumin also
hinders the cellular growth of uterine leiomyosarcoma and
reduces the spread of castrate-resistant disease and human
leiomyosarcoma cells via modulating the AKT-mammalian target of
rapamycin pathway for inhibition (Wong et al., 2011). Curcumin
extract’s potential in decreasing tumors induced chemically was
investigated. It was documented that curcumin is useful in
reducing papilloma development throughout carcinogenesis and
progression. Dietary curcumin can reduce the number of papilloma
that promoted skin tumor, which was explored by Limtrakul et al.
(2001) as ras-p21 and fos-p62 oncogene expression was decreased
dose-dependently by curcumin. In addition, curcumin prevents the proliferation of
uterine leiomyosarcoma via induction of apoptosis, autophagy,
ERK 1/2 activity and fragmentation of DNA in gastric carcinoma
cells (Imran et al. 2016). Curcumin treatment suppressed
JAK-STAT signaling thus reducing tumor cell growth in ovarian
(OVCA 420 and OVCA 429) and endometrial (RL95-2 and Ishikawa)
cancer cell lines (Saydmohammed, Joseph, and Syed 2010).
Curcumin down-regulated the expression of IL-6, IL-11 and NF-kB
which leads to induce apoptosis of fibrosarcoma cells resulting
in anticancer activity against bone cancer (Kondo et al. 2001;
Kwak et al. 2006). Curcumin induced cell cycle arrest in G2/ M
phase, apoptosis and cytotoxicity in squamous carcinoma cells as
well as reduced tumor volume in head and neck cancer (Borges et
al. 2017). Curcumin treatment reversed the migration and
proliferation of hepatic carcinoma by downregulating the
expression of HIF-1a. In addition, curcumin reduced the level of
MMP-2 and MMP-9 as well as decreased the phosphorylation of p38,
which is associated with suppression of cancer invasion and
migration in hepatic carcinoma. Additionally, curcumin
treatment exhibited anti-proliferative effect in MHCC97H liver
cancer cells through generation of ROS, apoptosis and activating
toll like receptor -4/MyD-88 pathway (Imran et al. 2016; Liang
et al. 2014). Curcumin treatment significantly upregulated the
expression of p21/CIP1 and p27/KIP1 CDK, and downregulated the
expression of cyclin D1 resulting in decreased proliferation of
pancreatic cancer cells. Apart from this, curcumin induced
apoptosis via downregulating the ratio of Bcl-2/Bax and
increasing the activation of caspase-9/3 in pancreatic cancer
cells. Curcumin treatment inhibited PI3K/ Akt pathway and
induced forkhead box O1 in Panc-1 pancreatic cancer cells
leading to apoptosis (Zhao et al. 2015). Curcumin suppressed the
oral tumor volume, numbers of dysplasic lesions, papillomas and
squamous cell carcinoma (Imran et al. 2016). Interestingly,
curcumin treatment has potential for many cancer types like
esophagus cancer, testicular cancer, sarcoma and lymphoma
(Kunnumakkara et al. 2017). Curcumin has been reported to have
pharmacological efficiency towards multiple other cancer types
like gastric, colorectal, liver, and osteosarcoma. Xiang Zhou et
al. reported that curcumin, in combination with oxaliplatin and
5-fluorouracil (5-FU), exhibited synergistic inhibitory effect
in xenograft gastric tumor (BGC-823 cancer cells) via
downregulation of Bcl-2 and cleavage of caspase-3 and PARP
through upregulation of BAX [81]. Gizem Calibasi-Kocal et al.
reported the dose-dependent chemopreventive role of curcumin in
HCT-116 and LoVo cells (human colon cancer cell lines) possibly
through inhibition of NF-κB and/or activation of caspase-3 and
caspase-9. Biqiong Ren et al. demonstrated the antiproliferative
role of curcumin on liver cancer and reported its mechanism of
action through inhibition of the heat shock protein 70-toll like
receptor 4 (HSP70-TLR4) signaling pathway. Duk Su Lee DS et al.
demonstrated curcumin-induced p53 upregulation, cell cycle
arrest at gap-1/synthesis (G1/S) and G2/S phase, and caspase-3
activation in human osteosarcoma cells. Curcumin has been
reported to possess antiproliferative activity towards
fibrosarcoma, a rare malignant tumor of the fibrous connective
tissue around the bones. MR Guimarães et al. reported that
curcumin was able to inhibit cytokine gene expression in
diseased periodontal tissue. They discovered curcumin-induced
inactivation of IL-6, and IL-11 in a dose-dependent manner. |
|
|
How may
Curcumin work against Rheumatoid arthritis and Osteoarthritis? |
|
The
potential of curcumin against arthritis was first reported in
1980 in a short-term, double-blind, crossover study involving 18
young patients with rheumatoid arthritis. In this study,
curcumin’s efficacy was compared with that of the prescription
drug phenylbutazone. Patients were randomly assigned to receive
either curcumin (1.2 g/day) or phenylbutazone (0.3 g/day) for 2
weeks. Curcumin was well-tolerated, had no adverse effects, and
exerted an anti-rheumatic activity identical to that of
phenylbutazone as shown by improvement in joint swelling,
morning stiffness, and walking time. Curcumin can reduce joint
inflammation and alleviate pain symptoms, mainly due to its
anti-inflammatory and cartilaginous protective effects. In
primary cultured chondrocytes, curcumin inhibited the mRNA
expression of pro-inflammatory mediators IL-1β and TNF-α, MMPs
1.3 and 13, and ADAMTS5, and upregulated the chondroprotective
transcriptional regulator Cbp/p300 interacting transactivator
with ED-rich tail 2. Curcumin reduces the synthesis of
inflammatory mediators, such as TNF-α, IL-17, IL-1β,
transforming growth factor-β (TGF-β), and cyclooxygenase-2 and
reduces the cartilage and synovial inflammation of rat models of
arthritis induced by lipopolysaccharide, Collagen II and
Monoiodoacetic acid. Curcumin exerts an anti-inflammatory effect
by inhibiting TLR4 pathway and its downstream NF-κB signaling
pathway. Activation of NF-κB pathway not only down-regulates
pro-inflammatory factors, but also inhibits the expression of
matrix degrading enzymes. Curcumin inhibited IL-1β-induced MMP-1
and MMP-3 production by inhibiting AP-1 and NF-κB signaling
Pathway activation. Arthritis is an inflammatory autoimmune
disease characterized by chronic inflammation of the synovial
joint that can lead to severe joint injury. IL-10 plays an
important role in the development of rheumatoid arthritis.
Curcumin has anti-inflammatory effect and can regulate TLR-4
receptor and its downstream pathway.65 Curcumin can
down-regulate the levels of TNF-α, IL-1β, IL-6, IL-12, IL-15,
and IL-8 in macrophages, and up-regulate the level of IL-10.
Curcumin effectively alleviates MSU-induced inflammatory
response by inhibiting TLR4/NF-κB signaling pathway and NLRP3
inflammasome activity. Curcumin is a natural anti-inflammatory
drug. Numerous preclinical studies have demonstrated its
beneficial effect on arthritis. Clinical trials focused on the
treatment of knee osteoarthritis. In a clinical trial of
turmeric extract in the treatment of knee osteoarthritis,
turmeric extract inhibited inflammation and improved clinical
symptoms, as well as reduced IL-1β and oxidative stress.
Turmeric extract was more effective than placebo for knee pain.
Motahar Heidari-Beni et al produced an herbal formulation
consisting of turmeric extract, black pepper and ginger. In
patients with knee osteoarthritis, this compound raises
prostaglandin E2 (PGE2) levels similar to naproxen. In a
randomized, pilot study, 45 patients diagnosed with arthritis
were randomized into three groups with patients receiving
curcumin (500 mg) and diclofenac sodium (50 mg) alone or their
combination. Results show that curcumin administration showed
the significantly improvement in overall Disease Activity Score
and American College of Rheumatology compare with diclofenac
sodium. Clinical trials of curcumin in the treatment of
arthritis have produced promising results. Currently
curcumin-containing dietary supplements are widely used for
joint health. In another recent study,
curcumin alone (0.5 g) and in combination with diclofenac sodium
(0.05 g) was found to be safe and effective in 45 patients with
rheumatoid arthritis. Furthermore, the level of CRP was
suppressed in these patients after curcumin administration. Several studies have shown the anti-arthritic effects of
curcumin in humans with osteoarthritis and rheumatoid arthritis
(RA). In a randomized double-blind placebo-controlled trial, 40
subjects with mild-to-moderate degree knee osteoarthritis were
randomly assigned to receive either curcuminoid (500 mg/day in
three divided doses; n = 19) with 5 mg piperine added to each
500-mg dose or a matched placebo (n = 21) for six weeks. There
were significantly greater reductions in the visual analog scale
(VAS) (p < 0.001), Western Ontario and McMaster Universities
Osteoarthritis Index (WOMAC) scores (p = 0.001), and Lequesne’s
pain functional index (LPFI) (p = 0.013) scores in the treatment
group compared with the placebo group. This suggests that
curcumin may offer an alternative to NSAIDS for patients with
osteoarthritis seeking treatment but experiencing negative side
effects. This was supported by results from a pilot study
showing that a dose of 2 grams of curcumin had an analgesic
effect in subjects with acute pain but without a diagnosis of
osteoarthritis . At this dose, the activity was higher than that
associated with 500 mg of acetaminophen, while a lower dose (1.5
g, 300 mg of curcumin) gave only transient and often inadequate
relief of pain, indicative of suboptimal therapeutic plasma
concentrations. This supports the use of 2 g (higher than
needed for inflammation) curcumin for relief of pain as a
potential alternative to NSAIDS. Regardless of the mechanism by
which curcumin elicits its effects, it does appear to be
beneficial to several aspects of osteoarthritis , as suggested
by a recent systematic review and meta-analysis that concluded:
“This systematic review and meta-analysis provided scientific
evidence that 8–12 weeks of standardized turmeric extracts
(typically 1000 mg/day of curcumin) treatment can reduce
arthritis symptoms (mainly pain and inflammation-related
symptoms) and result in similar improvements in the symptoms as
ibuprofen and diclofenac sodium. Therefore, turmeric extracts
and curcumin can be recommended for alleviating the symptoms of
arthritis, especially osteoarthritis”. A recent study out of Japan evaluated its relationship with the
inflammatory cytokine known to be involved in in the
rheumatoid arthritis
process. Scientists discovered that curcumin “significantly reduced” these
inflammatory markers. In fact its anti-inflammatory qualities are so strong
a 2007 study compared
curcumin and cortisone and found they were equal in potency. A few
studies have found that curcumin can reduce pain from rheumatoid arthritis
or osteoarthritis, sometimes as much as anti-inflammatory drugs. An
Iranian clinical trial in
Phytotherapy Research in 2014 found
that curcumin taken for six weeks, improved symptoms of knee osteoarthritis,
compared to a placebo. Most
pharmaceutical anti-inflammatories are contraindicated to use over the
long-term, but turmeric is not only safe but beneficial for your overall
wellbeing. Curcumin's anti-inflammatory properties also make it a strong candidate
for treating inflammatory diseases such as osteoarthritis.
A 2014 study in the
Clinical Interventions in Aging found that curcumin extracts "were as
effective as ibuprofen for the treatment of knee osteoarthritis." All current drugs approved for arthritis have anti-inflammatory
activity. Anti-TNF (tumor necrosis factor) therapy has been approved for this
disease. Curcumin has been shown to both suppress the TNF production, block
the action of TNF, and have
activity against arthritis.
When inflammation is reduced, the added benefit is
pain relief. A double-blind, crossover study showed that Curcumin may be effective
in relieving pain and improvements in morning stiffness, walking time, and joint
swelling. A preliminary intervention trial that compared curcumin with a
nonsteroidal anti-inflammatory drug (NSAID) in 18 patients with rheumatoid
arthritis (RA) found that improvements in morning stiffness, walking time,
and joint swelling after two weeks of curcumin supplementation (1.2 g/day)
were comparable to those experienced after two weeks of phenylbutazone
(NSAID) therapy (300 mg/day). In a more recent randomized, open-label study
in 45 RA patients, supplementation with a mixture of all three major
curcuminoids (0.5 g/day for eight weeks) was found to be as effective as
diclofenac (NSAID; 50 mg/day) in reducing measures of disease activity,
tenderness, and swelling joints.
Several
studies
have shown
curcumin’s ability to reduce pain, stiffness, and swelling
in joints afflicted by arthritis. The
Arthritis Foundation suggests that those with arthritis who
wish to seek relief take capsules of curcumin powder, between
400 mg to 600 mg, three times a day. Given that curcumin is a
potent anti-inflammatory compound, it makes sense that it may
help with arthritis. Several studies show this to be true. In a
study in people with rheumatoid arthritis, curcumin was even
more effective than an anti-inflammatory drug (42). Many other
studies have looked at the effects of curcumin on arthritis and
noted improvements in various symptoms. An in vitro
and ex vivo study
found that curcumin has anti-platelet and prostacyclin
modulating effects compared to aspirin, indicating it may have
value in patients prone to vascular thrombosis and requiring
anti-arthritis therapy. In a randomized, pilot study, curcumin
administration (500 mg, b.i.d., p.o., for 8 weeks) reduced
Disease Activity Score in rheumatoid arthritis without any
adverse events. In addition, the effect of curcumin was better
than the patients receiving diclofenac sodium (Chandran and Goel
2012). In animal model, curcumin administration (100 mg/kg
orally for two weeks) showed anti-arthritic activity by
augmenting the generation of somatostatin in the small intestine
of Freund’s complete adjuvant induced arthritic rats (Yang et
al. 2015). Curcumin (50 mg/kg, i.p.) attenuated the severity and
progression of collagen induced arthritis in DBA/1 J mice by
decreasing the production of B cell-activating factor belonging
to the TNF family in spleen cells and serum as well as reduction
of serum IL-6 and IFNc(Huang et al. 2013). It reduced the pannus
formation process that produced through articular cartilage of
collagen induced arthritic rats (Kamarudin et al. 2012). In in
vitro studies, curcumin treatment (2.5–10 mmol for 14 days)
inhibited the osteoclastogenic potential of peripheral blood
mononuclear cells obtained from patients with rheumatoid
arthritis by decreasing stimulation of ERK 1/2, c-Jun N-terminal
kinase, p38 and downregulating nuclear factor of activated T
cells (NFATc1), receptor activator of NF-jB and c-Fos
expression, and reduce bone deterioration during rheumatoid
arthritis (Shang et al. 2016b). Curcumin treatment efficiently
blocked phorbol 12-myristate 13 acetate and IL-1b-induced
upregulation of IL-6 expression in MH7A cells and
Fibroblast-like synoviocytes. In addition, it inhibited NF-jB
activation, induced ERK1/2 dephosphorylation, exerted strong
anti-inflammatory activity and induced apoptosis in
fibroblast-like synoviocytes, which might use as a natural
remedy for the management of rheumatoid arthritis (Kloesch et
al. 2013). Mechanistically, curcumin blocks certain cytokines
and enzymes that lead to inflammation, and this sheds light on
the possibility of curcumin for the treatment of rheumatoid
arthritis. Osteoarthritis is the most common type of arthritis,
which is characterized by pain, tenderness, bone spurs,
stiffness, and loss of function in the joints (Farzaei et al.
2015). In a randomized, double-blind, placebo-controlled
prospective study, chronic administration of curcumin (180
mg/day, p.o., for 8 weeks) significantly reduced knee pain in
osteoarthritic patients as compared to the placebo group
(Nakagawa et al. 2014). Curcumin treatment showed protection
against osteoarthritis by inhibiting the release of inflammasome
NLRP3, followed by downregulation of IL-1b, TNF-a and cleaved
caspase-1 in surgical mouse osteoarthritis model (Sun et al.
2017). Mechanistically, curcumin reduced MMP-2, MCP-1,
L-selectin, advanced oxidation protein product levels,
suppressed the release of proteoglycans, expression of
cyclooxygenase, prostaglandin E2 and inflammatory cytokines
while increased CD47 levels in chondrocytes (Liu et al. 2016;
Chin 2016). |
|
How may Curcumin work against
Gastrointestinal and Inflammatory bowel disease such as Crohn's disease, Ulcerative Colitis, Irritable bowel syndrome,
gastritis, dyspepsia, gastric and peptic ulcers? |
Six hundred milligrams of curcumin
five times a day for 12 weeks to individuals with peptic ulcers
could prevent ulcer development. Abdominal pain along with other
symptoms has greatly decreased with curcumin within 1–2 weeks.
Kim et al. (2005) found that orally administered ethanolic
C. longa extract decreased stomach acid, gastric juice
secretion, and ulcer initiation in male rats by inhibiting H2
histamine receptors, which is similar to the effects of
ranitidine. Similarly, the antiulcer action of C. longa
ethanolic extract was seen as it lowers ulcer index in addition
to stomach acidity significantly. C. longa extract also
suppressed hypothermic-restraint stress depletion of stomach
wall mucus and diminished the severity of necrotizing
agent-induced lesions. Curcumin significantly protects against severe colitis by inhibiting activation of NLRP3
inflammasomes and production of IL-1β, resulting in improved
weight loss, reduced disease activity index and increased colon
length. Curcumin can inhibit the production of
pro-inflammatory factors which is beneficial to improve
intestinal inflammation in patients with IBD. Curcumin can
effectively induce and maintain symptom relief in patients with
ulcerative colitis, reduce inflammatory markers and improve the
quality of life of patients. Curcumin is derived from natural
products, with high safety, has the capacity for
anti-inflammatory, antioxidant, and regulating autophagy and gut
microbiota. Curcumin is a safe and effective adjuvant agent in
the treatment of IBD. In patients with IBD, curcumin has a
beneficial effect on clinical symptoms, endoscopic relief,
reduction of oxidative stress or inflammatory markers.
Alternatively, curcumin can also play a beneficial role in a
more common intestinal disease. Irritable bowel syndrome is a
functional bowel disorder that classically presents with
symptoms of abdominal pain, bloating, and altered bowel habits
of diarrhea or constipation. The Irritable Bowel Syndrome-
symptom severity score (IBS-SSS) was used to evaluate the effect
of curcumin on patients with IBS. Curcumin can effectively
improve IBS-SSS, abdominal pain and other symptoms, and improve
the quality of life of patients. Research suggest that the
beneficial effects of curcumin on IBS may be due to its
anti-inflammatory effect. Because of its scientifically
evidenced characteristics to interfere with a variety of signal
transduction pathways, transcription factors, and cellular
processes, curcumin can potentially be applied in the treatment
of many diseases (inflammatory disorders in particular). In this
context, curcumin has been used to treat gastrointestinal
diseases such as indigestion, flatulence diarrhea, and even
gastric and duodenal ulcers. Kwiecien and colleagues summarize
in their review curcumin’s protective effects against esophageal
and gastric disorders. In addition, curcumin is potentially
efficacious against intestinal inflammatory diseases. Burge and
colleagues discuss the beneficial effects of curcumin on the
microbiome, its antimicrobial properties, changes in cytokine
profiles, and alterations to immune cell maturation and
differentiation. The combination of all these molecular actions
makes curcumin a promising candidate to treat intestinal
inflammatory diseases like necrotizing enterocolitis, Crohn’s
disease, and ulcerative colitis. Crohn’s disease is a pro-inflammatory disease. All current drugs approved
for this disease have anti-inflammatory activity. Anti-TNF therapy has been
approved for this disease. Curcumin has been shown to both suppress the TNF
production and the TNF action. Several clinical trials suggest that curcumin can
help people with this inflammatory bowel disease.
Clinical Gastroenterology and Hepatology featured a study in 2015
which found that in people with mild to moderate ulcerative colitis who took
standard medication (mesalamine), the addition of a high-dose curcumin
supplement helped half of them achieve remission after four weeks; none of
those given a placebo benefited. Curcumin taken orally has been shown to have
activity against inflammatory bowel disease. Study results
suggest that Curcumin could have a protective role in ulcerative colitis via
regulation of oxidant/anti-oxidant balance and modulation of the release of some
inflammatory endocoids, namely TNF-alpha and NO.
Curcumin maintenance
therapy for ulcerative colitis: randomized, multicenter, double-blind,
placebo-controlled trial. The development of DSS-induced
colitis was significantly attenuated by curcumin. Inhibition of p38 MAPK
signaling by curcumin could explain the reduced COX-2 and iNOS immunosignals and
the nitrite production in colonic mucosa, reducing the development of chronic
experimental colitis. In addition, Curcumin seems promising with regards to remission in patients with quiescent Ulcerative
Colitis. Preliminary evidence suggests that curcumin might be useful as an
add-on therapy to control disease activity. One multicenter, randomized,
double-blind, placebo-controlled study has examined the efficacy of curcumin
enema (2 g/day) in the prevention of relapse in 82 patients with quiescent
UC . Six-month treatment with curcumin significantly reduced measures of
disease activity and severity and resulted in a lower relapse rate than with
placebo in subjects on standard-of-care medication (sulfasalazine or
mesalamine). In another randomized controlled trial in active UC patients
treated with mesalamine, the percentage of patients in clinical remission
was significantly higher after a one-month treatment with oral curcumin (3
g/day) than with placebo.
Curcumin in
Combination With Mesalamine Induces Remission in Patients With
Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial.
Another
study conducted in the UK revealed that those with IBS who
took two capsules of turmeric every day over the course of eight
weeks experienced less abdominal pain and had more consistent
bowel movements. A recent study from the
American Gastroenterological Association suggests that
curcumin may help ease ulcerative colitis, a form of
inflammatory bowel disease that
causes ulcers in the digestive tract. Turmeric has been known
for a long time to help with digestive problems. For example, it
helps very well with bad digestion of fats. But even if you
suffer from irritable bowel syndrome or Crohn’s disease,
turmeric can mean a great deal to you. This is partly because it
prevents inflammation in the intestinal wall. Curcumin can also
be a solution for people with a stomach ulcer. Curcumin has a
significant role in cases of gastric ulcers. An open, phase II
trial was performed on 25 patients with endoscopically diagnosed
gastric ulcer. Participants were provided 600 mg powdered
turmeric, five times daily. After 4 weeks, ulcers had completely
healed in 48% patients. The success rate increased over time,
with 76% being ulcer free after 12 weeks of treatment. No
significant adverse reactions or blood abnormalities were noted.
In a clinical study, five patients with a stomach ulcer were
given five times 600 mg of curcumin every day for 12 weeks.
Almost half of them had no stomach ulcers after four weeks, and
by the end of the study, the gastric ulcer had disappeared by
76%. In a multi-centered, double-blind, placebo-controlled
trial, curcumin treatment (1 g after breakfast and 1 g after the
evening meal with mesalamine or sulfasalazine for 6 months)
appeared to be a safe and promising drug candidate for
maintaining remission in ulcerative colitis patients (Hanai et
al. 2006). Holt et al. (2005) carried out a pilot study to see
how curcumin therapy affected IBD patients who had earlier
received standard UC or CD therapy. Curcumin with standard
treatment exerts more beneficial effects than placebo plus
conventional UC treatment in maintaining recovery, according to
Hanai et al. (2006). Bundy et al. (2004) examined that abdominal
pain or discomfort score was lowered significantly by 22% and
25% in the one- and two-tablet group volunteers, respectively,
and revealed the role of C. longa on IBS pathology. In animal study, curcumin administration reversed
inflammation of the colonic mucosa, restored colonic length, and
reduced colonic weight and colonic damage. In addition, curcumin
increased the number of T regulator (Treg) cells while
suppressed the secretion of IL (2, 6, 12 and 17) and TNF-a.
Curcumin is known to downregulate the expression of
co-stimulatory molecules CD254 [RANKL], CD54 [ICAM-1], CD205,
CD256 [RANK], TLR4 and CD252[OX40 L] against 2, 4,
6-trinitrobenzene sulfonic acid induced colitis in mice (Zhao et
al. 2016b). In a recent experimental study, curcumin
administration demonstrated therapeutic potential through
downregulation of colonic TNF-a, myeloperoxidase (MPO), p-38MAPK
and p-p38MAPK expressions in mouse murine ulcerative colitis
model (Khoury et al. 2015). Curcumin treatment is known to
reduce interferon (IFN)-c, COX-1, COX-2, TNF-a, NF-jB and iNOS
expression. Further, it was reported that curcumin treatment
reduces inflammation of colon due to inhibition of chemokinesis
and neutrophil chemotaxis (Wan et al. 2014). Moreover, curcumin
mitigated inflammatory bowel disease via influencing MAPK, ERK
pathways, increasing antioxidants, inducing free radical
scavenging and MPO inhibition (Baliga et al. 2012).
Mechanistically, curcumin treatment reduced ulcerative colitis
by inhibiting neutrophil chemotaxis, suppressing the secretion
of inflammatory cytokines and inducing antioxidant effects. In a
pilot study, administration of curcumin (350 mg, t.i.d. for 1
month followed by 350 mg q.i.d. for another 2 month) reduced the
inflammatory response in Crohn’s disease condition. In addition,
it reduced the erythrocyte sedimentation rates and Crohn’s
Disease Activity Index in patients (Holt, Katz, and Kirshoff
2005). Oral administration of curcumin (40 mg/kg, for 21 days)
reversed the visceral nociceptive response to graded intensity
of colorectal distension and pellet output associated with
chronic acute combined stress mediated depressive and anxiety
like behaviors in rats. Mechanistically, curcumin treatment
increased the levels of serotonin, BDNF and pCREB in the
hippocampus, while these levels were reduced in the colonic of
chronic acute combined stressed rats (Yu et al. 2015). The
5-HT1A receptor is known to be involved in the mode of action of
curcumin for the management of visceral hypersensitivity in rats
with irritable bowel syndrome. In addition, curcumin
administration causes remarkable decrease in visceromotor
response to colorectal distension in rats (Farzaei et al.
2016b). Adjunctive therapy of curcumin (500 mg/day for 4 weeks)
with anti-helicobacter regimen ameliorated the symptoms of
dyspepsia in peptic ulcer patients (Khonche et al. 2016). In
animal study, curcumin administration reduced the restraint
stress and water immersion stress-induced gastric lesions by
increasing gastric blood flow and attenuating pentagastrin or
histamine-stimulated secretion of gastric acid. In addition, the
expression levels of iNOS, COX-2 and TNF-awas significantly
downregulated in gastric mucosa of curcumin administered rats
exposed to restraint stress and water immersion stress,
resulting in gastroprotective effect (Czekaj et al. 2016).
Curcumin (10, 50 or 100 mg/kg orally for three days) dose
dependently reduced LPO and gastric ulcer area and restored GPx,
CAT and SOD levels in gastric mucosa of naproxen treated rats
(Kim et al. 2016b). Curcumin treatment reversed stress mediated
gastric ulceration in rats by reducing the hemorrhage of gastric
mucosa, increasing gastric pH values and attenuating ulcer index
which is associated with downregulation of histone H3
acetylation at H þ , K þ -ATPase promoter gene (He et al.
2015a). Curcumin treatment decreased pepsin activity, total acid
output and ulcer index alongside reduced MDA level, ameliorated
mucin, CAT, NO and SOD in gastric mucosa of indomethacin-induced
ulcer in rats (Morsy and El-Moselhy 2013). Additionally,
curcumin ameliorated indomethacin-induced gastric ulcer by
inducing angiogenesis and collagenization of gastric tissue via
upregulation of TGF-b, MMP-2, membrane type 1-MMP and VEGF
expressions in ulcerated tissues (Sharma et al. 2012). The
biological mechanism of curcumin to combat peptic ulcer is
mainly due to its antioxidant and anti-inflammatory activities.
The gastroprotective effect is also due to inhibition of acid
release, amelioration of blood flow, angiogenesis and
collagenization of gastric tissue (Sharma et al. 2012; Yadav et
al. 2013). Clinically, curcumin administration (40 mg orally,
three times a day, for four weeks) reduced the production of
IL-1b, IL-8, COX-2 and TNF-ain gastric mucosa, and attenuated
inflammation in gastritis patients infected with H. pylori
bacteria (Koosirirat et al. 2010). In a randomized clinical
trial, administration of curcumin (700 mg orally, three times a
day, for 4 weeks) reduced the level of MDA, DNA oxidative
damage, endoscopic and chronic inflammation scores and glutathione peroxides in gastritis patients (Judaki et al.
2017). In animal model, curcumin treatment downregulated the
expression of chemokines such as CXCL1, CCL5, CXCL10, CXCL11,
CCL20 and Chemokine (C-C motif) ligand 25 in stomach of mice
bearing Helicobacter pylori induced gastric inflammation. In
addition, curcumin decreased secretion of IL-1b, IL-6 and
TNF-aduring H. pylori infection. Further, curcumin
supplementation reduced the macromolecular leakage, MyD88
expression and NF-jB activation in gastric cells (Santos et al.
2015). Study suggested that antimicrobial activity of curcumin
against H. pylori is responsible for the management of gastritis
in mice (De et al. 2009). The biological effect of dietary
polyphenol curcumin to reduce chronic gastritis is mainly due to
its antioxidant, anti-inflammatory and anti-bacterial activities
(Yadav et al. 2013), therefore, it can be recommended as a novel
drug for management of gastritis. One open-label study evaluated
the efficacy of curcumin in five patients with ulcerative
proctitis and in five patients with Crohn disease.
Significant decrease in symptoms as well as in inflammatory
indices (erythrocyte sedimentation rate and CRP) were observed
in all patients with proctitis This study suggests the efficacy
of curcumin against IBD. Another study evaluated the efficacy of
curcumin as maintenance therapy in 89 patients with quiescent
ulcerative colitis. The relapse rates were 4.65% in the
curcumin-treated group and 20.51% in the placebo group. In
another recent study, ingestion of oral curcumin at 500 mg/day
along with prednisone was associated with clinical and
endoscopic remission in a 60-year-old woman with a 17-year
history of left-sided ulcerative colitis and enteropathic
arthropathy (34). The patient had been examined for persistently
active colitis in December 2009. Both a clinical and endoscopic
evaluation confirmed the diagnosis. Previously, multiple
mesalamine preparations, sulfasalazine, and steroid enemas had
not been effective, and the patient had required multiple
courses of steroids for disease exacerbation. She refused
azathioprine/6-mercaptopurine and anti-TNF treatment because of
possible adverse effects. In addition to 40 mg of prednisone,
500 mg of curcumin per day was given to the patient. After
receiving curcumin and prednisone treatment for 1 year, the
patient’s bowel movements had gone to two per day without blood,
she was no longer taking steroids, and she was feeling well. She
remained in clinical remission at further clinical evaluations
in April, July, and December 2010. A colonoscopy performed in
September 2010 showed no ulceration and biopsies consistent with
chronic inactive ulcerative colitis (34). Thus, based on this
case study, curcumin represents a viable treatment alternative
or adjunctive therapy in the management of chronic ulcerative
colitis. A recent study assessed the effect of curcumin on the
levels of p38 mitogen-activated protein kinase (p38 MAPK),
IL-1β, IL-10, and matrix metalloproteinase-3 (MMP-3) in the gut
of children and adults with IBD. Results indicated suppression
in p38 MAPK activation, reduction in IL-1β, and enhancement in
IL-10 levels in curcumin-treated mucosal biopsies. Furthermore,
dose-dependent suppression of MMP-3 in colonic myofibroblasts
was observed after curcumin treatment. Another study conducted
with eight healthy participants reported that turmeric has the
potential to increase bowel motility and to activate
hydrogen-producing bacterial flora in the colon. |
|
How may Curcumin work against
metabolic diseases such as polycystic ovary syndrome, metabolic
syndrome, and obesity? |
Effect of Curcumin on Metabolic Syndrome | The role of curcumin in reducing oxidative stress and
inflammation has far-reaching implications when it comes to
overall metabolic health. The idea that curcumin can attenuate
systemic inflammation has implications for metabolic syndrome
(MetS), which includes insulin resistance, hyperglycemia,
hypertension, low high-density lipoprotein cholesterol (HDL-C),
elevated low-density lipoprotein cholesterol (LDL-C), elevated
triglyceride levels, and obesity, especially visceral obesity.
Curcumin has been shown to attenuate several aspects of
metabolic syndrome by improving insulin sensitivity, suppressing
adipogenesis, and reducing elevated blood pressure,
inflammation, and oxidative stress. In addition, there is
evidence that curcuminoids modulate the expression of genes and
the activity of enzymes involved in lipoprotein metabolism that
lead to a reduction in plasma triglycerides and cholesterol and
elevate HDL-C concentrations. Curcumin has been shown to have a
role in decreasing angiogenesis and adipogenesis by suppressing
CCAAT/enhancer-binding protein alpha and PPAR expression and by
lowering cholesterol levels. Moreover, curcumin has the ability
to upregulate the gene expression of pancreatic glucose
transporter 2 (GLUT2), GLUT3, and GLUT4, thus stimulating
insulin secretion. In a randomized double-blind
placebo-controlled trial with a parallel-group design, 117
subjects with metabolic syndrome received either 1 g curcumin
plus 10 mg piperine to increase absorption or a placebo.
Analysis revealed significant reductions in serum concentrations
of TNF-α, IL-6, transforming growth factor beta (TGF-b), and
monocyte chemoattractant protein-1 ( MCP-1) following curcumin
piperine supplementation. The results of this study suggest that
curcumin piperine supplementation significantly decreases serum
concentrations of pro-inflammatory cytokines in subjects with
metabolic syndrome. In addition, the study looked at the
cholesterol-lowering properties and found that curcuminoids were
more effective than the placebo in reducing serum LDL-C,
non-HDL-C, total cholesterol, triglycerides, and lipoprotein a
(Lp(a)), in addition to elevating HDL-C concentrations. The
effects of curcuminoids on triglycerides, non-HDL-C, total
cholesterol, and Lp(a) remained significant after adjustment for
baseline values of lipids and body mass index. From the same
study, the authors also reported markers of oxidative stress.
There was a significant improvement in serum SOD activities (p <
0.001) and reduced MDA (p < 0.001) and C-reactive protein (CRP)
(p < 0.001) concentrations in the group receiving the curcumin
with piperine compared to the placebo group. Quantitative data
synthesis revealed a significant effect of curcuminoids vs.
placebo in reducing circulating CRP concentrations. The authors
concluded that short-term supplementation with a
curcuminoid-piperine combination significantly improves
oxidative and inflammatory status in patients with metabolic
syndrome. Curcuminoids with piperine could therefore be regarded
as natural, safe, and effective CRP-lowering agents.
Inflammatory cytokines were also measured in the above study.
Mean serum IL-1β (p = 0.042), IL-4 (p = 0.008), and vascular
endothelial growth factor (VEGF) (p = 0.01) were found to be
significantly reduced by curcumin piperine therapy. The authors
suggest that the findings indicate that curcumin piperine may
exert immunomodulatory effects via altering the circulating
concentrations of IL-1β, IL-4, and VEGF. In a randomized
double-blind placebo-controlled crossover trial, 36 obese adults
received either 1 g curcumin and 10 mg piperine or a placebo for
30 days followed by a two-week washout period, after which they
received the other treatment. A significant reduction in serum
triglyceride concentrations was observed. Effect of
Curcumin on Obesity |
Obesity is Inflammatory Disease.
Studies have suggested that properties in curcumin may have a positive effect on blood sugar
and blood pressure and may also promote weight loss and prevent
obesity. Scientists led by Dr David
Fairlie from the University of Queensland, Australia, have found
abnormal amounts of an inflammatory protein called PAR2 in the
fat tissues of overweight and obese rats and humans. PAR2 is
also increased on the surfaces of human immune cells by common
fatty acids in the diet. When obese rats on a diet high in sugar
and fat were given a new oral drug that binds to PAR2, the
inflammation-causing properties of this protein were blocked, as
were other effects of the high-fat and high-sugar diet,
including obesity itself. In the prevention and treatment of obesity and metabolic
syndrome, Curcumin has been reported to modulate numerous targets that have been
linked to obesity and insulin resistance. 1) Curcumin has been shown to downregulate the expression of TNF in various tissues.
2) Curcumin can suppress NF-κB activation induced
by a wide variety of inflammatory agents through inhibition of degradation of
IκBα. 3) Curcumin can inhibit the activation of IKK linked to the activation
of NF-κB, and this leads to the suppression of expression of inflammatory
biomarkers such as cyclooxygenase-2 (COX-2) and vascular endothelial growth
factor. 4) Curcumin has been shown to downregulate the expression of
various NF-κB-regulated proinflammatory adipocytokines including chemokines
(such as MCP-1, MCP-4, and eotaxin)
and interleukins (IL-1, IL-6, and IL-8). Curcumin also suppressed the expression
of plasminogen activator inhibitor type-1 through the inhibition of the
transcription factor early growth response (Egr)-1 gene product that has been
closely linked with insulin resistance and obesity. 5) Curcumin has been reported
to mimic most antidiabetic drugs in that it activates PPAR-γ in hepatic stellate
cells. 6) Curcumin has been shown to downregulate activation of
c-Jun NH2 terminal kinase. 7) Curcumin has been shown to inhibit the Wnt/β-catenin
pathway, which is closely linked to obesity. Later studies have indicated that
Curcumin inhibits Wnt pathway signaling through downregulation of the
transcription coactivator p300. Another potential mechanism by which Curcumin
could inhibit β-catenin signaling is through inhibition of glycogen synthase
kinase (GSK)-3β, which directly causes the phosphorylation of β-catenin.
Curcumin was found to inhibit GSK-3β with as little as 66 nM IC50 (32).
8) Curcumin has been shown to induce the expression of hemeoxygenase (HO)-1
through the activation of Nrf2 in pancreatic cells and thus mediate the survival
of these cells. 9) Curcumin downregulates the secretion of insulin-like growth
factor-1 but induces the expression of insulin-like growth factor binding
protein-3. 10) Curcumin interrupts leptin signaling
by reducing phosphorylation levels of the leptin receptor (Ob-R) and its
downstream targets. 11) Curcumin suppresses gene expression of Ob-R in
HSCs. 12) Curcumin has been reported to increase the expression of
adiponectin, which negatively controls obesity. A study conducted by researchers
at
Tufts University found that curcumin, the predominant
polyphenol in turmeric, suppressed the growth of fat tissue in
mice and cell models and ultimately reduce weight gain. Two
groups of mice were fed high-fat diets—one supplemented with 500
mg of curcumin per kilogram of weight. The curcumin group did
not gain weight as the high-fat-only group. Clinically,
chronic administration of curcuminoids (comprising curcumin,
bisdemethoxycurcumin and demethoxycurcumin) significantly
decreased serum pro-oxidant-antioxidant balance, oxidative
stress burden (Sahebkar et al. 2013), serum triglycerides
(Mohammadi et al. 2013), VEGF, IL-1band IL-4 in obese patients
(Ganjali et al. 2014). In animal study, curcumin treatment
reduced the level of triglyceride and LDL-cholesterol along-
side increased HDL-cholesterol, which is known to ameliorate
lipoprotein metabolism. Curcumin administration (0.05% w/w of
diet) markedly decreased the plasma level of free fatty acid and
triglyceride in the hamsters fed with high-fat diet (10% coconut
oil and 0.2% cholesterol w/w) (Ganjali et al. 2017). Curcumin
administration (200 mg/kg, dissolved in 0.1% carboxy methyl
cellulose, for 10 weeks) significantly decreased body weight,
adipose weight, liver weight, plasma levels of triacylglycerol,
lipid ratios, hepatic fat accumulation while increased HDL in
fructose-fed rats (Maithilikarpagaselvi et al. 2016). Curcumin
administration alone (80 mg/kg/day, p.o., for 12 weeks)
significantly down-regulated the hepatic expression of sterol
regulatory element-binding proteins-1, sterol regulatory
element-binding proteins-2, 3-hydroxy-3-methylglutaryl-coenzyme
A reductase, mevalonate kinase, 24-dehydrocholesterol reductase,
7-dehydrocholesterol reductase, lanosterol synthase, sterol-
C4-methyl oxidase-like (Sc4mol), squalene synthase, proprotein
convertase subtilisin/kexin type 9, LDL-receptor, acetyl-
coenzyme A carboxylase-1, ATP citrate lyase, acyl-CoA syn-
thetase, fatty acid synthase, fatty acid desaturase-1, fatty
acid desaturase-2, stearoyl-coenzyme A desaturase-1, glycerol-3-
phosphate acyltransferase, glucose-6-phosphatase and phos-
phoenolpyruvate carboxykinase-1 in high fat diet-induced obese
mice. In addition, curcumin administration upregulated the
hepatic phosphorylation of IRS-1, IRS-2 and Akt at serine 473
resulting in reversal of obesity in mice (Ding et al. 2016).
Curcumin administration (200 mg/kg body weight) with high fat
diet for 10 weeks significantly decreased the hepatic ERK and
p38 signaling pathway activation as well as reduced body weight
in rats (Maithili Karpaga Selvi et al. 2015). Curcumin (1 g/kg)
along with high fat diet containing 60% of total calories from
fat (5.1 kcal/g diet) administration for 16 weeks significantly
decreased hepatic lipids levels, lipid peroxidation. Curcumin
(100 or 400 mg/kg) along with high fat diet for 8 weeks
effectively reduced serum fetuin-A levels and hepatic
triglycerides level in obese rats. Curcumin is known to inhibit
NF-jB activation and macrophage infiltration in adipose
tissue. In addition, curcumin downregulated the expression of
the plasminogen activator inhibitor type-1, TNF-aand MCP-1 while
upregulated the expression of adiponectin in adipocytes
(Bradford 2013). In in vitro assay, curcumin downregulated the
expression of axin, GSK-3b, CK1-a, AP-2 (mature adipocyte
marker) and upregulated the expression of Fz2 (Wnt direct
receptor), Wnt10b, LRP5 (Wnt co-receptor), c-Myc and cyclin D1
in 3T3-L1 cells. In addition, curcumin inhibited the
phosphorylation of MAPK, JNK, p38 and ERK thereby rescue the
differentiation of 3T3-L1 cells into adipocytes (Ahn et al.
2010). Curcumin treatment inhibited mitotic clonal expansion
process and downregulated the expression of PPAR-c, kruppel-like
factor 5 and C/EBParesulting in reduced adipocyte
differentiation (Kim et al. 2011). Mechanistically, curcumin
administration inhibits NF-jB activation and macrophage
infiltration, reduces the expression of plasminogen
activator inhibitor type-1, MCP-1, TNFa, very low density
lipoprotein (VLDL), cytokines and leptin alongside induced HO-1,
fatty acid oxidation, APO-A1 and adiponectin level. In addition,
curcumin treatment reduces the incidence of obesity and its
associated risk factors, mainly due to its antioxidant and
anti-inflammatory activities (Alappat and Awad 2010).
Effect of Curcumin on Polycystic Ovary Syndrome (PCOS)
| The latest systematic review and meta-analysis of
randomized-control trials investigated a significant improvement
in fasting glucose, fasting insulin, the homeostasis model
assessment measuring insulin resistance (HOMA-IR), and the
quantitative insulin sensitivity check index (QUICKI) in women
with PCOS who took curcumin in comparison with a placebo group.
Jamilian et al. found that administration of curcumin for 12
weeks in women with PCOS had beneficial effects on glycemic
control, among other things. The researchers reported that
reduced fasting glucose (p = 0.002) significantly increased
insulin sensitivity (p = 0.02), and positive alterations in
serum lipids (i.e., a decrease in total cholesterol (p = 0.001)
and LDL cholesterol (p = 0.001) and an increase in HDL
cholesterol levels (p = 0.01)) in comparison to patients taking
a placebo; in addition, curcumin supplements decreased the
weight of women suffering from PCOS. Other researchers who have
looked at the effects of curcumin on glycemic status, lipid
profile, and high-sensitivity C-reactive protein (hs-CRP) levels
in overweight/obese women with PCOS found that serum insulin,
QUICKI (p < 0.05), and HOMA-IR (p = 0.067) were significantly
improved in the group treated with curcumin. In contrast, the
differences in lipid parameters and hs-CRP levels were not
statistically significant in the curcumin-treated group.
Curcumin may stimulate insulin-mediated glucose uptake through
the phosphatidylinositol 3-kinsase (PI3K)/Akt pathway, which, in
turn, upregulates glucose transporter 4 (GLUT4) in the adipocyte
and skeletal muscle, leading to an increase in glucose levels.
Additionally, curcumin may also enhance GLUT4 and glucose uptake
in adipocytes. Curcumin has been shown to inhibit liver
gluconeogenesis through modulation of 5’AMP-activated protein
kinase (AMPK), thus reducing blood glucose levels. Moreover, the
lipid-lowering potential of curcumin may be a consequence of
curcumin’s ability to decrease the circulatory levels of lipid
peroxides and total serum cholesterol (TC), or to increase the
levels of high-density lipoprotein (HDL). There are some
potential mechanisms that may be responsible for the beneficial
influence of curcumin on lipid profile; for example, curcumin
may suppress the expression of Niemen-Pick C1-like (NPC1)
protein in the intestine, which mediates the cholesterol
absorption of hepatocytes. Curcumin also ameliorates
dyslipidemia and activates the lipid metabolism pathway, which
elevates lipoprotein lipase activity to decrease triglyceride
levels. The hypothesis about the beneficial impact of curcumin
supplementation on women with PCOS is because curcumin may
support the improvement in complications of PCOS by regulating
gene expression—that is, by increasing the gene expression of
superoxide dismutase (SOD) and glutathione peroxidase enzymes
(GPx)—and cellular signaling. One of the first studies on the
effects of curcumin on postprandial glucose and insulin
response, which was conducted in 2010 by Wickenberg et al.
showed the possible effects of curcumin on postprandial insulin
levels. Curcumin is generally assumed to improve the body’s
antioxidant enzymes by impacting related gene expression in
patients with PCOS. In a randomized and double-blinded clinical
trial involving 67 overweight or obese female patients with
PCOS, the effects of curcumin on gene expression of peroxisome
proliferator-activated receptor γ coactivator-1α (PGC-1α) (p =
0.011) and silent information regulator 1 (SIRT1) were reported.
SIRT1 contributes to the deacetylation of the PGC-1α gene,
thereby increasing the rate of thermogenesis and oxidation of
lipids, and is also an NAD+-dependent histone deacetylase in the
pathway of insulin secretion [15]. These results would seem to
suggest that curcumin may improve hormonal profiles in patients
with PCOS due to its support of ovarian function by reducing
inflammation and oxidative stress. Interestingly, Sohrevardi et
al. reported that the hormonal parameter of total testosterone
levels and the biochemical parameters of triglycerides, HDL, and
total cholesterol were significantly improved in the group
taking curcumin together with metformin after three months in
comparison to the group treated with only metformin. The
anti-inflammatory properties of curcumin may mitigate
hyperandrogenism due to its possible role in glucose and lipid
metabolism. Moreover, curcumin has the ability to lower
circulating tumor necrosis factor alpha (TNF-α) and interleukin
6 (IL-6) concentration. Proinflammatory cytokines such as TNF-α
have been found to be significantly higher in PCOS patients
[25]. Moreover, curcumin may exert anti-diabetic effects by
increasing the gene expression of PPAR-γ, which has a
pleiotropic impact on glucose homeostasis and insulin
sensitivity and controls gene expression in lipid and glucose
metabolism. Heshmati et al. [28] reported not only reduced
glucose and insulin plasma levels, but also significantly
reduced serum dehydroepiandrosterone (DHEA) levels (−26.53
μg/dL; p = 0.035) in patients with PCOS who took curcumin
supplements for 12 weeks in doses of 1500 mg per day in
comparison to the placebo patients. To date, there are few
studies that have assessed the influence of curcumin on the sex
hormones in women with PCOS. Regarding proinflammatory
cytokines, Mohammadi et al. [31] investigated the therapeutic
effects of curcumin on TNF-α, IL-6, and C-reactive protein (CRP)
in rats with PCOS. The difference between the curcumin-treated
group and the non-curcumin-treated rats with PCOS was
significant. The results showed decreased IL-6 and CRP, and
interestingly, they observed decreased expression of tumor
necrosis factor alpha (TNF-α) in the granulosa layer and
follicular fluid of follicles and ovarian cysts in the PCOS
group treated with curcumin. |
|
How may Curcumin work
against liver diseaseS such as Non-alcoholic fatty liver disease
(NAFLD) or metabolic-associated fatty liver disease (MAFLD), cirrhosis,
and hepatitis? |
Effect of
Curcumin on Non-Alcoholic Fatty Liver Disease (NAFLD) or
Metabolic-Associated Fatty Liver Disease (MAFLD) |
Curcumin and related phenolics have been linked with the
inhibition of lipid peroxidation, free radical formation (e.g.,
neutralization of superoxide, peroxyl, and hydroxyl radicals
(ROSs), nitric oxide, and peroxynitrite (RNS)) and DNA damage.
Despite obesity and hyperlipidemia, it is also known that
patients with type 2 diabetes have a high prevalence of NAFLD
(up to 70%). The above diseases share multiple cardiometabolic
risk factors and proinflammatory pathways. Różański et al.
analyzed databases and publications that have described the
effects of using curcumin supplementation on biochemical
parameters in MAFLD. They concluded that curcumin may have
therapeutic potential in MAFLD patients. Jalali et al. included
nine relevant randomized controlled trials (RCTs) in their
meta-analysis in order to study the effects of curcumin
supplements on metabolic markers and anthropometric parameters
in patients with NAFLD. As shown in Table 3, the study reported
a significant decrease not only in alanine transaminase (ALT) (p
= 0.049) and aspartate transaminase (AST) (p = 0.032) activity,
but also in serum total cholesterol (TC), LDL, FBS (p = 0.027),
HOMA-IR (p = 0.031), serum insulin, and waist circumference
(WC). After a meta-regression analysis of the duration and a
dosage-based analysis, a significant change in BMI was
indicated, and a subgroup analysis (age-based and TC-based) also
indicated a significant decrease in TG. The study investigated
changes in two-month and three-month supplementation with
curcumin. The authors concluded that the use of curcumin in the
analyzed studies had a beneficial effect on both metabolic and
anthropometric parameters in patients with NAFLD. Curcumin administration (60
mg/kg for 4 weeks) inhibited the bio- synthesis of unsaturated
fatty acids and fatty acids synthesis in ethanol treated mice.
In addition, ethanol induced hepatic steatosis was reversed by
curcumin treatment (Guo et al. 2017). Animal studies have shown
that curcumin administration reduced the ethanol-induced
increase in MDA content, decreases the levels of aspartate
aminotransferase (AST) and lactate dehydrogenase (LDH), and
increases the GSH levels. In addition, it is known to reduce
fatty liver, oxidative stress, inflammation and necrosis (Nabavi
et al. 2014; Nanji et al. 1999; Ghorbani, Hajizadeh, and
Hekmatdoost 2016). Non-alcoholic fatty liver disease is an
umbrella term for a variety of pathological conditions including
steatosis, fibrosis, cirrhosis and steatohepatitis, caused by
accumulation of fat in the liver. It is closely correlated with
metabolic syndrome, obesity, overweight and type 2 diabetes in
pediatric and adult individuals (Nabavi et al. 2014). In
randomized placebo-controlled trial, curcumin administration (70
mg/day for two months) significantly reduced the liver fat
content, triglycerides, LDL-cholesterol, serum levels of total
cholesterol, body mass index, ALT, AST, glycated hemoglobin and
glucose in patients with nonalcoholic fatty liver disease as
compared to placebo group (Rahmani et al. 2016). Additionally,
curcumin upregulated the expression of adiponectin precursor and
reduced its methylation in experimental model of fatty liver
disease (Park et al. 2016). In methionine and choline feed
deficient mouse model, curcumin administration inhibited the
activation of NF-kB and reduced the inflammatory recruitment in
steatohepatitis (Leclercq et al. 2004). Curcumin administration
downregulated the intrahepatic expression of procollagen type
I, CD11b, tissue inhibitor of metalloprotease (TIMP)-1, monocyte chemoattractant protein-1 and a-smooth muscle-actin in
methionine and choline feed deficient mouse model of
steatohepatitis alongside reduced the oxidative stress in
cultured stellate cells (Vizzutti et al. 2010). Curcumin
administration reduced the serum hepatic markers viz., AST, ALT
and MDA thereby attenuated lipopolysaccharide/d-galactosamine
induced liver damage in rats. In the same study, curcumin
administration reduced the NF-jB activation and TNF-a level in
liver and serum. Furthermore, curcumin upregulated
Nrf-2-dependent antioxidant defense genes like quinone (NQO-1),
NAD(P)H dehydrogenase, glutamate-cysteine ligase and heme
oxygenase-1 which is responsible for the hepatoprotective
activity (Xie et al. 2017). Curcumin administration ameliorated
the barrier integrity of intestine, reduced ectopic fat
deposition in liver and modulated the gut microbiota which in
turn reversed hepatic steatosis in high fat diet fed rats (Feng
et al. 2017). Curcumin administration elicited hepatoprotective
effect via reversal of reduced GPx, CAT and SOD levels in
tartrazine induced liver injury. In addition, it reduced the
intracellular vacuolization, dilation of central vein and
sinusoids as well as necrosis in hepatotoxic rats (El-Desoky et
al. 2017). Recent experimental evidence suggests that curcumin
administration reduced Gr1hi monocytes infiltration in liver,
downregulated the expression of MCP-1, TNF-aand TGF-b1 in mouse
model of CCl 4 induced liver fibrosis (Huang et al. 2016b).
Effect of Curcumin on Cirrhosis | It was reported that curcumin
administration prevents bile duct ligation induced cirrhosis in
rats via inhibition of oxidative stress and downregulation of
TGF-b(Reyes-Gordillo et al. 2008). Curcumin administration ameliorated the functional properties of
hepatocytes and downregulated the expression of NF-jB and iNOS
in liver of biliary duct ligated rats (Barta et al. 2015).
Effect of Curcumin on Hepatotoxic Ailments
| Curcumin is said to increase apoptosis in injured hepatocytes
while also reducing inflammatory effects, hepatic fibrogenesis,
and substantially liver injury. The hepatoprotective attribute
of curcumin might be due to direct free radical scavenging
mechanisms, boosting glutathione levels, and assisting in liver
detoxification. Curcumin has hepatoprotective activity similar
to that of silymarin. From studies, it can be concluded that
curcumin has hepatoprotective potential in various
including carbon tetrachloride (CCl4), acetaminophen (paracetamol)
and galactosamine. This hepatoprotective effect is mainly a
observed due to the antioxidant activity of curcumin along with
its ability to decrease the formation of proinflammatory
cytokines. Administration of curcumin is resulted in decrease of
liver injury. Aflatoxin-induced biliary hyperplasia, lipid
alterations, and necrosis were likewise cured by curcumin.
Sodium curcuminate is a salt of curcumin that has choleretic
effects, boosting biliary excretion of bile salts, cholesterol,
bilirubin, and bile solubility, thus helping to prevent and
treat cholelithiasis. This could be related to the antioxidant
capacity of curcumin’s phenolic groups. Tacrine is well-known
for its hepatotoxic and T-cell-destructive properties. Curcumin
was over ten times more efficient than standard therapy,
ascorbic acid, in research involving human hepatocytes cells
that had been disrupted by tacrine (Song et al., 2001). Effect of Curcumin on Hepatitis | A recent
in vitro study demonstrated that curcumin treatment time and
dose dependently reduce the expressions of hepatitis B virus
surface antigen and e-antigen in hepatitis B virus transfected
HepG2.2.15 cell line. In addition, curcumin inhibited
replication of hepatitis B virus gene via down-regulation of
cccDNA-bound histone acetylation (Wei et al. 2017). Study
revealed that curcumin treatment inhibits hepatitis B virus via
downregulation of the metabolic coactivator peroxisome
proliferator-activated receptor gamma coactivator 1-alpha
(PGC-1a). It has been reported that combination of
nucleotide/nucleoside analog with curcumin can synergistically
reduce the replication of hepatitis B virus (Nabavi et al. 2014;
Mouler Rechtman et al. 2010). It was reported
that co-incubation of hepatitis C virus with curcumin and its derivatives
potently inhibits the entry of all major hepatitis C virus genotypes. Curcumin affects the membrane fluidity
resulting in impairment of viral binding and fusion thereby
inhibits cell-to-cell transmission in human liver cells
(Colpitts et al. 2014). Co-administration of curcumin and
IFN-a profoundly inhibited hepatitis C virus replication in Huh7 cells and
found to be effective against hepatitis C virus infections (Kim et al. 2010).
Moreover, curcumin exhibited anti-HCV activity by inducing HO-1
and modulating ERK and NF-jB activities in Huh7.5 cells
expressing the hepatitis C virus genotype 1 b subgenomic replicon (Chen et al.
2012). Mechanistically, curcumin shows hepatoprotective action
due to its antioxidant effects and inhibitory activity against
NF-jB that is known to regulate different pro-fibrotic and
pro-inflammatory cytokines. Additionally, curcumin supple-
mentation reduced liver marker enzymes, cholesterol levels and
replication of hepatitis B and C viruses (Nabavi et al. 2014). |
|
How may Curcumin work as
an antimicrobial, Antibacterial, Antiviral, antiparasitic, and Antifungal? |
Curcumin has antiviral potential (von
Rhein et al., 2016) even for HIV; inhibiting HIV-1 LTR promoter
directed gene expression with no effect on cell viability
(Ashraf, 2018). Curcumin had moderate effectiveness towards
Plasmodium falciparum and Leishmania organisms.
The ethanol extracts exhibit anti-Entamoeba histolytica
activity while curcumin has anti-P. falciparum and
anti-Leishmania effect in vitro. Curcumin seems to have
its antiviral activity for Epstein–Barr virus and HIV (Taher et
al., 2003). An extract of C. longa in both aqueous and ethanol
is used in aquaculture as a treatment for bacterial infections (Sahu
et al., 2005). Curcumin exerts anti-parasitic action against
African trypanosomes, has schistosomicidal activities against
Schistosoma mansoni adult worms, and has anti-malarial
in addition to nematocidal effects. Curcumin has shown a wide
range of antiviral activity against different viral models.
Similar to these reports, our findings indicated that curcumin
inhibits SARS-CoV-2 D614G strain which contains the most
widespread amino acid change (D614G in the spike protein)
carried by more than 99% of the prevalent variants since the
beginning of 2020. According to previous reports, curcumin
exhibited moderate selectivity for pre-infection and
post-infection treatment strategies. Contrarily, low selectivity
was obtained for pre–post infection treatment and co-treatment
strategies. Curcumin inhibited SARS-CoV-2 D614G strain by
pre-infection treatment of Vero E6 cells. This effect has also
been observed with other enveloped viruses such as Influenza,
Dengue, Zika, Chikungunya, Japanese encephalitis, Pseudorabies,
and Vesicular stomatitis virus, showing that curcumin treatment
affects the early stages of the replicative cycle, such as viral
attachment, internalization, fusion, or decapsidation. With
regard to SARS-CoV-2, spike protein binds to its human receptor
ACE2 (angiotensin-converting enzyme 2) through its
receptor-binding domain. Previous studies have reported a
favorable binding affinity of curcumin to the spike protein and
its cell receptor, ACE2 (angiotensin-converting enzyme).
According to the above, it could be suggested that curcumin
prevents the recognition of the target cell and subsequent
SARS-CoV-2 entry by direct interaction with cell factors or
viral proteins. This effect could be related to our results
obtained by co-treatment which suggest a possible virucidal
activity of curcumin against SARS-CoV-2 D614G strain. It has been demonstrated
that curcumin as a plant derivative has a wide range of
antiviral activity against a variety of viruses including
parainfluenza virus type 3 (PIV-3), feline infectious
peritonitis virus (FIPV), vesicular stomatitis virus (VSV),
herpes simplex virus (HSV), flock house virus (FHV), and
respiratory syncytial virus (RSV) assessed by MTT test showed
the potent antiviral activity of curcumin and its bioconjugates
against different viral pathogens for further studies. Curcumin
showed the anti-influenza activity against influenza viruses
PR8, H1N1, and H6N1. The results showed more than 90% reduction
in virus yield in cell culture using 30 μM of curcumin. In H1N1
and also H6N1 subtypes, the inhibition of haemagglutinin
interaction reflected the direct effect of curcumin on
infectivity of viral particles and this has proved by time of
drug addiction experiment. Additionally, unlike amantadine,
viruses developed no resistance to curcumin. There are
several studies illustrate that curcumin can impede viral
replication and prevent injuries caused by several virus
infectious diseases in particular, for RNA virus infections. In
vitro and in vivo results have shown that curcumin effectively
moderates infections and symptoms caused by the hepatitis virus,
respiratory syncytial virus (RSV), Human Immunodeficiency Virus
(HIV/AIDS), Zika virus, Chikungunya virus, Epstein Barr
virus, papilloma virus (HPV), enterovirus (enterovirus),
Japanese encephalitis virus, influenza virus, dengue virus, and
coronavirus (such as SARS-COVID 19) In recent studies that have
calculated and simulated molecular docking models for viral
infections, the results showed that the curcumin molecule can
directly interact with proteins of Ebola virus, influenza virus,
AIDS Viruses, dengue virus, and human papillomavirus (HPV), etc.
The combination of curcumin with viral coat proteins,
virus-specific enzymes, or RNA polymerase can affect and abolish
virus replication, infection, and damage to cells. Current
research results show that turmeric can inhibit SARS and COVID
19 infections via molecular binding, and currently curcumin is
also applied in clinical trial on COVID 19 infection. Antimicrobial activities for curcumin and rhizome
extract of C. longa against different bacteria, viruses,
fungi, and parasites have been reported. The promising results
for antimicrobial activity of curcumin made it a good candidate
to enhance the inhibitory effect of existing antimicrobial
agents. Curcumin has shown antibacterial activity effectively
against Staphylococcus aureus, Salmonella paratyphi,
Trichophyton gypseum, and Mycobacterium tuberculosis. The
antibacterial activity of the aqueous extracts from turmeric is
believed to be due to the anionic constituents like nitrate,
sulphates, chlorides, and thiocyanate. Antibacterial activity of curcumin was also studied
in endodontic bacteria Streptococcus mutans, Actinomyces
viscosus, Lactobacillus casei, Porphyromonas gingivalis,
Prevotella intermedia, and Enterococcus faecalis, and a
significant inhibition of bacterial growth was observed. Many
studies have revealed that curcumin and turmeric extracts
inhibit the growth of microorganisms. Curcumin has antibacterial
effects on both gram-positive and -negative bacteria, such as:
Staphylococcus aureus, Streptococcus pneumoniae, Salmonella,
Escherichia coli, Helicobacter pylori, etc., which often cause
human infectious diseases. In preclinical and clinical studies
for sepsis treatment, i.e. systemic bacterial infections,
curcumin can act on PI3K/AKT, NFκB, TNF-α and TGF-β1 pathways to
attenuate the toxicity of LPS on sepsis and curcumin also exerts
the protective role in the lungs, liver, and kidneys while
reducing the sequelae of tissue fibrosis after sepsis.
Curcumin is very effective against several pathogenic Gram +ve
bacteria such as Staphylococcus aureus, Staphylococcus
epidermidis and Enterococcus species that cause many infections
such as skin problems, pneumonia, meningitis, and urinary tract
infection. The study of curcumin against 14 strains of Candida
including 4 ATCC strains and 10 clinical isolates showed that
curcumin is a potent fungicide compound against Candida species
with MIC values range from 250 to 2000 μg/mL. In another study,
anti-Candida activity of curcumin was demonstrated against 38
different strains of Candida. A recent study revealed that,
curcumin exhibited in vitro antibacterial activity against most
prevalent organisms like Enterococcus faecalis, Prevotella intermedia, Porphyromonas gingivalis, Actinomyces viscosus,
Lactobacillus casei, Streptococcus mutans and Aggregatibacter
actinomycetemcomitans (Mandroli and Bhat 2013). Moreover,
curcumin demonstrated its effectiveness against Bacillus
subtilis, Mycobacterium tuberculosis, Escherichia coli,
Helicobacter pylori, Staphylococcus intermedius, Sarcina
lutea, Sarcina lutea and Neiserria gonorrhoeae (Tyagi et al.
2015; Marathe et al. 2011). Curcumin treatment reduced growth of
gut microbiota like Bifidobacterium, E.
faecalis, Bifidobacterium. pseudocatenulatum G4, Bifidobacterium.
longum BB536,E. coli K-12, Lactobacillus acidophilus and
Lactobacillus casei thereby inducing the susceptibility to
infectious disease (Marathe et al. 2011). Curcumin inhibited the
growth of both Gram-negative and Gram-positive bacteria.
Curcumin effectively reduced the infectious disease caused by
various species of Staphylococcus aureus (Tong et al.
2015;Teowetal.2016). Mechanistically, curcumin interfere with
quorum sensing, virulence and biofilm initiation, and inhibits
bacterial cell by suppressing its dynamic assembly. Curcumin
demonstrated its effectiveness against parasites like
Trypanosoma, Plasmodium and Giardia. In parasites culture,
curcumin treatment induced DNA damage via its prooxidant
activity and inhibited histone acetyltransferases in
Plasmodium falciparum resulted in cytotoxicity, which can
be targeted for treatment of malaria (Cui, Miao, and Cui 2007),
revealing its therapeutic potential against cerebral malaria as
adjunctive therapy (Mimche, Taramelli, and Vivas 2011). Curcumin
induced DNA damage and apoptosis and effectively inhibited the
growth of Giardia lamblia (Perez-Arriaga et al. 2006).
Moreover, curcumin administration mediates anti-parasitic
activity against Trypanosoma, a parasite which is
responsible for sleeping sickness and Chagas disease (Marathe et
al. 2011). The biological effect of curcumin to reduce these
infections is mainly due to its pro-oxidant and apoptotic
activities, therefore, it can be recommended as a novel drug for
management of giardia, trypanosoma and plasmodium
infections. Curcumin treatment upregulated the transcription of
chitin synthase-1, chitin synthase-3 and PKC in Sporothrix
schenckii thus reduced virulence in infected mice (Huang et
al. 2016a). Curcumin induced photodynamic inactivation of the
fungus Candida albicans in murine model of oral
candidiasis (Dovigo et al. 2013). Also, curcumin exhibited
therapeutic potential against oropharyngeal candidiasis in a
mouse model (Karaman et al. 2011). In fungal cell cultures,
curcumin inhibited the growth of wide range of pathogenic fungus
that includes Aspergillus clavatus, Aspergillus terreus,
Aspergillus tamarii, Aspergillus fumigatus, Aspergillus flavus
IMI190443, Aspergillus nomius ATCC 15546, Aspergillus
fumigatus ATCC 16913, Paracoccidioides brasiliensis B339,
Paracoccidioides brasiliensis MG04, Paracoccidioides
brasiliensis 17, Paracoccidioides brasiliensis 608,
Paracoccidioides brasiliensis Pb18, Paracoccidioides
brasiliensis Pb01, Paracoccidioides brasiliensis MG05,
Sporothrix schenckii ATCC 10212, Cryptococcus neoformans ATCC
32608, Candida dubliniensis (Cd28), Candida dubliniensis (Cd22),
Candida glabrata ATCC 2001, Candida parapsilosis ATCC 20019,
Candida krusei ATCC 20298, Candida tropicalis ATCC 750 and
Candida albicans ATCC 18804 (Martins et al. 2008). Curcumin
(500 mg/L) also exhibited antifungal effects against
Phytophthora infestans, Pu. Recondite and Rhizoctonia
solani (Kim, Choi, and Lee 2003). Curcumin demonstrated
fungicidal activity against the clinical isolates of Candida
species like Candida tropicalis, Candida kefyr, Candida
krusei, Candida guilliermondii, Candida glabrata, Candida
parapsilosis and Candida albicans at MIC value of
32–128 mg/mL (Zorofchian Moghadamtousi et al. 2014). The
suggested anti-fungal mechanisms of curcumin includes the
leakage of intracellular component through the flappy membrane,
disruption of fungal plasma membrane, generation of oxidative
stress, induction of early apoptosis, inhibition hyphae
development, upregulation of chitin synthase and PKC etc. (Lee
and Lee 2014; Sharma et al. 2010). These evidences on the
mechanistic action of curcumin could be employed in improving
the treatment strategies for fungal infections. A recent study
has shown that the anti-inflammatory and anti-oxidant effects
conferred by curcumin protect from human cytomegalovirus
infection in Balb/c mice (Lv et al. 2014). Among various
phytochemicals evaluated for antiviral activity against
norovirus, curcumin exhibited most potent anti-noroviral
effects. In a cell culture infection model, curcumin exposure
for 3 days was found to reduce norovirus infectivity by 91%.
Thus, curcumin might be a promising anti-noroviral candidate to
prevent foodborne illness (Yang et al. 2016). Curcumin
demonstrated promising anti-influenza activity against influenza
viruses PR8, H1N1 and H6N1 by interfering with viral
hemagglutination activity (Chen et al. 2010; Dao et al. 2012; Ou
et al. 2013). In dengue infected BHK-21 cells, curcumin
administration reduced the number of plaques produced,
intracellular accumulation of viral proteins and increased the
level of Lys48 ubiquitin-conjugated proteins in dengue virus
(Padilla-S et al. 2014). In in vitro assays, curcumin
demonstrated potent antiviral effect against Human enterovirus
71 (EV71). Curcumin inhibited viral RNA synthesis and expression
of viral protein, thereby decreasing production of viral progeny
(Qin et al. 2014). Proteomics analysis indicated that curcumin
(15–240 lM) pretreatment exert antiviral activity by
downregulating heat shock cognate 71 and inhibited the
replication of viral hemorrhagic septicemia virus (Jeong et al.
2015). On the other hand, curcumin exhibited remarkable
antiviral effects against herpes simplex virus type 1 (HSV-1) by
blocking the recruitment of RNA polymerase II and expression of
viral immediate-early genes (Kutluay et al. 2008). In another
study, curcumin and its metallo derivatives, viz.
gallium-curcumin and Cu-curcumin also exhibited remarkable
anti-HSV-1 activity in vitro (Zandi et al. 2010). Moreover,
curcumin administration conferred significant protection against
intra-vaginal HSV-2 infection (Bourne et al. 1999). Curcumin
inhibited both HIV-1 (IC 50 -100mM) and HIV-2 protease (IC 50
-250mM) thereby suppressed the replication of viral genes and
prevent multiplicity of HIV (Sui et al. 1993). Curcumin mediated
inhibition of HIV protease and integrase (IC 50 40 mM) resulted
in anti-retroviral activity (Mazumder et al. 1997; Mazumder et
al. 1995). Curcumin induced anti-HIV activity can be attributed
to degradation of Tat via proteosomal pathway and inhibition of
Tat protein acetylation by p300/CREB-binding
protein thereby sup- pressed HIV-1 multiplication (Ali and
Banerjea 2016; Balasubramanyam et al. 2004). Curcumin
demonstrated strong anti-HPV activity in cervical and oral
cancer cells through downregulation of HPV oncogene expression
(E6 and E7) of highly oncogenic HPV, HPV-16 and HPV-18 (Divya
and Pillai 2006; Mishra and Das 2015; Prusty and Das 2005).
Curcumin downregulated the transcription factor, AP-1 in HeLa
cells which is critical for transcription of HPV-16 and HPV-18
(Prusty and Das 2005). Curcumin mediated downregulation of viral
oncogenes is attributed to its ability to modulate apoptosis and
prevent NFkB and AP- 1 translocation thereby suppressing the
transcription of HPVs (Divya and Pillai 2006; Prusty and Das
2005). Curcumin exhibited potent antiviral effect against
coxsackie virus by inhibiting viral replication, RNA expression
and protein synthesis via ubiquitin-proteasome system mediated
protein modification or degradation (Si et al. 2005; Si et al.
2007). Mechanistically, curcumin treatment downregulated JunD
protein, reduced production of infective viral particles,
downregulated genomic transcription and translation, inhibited
viral oncoproteins E6 and E7 expressions, suppressed the
Akt/sterol regulatory element-binding proteins (SREBP)- 1
pathway, increased p53 level, inhibited hemagglutination,
inhibited proteases, integrase and Tat protein acetylation
(Zorofchian Moghadamtousi et al. 2014; Mazumder et al. 1995;
Balasubramanyam et al. 2004; Dutta, Ghosh, and Basu 2009). The
extensive research on antiviral activities of curcumin against
different viral pathogens nominates this compound as a potent
antiviral drug candidate.
Effect of Curcumin on
COVID-19 | Curcumin, a natural compound with
anti-inflammatory effect, could as an adjuvant drug in COVID-19
treatment. Curcumin has been revealed to be linked to the viral
S1 protein, which is required for SARS-CoV-2 entry in an in
silico approach; thus, it may inhibit cytokine storm in the
severe stage of COVID-19 (Pawitan, 2020). Curcumin can inhibit SARS-CoV replication. Several studies suggest that curcumin can
inhibit SARS-CoV-2 replication. Evidence has already emerged
regarding the action of curcumin in SARS-associated corona virus
(SARS CO-V) by directly interacting with viral proteins,
disrupting the viral envelope, inhibiting viral proteases and
modulating NFKB, Nrf2 and high mobility group box 1(HMGB1)
pathways in vitro. SARS-CoV-2 (COVID-19) has nearly 79%
resemblance to SARS CO-V and hence the postulation. Curcumin can block the
interaction between the spike glycoprotein and
angiotensin-converting enzyme 2 (ACE2) and inhibit the Nsp15
protein, therefore blocking replication of the virus or
inhibiting viral protease. These observations were supported by
a study by Han et al. who demonstrated that curcumin strongly
inhibited TGEV proliferation and viral protein expression in a
dose and time-dependent manner, and treatment with curcumin
caused a reduction in both viral particles (IC50 of 8.6 μM) and
protein levels in porcine kidney cells. This study suggested
that curcumin may inhibit the adsorption of TGEV or that it
possesses excellent virucidal activity. Compared to the placebo group,
curcumin could reduce the frequency of Th17 cells, Treg and
their related inflammatory factors in both mild and severe
COVID‐19 patients. In addition to anti-inflammatory effect,
curcumin can also play an antiviral role by inhibiting
SARS-CoV-2 entry into cells and inhibiting viral proliferation.
Curcumin has a variety of pharmacological effects and high
safety, which makes it an adjunctive drug for the treatment of
COVID-19. In a clinical trial, orally administered curcumin with
piperine as adjuvant therapy in COVID-19 treatment could
substantially reduce morbidity and mortality, and improve
clinical symptoms. Curcumin effectively neutralized
SARS-CoV-2 at subtoxic concentrations in Vero E6 and human
Calu-3 cells. Furthermore, curcumin treatment significantly
reduced SARS-CoV-2 RNA levels in cell culture supernatants. This
data uncovers curcumin as a promising compound for complementary
COVID-19 treatment. Curcumin concentrations contained in
turmeric root or capsules used as nutritional supplements
completely neutralized SARS-CoV-2 in vitro. Due to the antiviral
as well as anti-inflammatory effect of curcumin, the compound
might have a positive effect on COVID-19 progression. Curcumin
potently neutralizes SARS-CoV-2 in vitro at low subtoxic
concentrations. The good safety profile of curcumin and its
immunomodulatory as well as the antiviral effect make curcumin a
promising candidate for complementary treatment of COVID-19. |
|
How may Curcumin work against depression, major depressive
disorder, and anxiety? |
Curcumin has a wide range of
characteristics that are important to depression pathogenesis.
The extract prevented the decrease in serotonin, noradrenalin,
and dopamine concentrations while increasing serotonin turnover,
cortisol levels, and serum corticotrophin-releasing factor
levels (Xia et al., 2007). The consequences of orally
administered curcumin seem on behavior under chronic stress or
depression condition in the rat model. Curcumin administration
showed a similar impact to imipramine, a known antidepressant
drug, and it has been indicated by various authors to be a
feasible alternative source in depression condition (Mohammed et
al., 2019; Qi et al., 2020). Curcumin has anti-inflammatory,
antioxidant and neurotrophic properties, suggesting it has
strong potential for relieving depression. Curcumin’s
anti-inflammatory effect is one reason for its improvement in
depression. In addition to its anti-inflammatory properties,
curcumin also inhibits the release of monoamine oxidase,
serotonin and dopamine, and regulates the hypothalamus pituitary
adrenal axis, neurotrophic factors, and hippocampal neurogenesis
and neuroplasticity. Administration of curcumin decrease mRNA
expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α,
through down-regulation IL-1β/NF-κB signaling,105 inhibit the
NLRP3 inflammasome activation. Curcumin improves IL-1β-induced
neuronal apoptosis by inhibiting the P38 pathway In a
meta-analysis of nine clinical trials, curcumin may improve
symptoms of depression and anxiety in patients with depression.
In randomized double-blind, placebo-controlled trial, adjuvant
curcumin (doses increased from 500 mg/day to 1500 mg/day) showed
a significant difference between curcumin and placebo at weeks
12 and 16. The core issue of depression has been identified as
inflammation, and
curcumin has been found to be comparable to prescription antidepressant
drugs. In
one study published in
Phytotherapy Research,
scientists studied 60 patients with serious depression over a six-week trial
and found that turmeric was as effective at treating depression as Prozac.
This randomized control trial took 60 volunteers diagnosed
with major depressive disorder and compared the effect of
curcumin to fluoxetine (Prozac). Researchers discovered that the
principal curcuminoid in turmeric is not only as effective as Prozac in
managing depression, but it doesn’t carry with it all the dangerous side
effects as anti-depressive drugs do. One-third of the participants in the
study were given 20 mg of fluoxetine (which is sold under the prescription
names Prozac and Sarafem), one-third were given 1,000 mg of curcumin (the
active ingredient in turmeric), and one one-third were given a combination
of both. "Curcumin, an active ingredient of Curcuma longa
(Zingiberaceae), has shown potential antidepressant-like activity in animal
studies,” the researchers wrote. “The objectives of this trial were to
compare the efficacy and safety of curcumin with fluoxetine in patients with
Major Depressive Disorder (MDD).” They concluded that curcumin was “well
tolerated” by all the patients. All three groups showed approximately equal
improvement in their depression, whether they were taking the turmeric, the
antidepressant or a combination of both.“This study provides first clinical
evidence that curcumin may be used as an effective and safe modality for
treatment in patients with MDD without concurrent suicidal ideation or other
psychotic disorders. Curcumin, a natural compound derived from the herb Curcuma longa, exhibits a wide range of pharmacological
properties and thus has been considered as a potent
antidepressant drug. Curcumin may exhibit multiple
antidepressant activities: (a) modulating the neurotransmitter
levels including DA, NE, 5‐HIAA and inhibiting the expression of
monoamine oxidase enzymes; (b) reducing the inflammatory
response by regulating the production of pro‐inflammatory
markers; (c) repairing neurodegeneration and enhancing
neurogenesis and neuronal plasticity typically increased BDNF
levels; (d) improving the activities of antioxidant enzymes; (e)
decreasing the nitric oxide levels; (f) regulating mitochondrial
disturbances; and (g) moderating hypothalamus‐pituitary‐adrenal
(HPA) disturbances. The multiple mechanisms of curcumin provide
a unique advantage in the medication of depression, especially
in the term of adverse effects. A new
study, published online ahead of print in the
Journal of Affective
Disorders, finds that the spice curcumin, a derivative of turmeric, may
be an effective treatment for depression. The study was a randomized,
placebo-controlled trial (the gold standard methodology for medication
studies). The researchers found that curcumin was better than a placebo
treatment, and those with atypical depression were far more likely to
improve. The use of curcumin appeared especially effective for those with
atypical depression. Atypical depression, despite its name, is relatively
common (around 40% of MDD cases). The “atypical” moniker refers to its
particular features: excessive sleep, weight gain, mood improvement in
response to positive events, heavy, immovable feelings in the limbs, and
interpersonal rejection sensitivity. Atypical depression is considered to
have a more chronic course, with worse outcomes overall, so the potential
for a viable treatment with fewer side effects than current medications
provides hope for an improved prognosis. Previous
studies have shown evidence that curcumin could be an
effective
treatment for
depression and found minimal side effects. This study adds to the
literature by comparing several doses of curcumin as well as a
curcumin/saffron combination treatment. A study published in Brain Research examined the effects of
curcumin administration to laboratory rats after exposure to a chronic
stress protocol. Researchers found that curcumin supplementation had a
beneficial effect on
reducing stress-related symptoms of depression.
A study in Psychopharmacology showed curcumin
increased serotonin production and had an antidepressant effect on
laboratory mice exposed to several lab tests. In a six-week, randomized,
single-blinded, placebo-controlled study in 60 MDD patients, supplemental
curcumin (~880 mg/day of curcuminoids) alone yielded a similar response rate
to the antidepressant, fluoxetine (a serotonin reuptake inhibitor [Prozac];
20 mg/day) in terms of depressive symptoms. A 2009 review published in Scientific World Journal
hypothesizes that curcumin from turmeric may provide benefits for
depression by
assisting with the regulation of brain neurotransmitters like
dopamine and serotonin and inhibiting the monoamine oxidase enzyme, which
plays a role in breaking down these neurotransmitters. The
neurotransmitters are also what Prozac treats, helping serotonin be used
effectively by the brain. Major depressive
disorder (MDD) is a neuropsychiatric disorder associated with abnormal
neurotransmission; it is primarily treated with drugs that improve the
bioavailability of neurotransmitters like serotonin, noradrenaline, and
dopamine in the brain. Characteristics of MDD also include alterations
in the hypothalamus-pituitary-adrenal axis, increased neuroinflammation,
defective neurogenesis, and neuronal death. A few clinical studies have
examined the effect of curcumin alone or with conventional
antidepressant drugs in MDD patients. A recent meta-analysis of six
randomized controlled trials found that supplementation with curcumin
significantly reduced depression symptoms. Moreover, in a randomized controlled study in 100 participants taking
escitalopram (a serotonin reuptake inhibitor [Lexapro]; 5 to 15 mg/week),
supplemental curcumin (1,000 mg/day) for six weeks increased the
antidepressant effect of the medication. Curcumin also induced a reduction
in plasma concentrations of inflammatory markers and an increase in plasma
concentrations of brain-derived neurotrophic factor compared to placebo
(antidepressant drug alone).
A
study involving 56 people with major depressive disorder
revealed that 500 mg of curcumin taken twice a day for eight
weeks could ease mood-related symptoms. In a controlled
trial, 60 people with depression were randomized into three
groups. One group took Prozac, another group one gram of
curcumin and the third group both Prozac and curcumin. After 6
weeks, curcumin had led to improvements that were similar to
Prozac. The group that took both Prozac and curcumin fared best.
According to this small study, curcumin is as effective as an
antidepressant. Depression is also linked to reduced levels of
brain-derived neurotrophic factor (BDNF) and a shrinking
hippocampus, a brain area with a role in learning and memory.
Curcumin boosts BDNF levels, potentially reversing some of these
changes. There is also some evidence that curcumin can boost the
brain neurotransmitters serotonin and dopamine. A study
published in the journal Acta Poloniae Pharmaceutica found that
curcumin compared favorably to both drugs in reducing depressive
behavior in an animal model. Depression and anxiety are
different neurological disorders, but depressive patients often
experience symptoms like anxiety disorder, such as irritability,
nervousness, and problems in concentrating and sleeping.
Depression and anxiety disorders have its own pathophysiology as
well as behavioral and emotional symptoms. In a double blind,
cross-over clinical trial, curcumin administration (1 g/day for
30 days) significantly reduced anxiety like behavior. Chronic
curcumin administration (500 mg, twice daily for eight weeks) is
associated with elevated urinary level of substance P and
thromboxane B2 as compared to the placebo group. In addition,
curcumin administration ameliorated the plasma endothelin-1 and
leptin which is associated with greater reductions in IDS-SR30,
a major depressive episode (Lopresti et al. 2015). In a
randomized, double-blind, placebo-controlled trial, curcumin
treatment (500 mg twice daily) for 4 to 8 week provides partial
improvement in people with major depressive disorder (Lopresti
et al. 2014). A recent meta-analysis data suggest that, curcumin
supplementation appears to be efficacious, safe and
well-tolerated anti-depressant and anxiolytic in patients (Ng et
al. 2017). In animal study, curcumin treatment is reported to
attenuate depressive phenotype during chronically stressed
condition via several mechanisms viz., reduction in adrenal
gland to body weight ratio, reduction in serum corticosterone
level, reduction in adrenal cortex thickness as well as
upregulation of BDNF and COX-2 expression and reduction in
(pCREB/ CREB) levels in brain. Curcumin administration increased
the level of synaptophysin and BDNF in amygdala alongside
reduced depressive like behavior in chronically stressed rats
(Zhang et al. 2014). Curcumin treatment is known to inhibit the
release of glutamate in synaptosome and induce activation of
GluN2B N-methyl-D-aspartate receptor (NMDAR) subunits resulting
in antidepressant like action (Zhang et al. 2013c; Lin et al.). Curcumin administration significantly reduced anxiety
like effect in ovariectomized (Morrone et al. 2016) and stressed
rats (Haider et al. 2015). The general mechanism of action of
curcumin treatment includes, inhibition of brain monoamine
oxidase (MAO)-A/ B activity, modulation of serotonin receptor,
amelioration of brain dopamine, serotonin and noradrenaline
levels, increase the neurotrophic factor, enhance neuronal
growth, increase neuroprotection, reduce neuroinflammation,
apoptosis and oxidative stress (Lopresti 2017; Choi et al.
2017).
|
|
How may
Curcumin work as an antioxidant? |
The chemical structure of curcumin
gives it a powerful antioxidant capacity, which is 2.75 times
that of vitamin C and 1.6 times that of vitamin E.
Curcumin can help the body rid itself of hydroxyl radicals,
singlet oxygen, superoxide radicals, nitrogen dioxide, and NO.
Curcumin pretreatment was proven to reduce ischemia-induced
mutations in the heart (Dikshit et al.). The efficiency of
curcumin on endothelial heme oxygenase-1 (inducible stress
protein) employing bovine aortic endothelial cells was
discovered in an in vitro investigation that resulted in
increased cellular resistance to oxidative stress. Curcumin can
also help Caenorhabditis elegans live longer by lowering
intracellular ROS and lipofuscin levels during aging (Liao et
al., 2011). Previous research into the potential of C. longa to
sustain hippocampal cells of male Wistar rats from lead-induced
damage and reduces lipid peroxidation caused by toxic heavy
metals. Resveratrol and curcumin alleviate and synergistically
repair oxidative stress to the tissues by enhancing antioxidant
response through free radical scavenging (Al-Basher et al.,
2020). In one of the earlier studies, the anti-inflammatory and
antioxidant capability of curcumin was detected to be
synergistically enhanced with quercetin, and a synergistic
protective effect was also demonstrated in diazinon-induced rats
(Abdel-Diam et al., 2019). The anti-inflammatory impact of
berberine and curcumin may decrease oxidative stress, liver
inflammation, and lipid metabolism (Feng et al., 2018), and the
berberine combination also reduced inflammatory and oxidative
stress responses in the cortex and hippocampus of rats (Lin et
al., 2020). Antioxidant
and anti-inflammatory properties are the two primary mechanisms
that explain the majority of the effects of curcumin on the
various conditions. The anti-oxidative action of curcumin is
mediated through inhibition of stress-induced elevated levels of
8-hydroxydeoxyguanosine and 8-nitroguanine, regulating the
activity of mitochondrial respiratory complexes and upregulation
of Nrf2 (nuclear factor erythroid-derived 2-related factor 2)
that induces haemoxygenase-1 (HO-1) The anti-oxidant activity of
curcumin is predominantly due to the hydroxyl group. Curcumin
(5,10,20 and 30 µM) stimulates the expression of Nrf2 in a
concentration- and time-dependent manner, which in turn
increases HO-1 expression and HO-1 activity, which is a
redox-sensitive inducible protein that protects from various
forms of stress in cultured renal epithelial cells from rats. It
stimulates ARE (antioxidant responsive elements) binding
activity in NRK cells from rat kidney. Sreejayan et al. showed
that curcumin at a dose of 25 µM reduced nitrite production from
incubated solution of sodium nitroprusside in phosphate-buffered
saline. The scavenging of nitric oxide (NO) by curcumin was
concentration-dependent (50% at 20.4 and 100% at 50 µM).
Curcumin was shown not to interact with nitrite detection assay
or directly interact with nitrite. All forms of curcumin—demethoxy
curcumin, bisdemethoxy curcumin and diacetyl curcumin—had NO
scavenging property irrespective of the methoxy or the phenolic
group.Curcumin has also been shown to improve systemic
markers of oxidative stress. There is evidence that it can
increase serum activities of antioxidants such as superoxide
dismutase (SOD). A recent systematic review and meta-analysis of
randomized control data related to the efficacy of
supplementation with purified curcuminoids on oxidative stress
parameters—indicated a significant effect of curcuminoids
supplementation on all investigated parameters of oxidative
stress including plasma activities of SOD and catalase, as well
as serum concentrations of glutathione peroxidase (GSH) and
lipid peroxides. It is noteworthy to point out that all of the
studies included in the meta-analysis utilized some sort of
formulation to overcome bioavailability challenges, and four out
of the six used piperine. Curcumin’s effect on free radicals is
carried out by several different mechanisms. It can scavenge
different forms of free radicals, such as reactive oxygen and
nitrogen species (ROS and RNS, respectively); it can modulate
the activity of GSH, catalase, and SOD enzymes active in the
neutralization of free radicals; also, it can inhibit
ROS-generating enzymes such as lipoxygenase/cyclooxygenase and
xanthine hydrogenase/oxidase. In addition, curcumin is a
lipophilic compound, which makes it an efficient scavenger of
peroxyl radicals, therefore, like vitamin E, curcumin is also
considered as a chain-breaking antioxidant. Curcumin can
be served as a free radical scavenger in the body and also
promotes the endogenous antioxidant glutathione (GSH) synthesis
to protect cells or tissues from free radical injury. In vitro
cell and animal experiments also show that curcumin can enhance
the activity of superoxidase dismutase (SOD) and increase GSH
levels in cells and serum as well. In preclinical studies and
clinical trial, when the body organs or tissues become ischemia
due to the temporary interruption of blood circulation, such as
stroke, myocardial infarction, surgery, or transplantation,
etc.. After restoring blood flow, those ischemic reperfusion
tissues often produce excessive free radicals and cause
oxidative stress and injury. Administration of curcumin can
scavenge free radicals; thereby, reducing the damage of free
radicals to tissue cells, which also reduces damage caused by
excessive inflammation of tissues. Remarkably, investigating the role of
natural substances such as curcumin or derivatives with high
antioxidant potential that counteract oxidative stress seems to
be an effective preventive measure against free radical-linked
aging. Due to its chemical structure, curcumin has proved to be
an excellent scavenger of ROS and reactive nitrogen species and
is able to attenuate or prevent the exercise-induced oxidative
stress and inflammation, by modulation of GSH, catalase, and SOD
enzymes and inhibiting of ROS-generating enzymes such as
lipoxygenase / cyclooxygenase and xanthine hydrogenase/oxidase.
This has strengthened our conviction that curcumin is the golden
nutraceutical with proven potential in preventing/delaying the
onset of age-related diseases. Curcumin displays potent
biological and pharmacological effects on renal health. Aging is
an independent risk factor increasing the likelihood of
developing cardiovascular diseases which is due primarily to the
arteries remodeling and the development of vascular endothelial
dysfunction. Another promising anti-aging potential of curcumin
supplementation was shown in healthy middle-aged older men and
postmenopausal women. Indeed, 12 weeks curcumin administration
has improved resistance artery endothelial function by
increasing NO bioavailability and reducing vascular oxidative
stress. This suggests the critical role of curcumin to maintain
health vascular endothelium with aging, a fundamental element in
the prevention of atherosclerosis and arterial diseases. Another
study provides additional support about the role of curcumin
associated with aging in patients at risk of cardiovascular
diseases through reducing serum LDL-cholesterol and triglyceride
levels. Determining the long-term benefits of curcumin in patients
with cardiovascular diseases or at risk to develop
cardiovascular disorders seems like a promising research
avenue. The accelerated aging induced by oxidative stress
results in sex-specific differences in longevity and
susceptibility to age-related neurodegeneration. In a
previous research, curcumin was shown to prolong lifespan of
fruit fly model (Drosophila
melanogaster) through enhancing SOD activity.
These findings were corroborated by other data where
curcumin induced sex-specific in vivo responses to oxidative
stress. This includes protection from hydrogen peroxide and
alterations in behavior of
Drosophila melanogaster. This may rely on gene
expression and support the anti-aging role of curcumin in
gender-dependent manner. Curcumin belongs to the class of
hormetic agents that stabilize Nrf2 and enhance expression of
HO-1. Curcumin triggers Nrf2 pathway, which has a pivotal role
in activating antioxidant enzymes, such as thioredoxin
reductase, Hsp70, sirtuins. Furthermore, another study finding
reported that curcumin increased the activity of several
antioxidant enzymes including protein thiol, non-protein thiol,
GPx, and SOD in dogs fed with curcumin on day 30 compared with
control dogs. In addition, curcumin consumption stimulated the
antioxidant capacity in the serum of dogs and consequently
reducing ROS levels. Curcumin improved animal health, with
particular emphasis on the stimulation of the antioxidant system
and evidence of an anti-inflammatory effect. This suggested that
curcumin exerts beneficial effect on both growth, health and
consequently slowing down aging.
Curcumin supplementation accompanied with regular physical
exercise could potentially slowing down aging and/or preventing
oxidative stress-induced age-related functional and structural
changes and the age-related disorders. Collectively, these
findings reinforce the antioxidant potential of curcumin on
organ health function in the context of aging. Further
investigations are warranted to unravel the exact molecular
targets and signaling pathways responsible for the antioxidant
effects of curcumin in different human populations. |
|
How may Curcumin work
against retinal diseases such as uveitis, Diabetic retinopathy, and
Age-related macular degeneration? |
|
Effect of Curcumin on Uveitis |
Curcumin administration attenuated the degenerative and
inflammatory conditions associated with eye like uveitis.
Corticosteroids are normally used for treatment of uveitis.
However, the adverse effects associated with these drugs limit
their use. One study evaluated the efficacy of curcumin against
chronic anterior uveitis. Curcumin was administered orally to
patients with chronic anterior uveitis at a dose of 375 mg three
times a day for 12 weeks. All patients who received
curcumin alone exhibited improvement, the group receiving
anti-tubercular therapy along with curcumin had a response rate
of 86%. Furthermore, follow-up of all patients for the next 3
years found recurrence rates of 55% for the first group and 36%
for the second group. The efficacy of curcumin on
recurrences after treatment was comparable to that of
corticosteroid therapy. Furthermore, lack of any adverse effects
with curcumin was an advantage over corticosteroid therapy.
Thus, the study demonstrated the therapeutic role of curcumin
and its efficacy against recurrent anterior uveitis. Effect of Curcumin on
Diabetic Retinopathy | Retina, because of its high
content of polyunsaturated fatty acids (PUFA), high oxygen and
glucose uptake is, vulnerable to oxidative stress. Inflammation
is another underlying factor in the pathogenesis of diabetic
retinopathy . Oxidative stress leads to formation of ROS, which
is hypothesized to cause the development of neuropathy,
nephropathy, myocardial infarction and retinopathy.
Autooxidation of glucose, shift in redox balance, decrease in
the concentration of reduced glutathione (GSH–ROS scavenger),
vitamin C, Beta carotene and vitamin E and impairment of
antioxidant enzymes like superoxide dismutase (SOD), glutathione
reductase, glutathione peroxidase and catalase are considered as
the possible sources of oxidative stress in diabetes. Retina of
diabetic rats shows elevated superoxide and hydrogen peroxide
(H2O2) levels along with lipid peroxidation and oxidative damage
to DNA because of ROS. The other pathways that lead to diabetic
retinopathy are polyol pathway that depletes nicotinamide
adenine dinucleotide phosphate (NADPH) essential for
regeneration of GSH, advanced glycosylation end product (AGE)
and its receptor RAGE that get deposited in the retinal
capillary cells leading to more ROS and activation of NFKB and
caspase-3-induced apoptosis and damage to cellular constituents,
protein kinase C (PKC) pathway, which gets activated by
increased ROS and diacylglycerol as a result of hyperglycaemia
that increase vessel permeability and blood flow, stimulate
neovascularization, endothelial proliferation and apoptosis by
regulating the action of vascular endothelial growth factor
(VEGF), insulin-like growth factor-1 (IGF-1) and transforming
growth factor-β (TGF-β). ROS also activates hexosamine pathway
by inhibiting glyceraldehyde-3-phosphate dehydrogenase (GAPDH),
which further activates AGE pathway and the damage thereafter.
ROS causes dysfunction of mitochondria, which leads to
superoxide production and free radical damage and mutations in
mitochondrial DNA that leads to mitochondrial DNA damage in
retina in diabetes. Also, ROS-induced damage to mitochondria
suppresses antioxidant-mediated effective scavenging of ROS.
Exposure of pericytes and endothelial cells shows an increase in
caspase-3 activity, oxidative stress and transcription factors
that leads to capillary cell death. Photoreceptors, Muller
cells, ganglion cells and astrocytes are affected and are
involved in the pathogenesis of diabetic retinopathy. Effect of Curcumin on
Age-related Macular Degeneration | Curcumin protected
against H2O2-induced cell death in a concentration of 10 µM when
pre-treatment time was less than 8–12 h. Curcumin reduced and
maintained intracellular ROS levels in age-related macular
degeneration-RPE cells at varied concentrations (0.1, 1, 10 µM)
for 12 h in H2O2-exposed cells. Treatment with curcumin showed
increase of anti-oxidant genes HO-1, SOD2 (superoxide dismutase
2) and GPX1 (glutathione peroxidase 1) and reduces the
expression of VEGF, PDGF (platelet-derived growth factor) and
IGFBP 2 (insulin-like growth factor binding protein 2) using
RTPCR in RPE-age-related macular degeneration cells.
Pre-treatment with curcumin inhibited JNK pathway that involves
a series of inflammatory pathways leading to cell death in
RPE-age-related macular degenerationcells. Thus, curcumin may
potentially be an ideal drug in restoring the function in
age-related macular degeneration patient-derived RPE cells. Park
et al. studied the protective effects of curcumin in
A2E-accumulated ARPE-19 cells that were exposed to blue light to
induce cytotoxicity. A2E and iso-A2E are main pigments of
lipofuscin that accumulate in RPE and cause RPE cell death in
age-related macular degeneration. |
|
How may Curcumin work
as an Anti-inflammatory? |
|
Chronic inflammation may be the engine that drives many of the
most feared illnesses of middle and old age. This concept
suggests a new and possibly much simpler way of warding off
disease. Instead of different treatments for, say, heart
disease, Alzheimer's and colon cancer, there might be a single,
inflammation-reducing remedy that would prevent all three.
Curcumin activity for inflammation after giving oral
administration was comparable to that of cortisone or
phenylbutazone. Curcumin reduced inflammatory swelling, this
effect resulted from inhibiting biosynthesis of inflammatory
prostaglandins from arachidonic acid and neutrophil function
during inflammatory states. A large number of studies have proved that curcumin
has a variety of biological activities, among which
anti-inflammatory effect is a significant feature of it. The physiological and pathological
mechanisms of inflammatory bowel disease, psoriasis,
atherosclerosis, COVID-19 and other research focus diseases are
not clear yet, and they are considered to be related to
inflammation. The anti-inflammatory effect of curcumin can
effectively improve the symptoms of these diseases. The
anti-inflammatory property of curcumin is by inhibition of
TNF-dependent NFkB (tumour necrosis factor-dependent
transcriptional nuclear factor kappa B) and pathways that
produce reactive oxygen intermediates. Curcumin downregulates
COX-2 (cyclooxygenase-2) that are predominantly seen at the
sites of inflammation that mediate pain and inflammatory
process. Curcumin is effective against inflammation and edema.
Curcumin is acceptable at large doses (12 g/day) in humans,
according to phase I clinical studies and has been shown to have
medicinal potential against a variety of human ailments,
particularly diabetes, cancer, arthritis, cardiovascular
disease, Crohn’s disease, and neurological disease.
Curcumin was evaluated for its anti-inflammatory potential in a
rat model for the treatment of osteoarthritis. Results suggested
that curcumin significantly reduced the expression of cytokine
levels in synovial fluid targeting the TLR4/NF-κB signaling
pathway. The effect of curcumin on inflammatory indices was
evaluated in a randomized control study. Results of the study
indicated an outstanding reduction in inflammation through
reduction in TNF-α, concluding that curcumin plays a key role in
inflammation suppression in hepatic patients with nonalcoholic
fatty liver disorders. The findings of another study revealed
that curcumin reduced the expression of IL-6, TNF-α, and the
NF-κB signaling pathway and reduced the rate of cell apoptosis
resulting in the healing of injured kidney cells. Apart from
individual therapy, curcumin in combination therapy has shown
significant anti-inflammatory action. In this regard,
hyperlipidemia-induced inflammation was targeted by the combined
delivery of curcumin and rutin in Wistar rats. Results of the
study showed an increase in HDL and a decrease in triglyceride
level after treatment with curcumin and rutin combined therapy.
It is concluded that curcumin has potential in treating
inflammation and can be used as a therapeutic medicament. Curcumin inhibits pro-inflammatory enzyme 5-LOX
(5-lipoxygenase) that are involved in the biosynthesis of
leukotrienes and lipid mediators of inflammation. It also
downregulates inflammatory cytokines like TNF, IL-1
(interleukin-1), IL-6, IL-8, iNOS (inducible nitric oxide
synthase) and interferon-ϒ. Curcumin at a dose of 360 mg/dose
for 3–4 months in humans reduced clinical relapse in those with
quiescent inflammatory bowel disease and decreased the use of
concomitant medications. This
inflammation theory explains how immune-system errors are
linked to more illnesses. Medical researchers are becoming
increasingly convinced that the most primitive part of the
immune system (inflammation), may play a crucial role in some of
the most devastating afflictions of modern humans, including
heart disease, cancer, diabetes and possibly Alzheimer's.
Study findings suggest that in the past, gene
variants rose in frequency in the human population to help
protect us against viruses, bacteria and other pathogens. But
now in our modern world, the environment and exposure to
pathogens has changed, and the genetic variants that were
originally meant to protect us, now make an autoimmune reaction
more likely. These results are consistent with the hygiene
hypothesis in which our cleaner environment is thought to
contribute to the increasing prevalence of inflammatory
diseases. While short-term inflammation in the body is a necessary component of a
functioning system, helping to fight off pathogenic invasion and repairing
tissue and muscle damage, chronic inflammation is widely attributed with
almost every disease known to the Western world. This includes heart
disease, cancer and a whole host of neurological disorders. Curcumin reduces
inflammation by lowering histamine levels and by
increasing the production of natural cortisone by the adrenal
glands. Extensive research over the past 30 years has shown that
curcumin plays an important role in the prevention and treatment
of various pro-inflammatory chronic diseases including
neurodegenerative, cardiovascular, pulmonary, metabolic,
autoimmune and malignant diseases. Oral administration of curcumin in instances of acute
inflammation was found to be as effective as cortisone or
phenylbutazone, and half as effective in cases of chronic
inflammation. Its anti-inflammatory properties may be attributed
to its ability to inhibit both biosyntheis of inflammatory
prostaglandins from arachidonic acid and neutrophil function
during inflammatory states. Oxidative stress has been implicated
in many chronic diseases, and its pathological processes are
closely related to those of inflammation, in that one can be
easily induced by another. In fact, it is known that
inflammatory cells liberate a number of reactive species at the
site of inflammation leading to oxidative stress, which
demonstrates the relationship between oxidative stress and
inflammation. In addition, a number of reactive oxygen/nitrogen
species can initiate an intracellular signaling cascade that
enhances pro-inflammatory gene expression. Inflammation has been
identified in the development of many chronic diseases and
conditions. These diseases include Alzheimer’s disease (AD),
Parkinson’s disease, multiple sclerosis, epilepsy, cerebral
injury, cardiovascular disease, metabolic syndrome, cancer,
allergy, asthma, bronchitis, colitis, arthritis, renal ischemia,
psoriasis, diabetes, obesity, depression, fatigue, and acquired
immune deficiency syndrome (AIDS). Clinical trials have also
shown that curcumin can reduce inflammatory mediators. The
regulatory effect of curcumin on immune cells is beneficial to
its treatment of inflammatory diseases. Curcumin mainly acts on
dendritic cells, T helper 17 cell, T regulatory cell. Curcumin
inhibits Th17 differentiation, and regulate Treg/Th17 rebalance
is by inhibit the IL‑23/Th17 pathway.29,30 Oxidative stress is
closely related to inflammatory processes. Curcumin reduces ROS
production due to its effect on nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase and increasing the
activity of antioxidant enzymes, and is related to Nrf2-Keap1
pathway. Curcumin reduces inflammation through its antioxidant
activity. Curcumin has significant anti-inflammatory effects,
and a large number of preclinical or clinical researches have
studied its effect on inflammatory diseases, among them,
inflammatory bowel disease, arthritis, psoriasis, depression,
atherosclerosis and COVID-19 are the focus of research hotspots.
Current evidences suggest that curcumin is effective in reducing
levels of inflammatory mediators, and that curcumin’s
anti-inflammatory properties may have a beneficial effect on
these diseases. Tumor necrosis factor α
(TNF-α) is a major mediator of inflammation in most diseases,
and this effect is regulated by the activation of a
transcription factor, nuclear factor (NF)-κB. Whereas TNF-α is
said to be the most potent NF-κB activator, the expression of
TNF-α is also regulated by NF-κB. In addition to TNF-α, NF-κB is
also activated by most inflammatory cytokines; gram-negative
bacteria; various disease-causing viruses; environmental
pollutants; chemical, physical, mechanical, and psychological
stress; high glucose; fatty acids; ultraviolet radiation;
cigarette smoke; and other disease-causing factors. Therefore,
agents that downregulate NF-κB and NF-κB–regulated gene products
have potential efficacy against several of these diseases.
Curcumin has been shown to block NF-κB activation increased by
several different inflammatory stimuli. Curcumin has also been
shown to suppress inflammation through many different mechanisms
beyond the scope of this review, thereby supporting its
mechanism of action as a potential anti-inflammatory agent. The high
concentrations of curcumin contained in turmeric act to target multiple
steps in the inflammatory pathway, blocking inflammatory markers at the
molecular level and thereby significantly lowering long-term inflammation in
your body.
Whether we are healing from an injury or an autoimmune disease, inflammation
is a common health challenge. Nutritionists, functional medicine GP’s and
physiotherapists commonly use curcumin for it’s anti-inflammatory qualities.
And it’s no wonder considering
six major scientific trials all found curcumin to possess a potent
anti-inflammatory action, which is completely non-toxic in nature. Recent findings suggest dietary
interventions, including curcumin supplementation, as a strategy
to combat inflammaging. Interestingly, the age-modulatory
properties and healthful effects of curcumin have been
illustrated in different cellular and animal models, including
C. elegans, Drosophila, and mice. As it was clearly discussed
above, curcumin was found to extend both healthspan and
lifespan, mainly blocking the most relevant proinflammatory
pathway NF-kB. In addition to the well-documented
evidence supporting the numerous biological properties of
curcumin in inhibiting NF-κB signaling dependent inflammation.
Indeed, curcumin was shown
to modulate the senescence-associated secretory phenotype
(SASP), which characterizes senescent cells and contributes to
fuel the inflammaging. Interestingly, the short-term
treatment of cells with low concentrations of curcumin decreased
the level of secreted pro-inflammatory cytokines such as IL-8 in
normal young cells. Moreover, lower doses of curcumin have
increased the production of sirtuin, i.e., NAD-dependent
deacetylases, and sirtuin 1 reduced inflammation by inhibiting
NF-κB signaling. Curcumin inhibits and regulates tissue
production and secretions of pro-inflammatory cytokine, such as
interleukin-4 (IL-4)
tumor necrosis factor alpha (TNF-α). Conversely, curcumin
can increase anti-inflammatory
cytokine production, such as IL-10 and soluble
intercellular adhesion molecule 1 (sCAM-1). In
preclinical studies, curcumin can reduce the degree of
inflammation of animal skin and prevent or reduce the
respiratory tract inflammation caused by viral or bacterial
infections. In clinical trials, the curcumin treatment improves
pain symptoms caused by
osteoarthritis and tissue inflammation and delays the
degradation of
articular cartilage, which improves the mobility and quality
of life in patient. Furthermore, curcumin also recovers the
effect of nicotine,
acetylcholine, serotonin,
barium chloride, and histamine on the reduction of
intestinal peristalsis. It
is
believed that curcumin exerts its effect in dose-dependent and
cell-context manner on the protein activity involved SASP.
Particularly, increasing evidence suggests that repeated
stimulation of innate immune responses over time results in the
development of inflammaging. In these settings, both an
increased burden of senescent cells during aging and a
hyper-stimulation of macrophages over time can play key roles of
inflammaging process. Recent reports of randomized controlled
trials conducted from 2008–2020 have demonstrated that curcumin
was able not only to modulate the antioxidant status but also
restore quantity, quality, and functional-metabolic status of
immune cells. This lends support to other data showing partial
anti-inflammatory, immunotropic and antioxidant activity of
turmeric extract in vitro and in vivo. Further implication of
curcumin in modulating aging-related inflammation through
lowering CRP level in dose-dependent manner in rats’ model was
reported. Moreover, MDA and NO levels were increased
significantly in animals fed with curcumin. This has
strengthened our belief that curcumin slows down the aging
process by suppressing age-related inflammatory indices. A
study
evaluating several pharmaceutical anti-inflammatories found that aspirin and
ibuprofen are the least potent, while
curcumin is among the most potent anti-inflammatory and
anti-proliferative agents available. Inflammation is
thought to be one of the major factors in all kinds of diseases, and
turmeric contains loads of curcumin, a powerful anti-inflammatory substance. It's been shown
to alleviate joint pain, and can even help with
heartburn and
indigestion. Researchers are also looking at curcumin for its
anti-aging properties.
Turmeric is safe and non-toxic and has been studied for
anti-inflammatory properties, inhibiting various molecules that
contribute to inflammation such as lipooxygenase, COX-2,
leukotrienes, prostaglandins, nitric oxide, interferon-inducible
protein, tumor necrosis factor (TNF), and interleukin-12
(IL-12). One study compared the effectiveness of Curcumin – the
active ingredient in turmeric – and a popular non-steroidal
anti-inflammatory drug (NSAID) called phenylbutazone. At the end
of the six days, those taking the Curcumin and the NSAID enjoyed
a significantly better anti-inflammatory response than placebo.
Curcumin in inflamed organs (liver, lung, brain and kidneys)
reduces the expression levels of NLRP3, IL‐1β, IL‐18 and
caspase‐1 and inhibits the inflammasome. Curcumin activated Nrf2
and inhibited NF‐kB. In the liver, curcumin directly targets
3'UTR‐rTXNIP with the help of miR200a and inhibits NLRP3
inflammasome. Curcumin reduces the severity of neurotoxicity by
inhibiting the formation of TXNIP/NLRP3 complex associated with
ER stress through the regulation of AMPK. Curcumin in
LPS‐stimulated mouse macrophages inhibits the activity of NLRP3
inflammasome by inhibiting potassium excretion, mitochondrial
instability, ASC oligomerization and speckle formation. In
addition to the above, ROS, autophagy, Sirtuin‐2 and acetylated
alpha‐tubulin are the targets used by curcumin in inhibiting the
inflammasome. In the lungs, curcumin effectively prevented the
increasing Notch1. In addition to inflammasome components,
curcumin effectively inhibits TLR4 and MyD88 expression and IBB
phosphorylation. Curcumin has a regulatory effect on several
molecules in the intracellular signal transduction pathways
involved in inflammation. |
According to Sandur et al. (2007), curcumin, demethoxycurcumin,
and bisdemethoxycurcumin are the active compounds in C.
longa that inhibit TNF-induced NF-κB activation.
Researchers discovered that curcumin has anti-inflammatory
properties by inhibiting the pro-inflammatory transcription
factor (NF-κB). Curcumin also inhibits the binding of activator
protein 1 (AP-1) binding factors, but the Sp1 binding factor
remained unaffected. Curcumin inhibits the activation of NF-κB
by phorbol ester and hydrogen peroxide, in addition to TNF-α.
Furthermore, curcumin suppresses the NF-κB activation pathway
after the convergence of multiple stimuli but before human I
kappa B alpha phosphorylation. Curcumin is equally
efficacious as cortisone or phenylbutazone when given orally in
acute inflammation. Curcumin’s therapeutic effect in sepsis
appears to be achieved by activation of peroxisome
proliferator-activated receptor gamma (PPAR-γ), which leads to
inhibition of pro-inflammatory cytokine along with expression
and release of TNF-α (Jacob et al., 2008). Majority of the
benefits seemed to be due to the anti-inflammatory and
antioxidant properties of curcumin, while the quercetin in the
molecule was negligible. Interestingly, anti-inflammatory effects of curcumin have been
shown to encompass the inhibition of MCP-1. Other
anti-inflammatory effects involved the downregulation of
inflammatory mediators such as COX-2 activity, lipoxygenase,
iNOS, MAPK, JAK and inhibition of TNF-α production, IL-1, -2,
-6, -8, and -12, macrophage migration inhibitory factor (MIF). A
recent study has shown that curcumin not only stimulated the
antioxidant system and reduced oxidative reactions in dogs but
also reduced leukocyte counts, which suggests mild
anti-inflammatory effects achieved in dogs fed with at a dose of
30 mg of curcumin/dog/day, These substantiate previous findings,
where it was observed that nursing lambs fed with curcumin had
lower total leukocytes, neutrophils, and lymphocytes. A similar
effect was reported in rats treated with 50 and 400 mg/kg
curcumin, indicating a remarkable improving effect on health and
the immune response. This points toward the importance of
curcumin in reversing the inflammatory responses and enhancing
the immune system performance, both playing a critical role in
ameliorating health and consequently slowing down aging (see
Figure 2).Curcumin has also been shown to
inhibit mediators of the inflammatory response, including cytokines,
chemokines, adhesion molecules, growth factors, and enzymes like
cyclooxygenase (COX), lipoxygenase (LOX), and inducible nitric oxide
synthase (iNOS). Nuclear factor-kappa B (NF-κB) is a transcription factor
that binds DNA and induces the transcription of the COX-2 gene, other
pro-inflammatory genes, and genes involved in cell proliferation, adhesion,
survival, and differentiation. The anti-inflammatory effects of curcumin
result from its ability to inhibit the NF-κB pathway, as well as other
pro-inflammatory pathways like the mitogen-activated protein kinase (MAPK)-
and the Janus kinase (JAK)/Signal transducer and activator of transcription
(STAT)-dependent signaling pathways. Inhibition of dextran sulfate sodium
(DSS)-induced colitis by curcumin in mice has been associated with a
downregulation of the expression of p38-MAPK and pro-inflammatory cytokine
TNF-α and a reduction of myeloperoxidase (MPO) activity, a marker of
neutrophil infiltration in intestinal mucosa. Curcumin has also been shown
to improve colitis by preventing STAT3 activation and STAT3-dependent
induction of cell proliferation in mouse colon. Moreover, curcumin was shown
to attenuate the immune response triggered by collagen injections in a mouse
model of rheumatoid arthritis, partly by blocking the proliferation of T
lymphocytes in mouse splenocytes. In addition, curcumin has been found to
reduce the secretion of TNF-α and IL-1β and the production of COX-2-induced
prostaglandin G2. In one study, curcumin inhibited the secretion of matrix
metalloproteins (MMPs) — responsible for the degradation of the synovial
joints — in human fibroblast-like synoviocytes and in human articular
chondrocytes. Curcumin has also been found to alleviate neuro-inflammation
in a mouse model of traumatic brain injury, reducing macrophage and
microglial activation and increasing neuronal survival. A placebo-controlled
trial in 40 men who had surgery to repair an inguinal hernia or hydrocele
found that oral curcumin supplementation (1.2 g/day) for five days was more
effective than placebo in reducing post-surgical edema, tenderness and pain,
and was comparable to phenylbutazone therapy (300 mg/day). Scientists now
believe that chronic, low-level inflammation plays a major role
in almost every chronic, Western disease. This includes heart
disease, cancer, metabolic syndrome, Alzheimer's and various
degenerative conditions. Therefore, anything that can help fight
chronic inflammation is of potential importance in preventing
and even treating these diseases. Curcumin is strongly
anti-inflammatory. In fact, it’s so powerful that it matches the
effectiveness of some anti-inflammatory drugs, without the side
effects. It blocks NF-kB, a molecule that travels into the
nuclei of your cells and turns on genes related to inflammation.
NF-kB is believed to play a major role in many chronic diseases.
The key takeaway is that curcumin is a bioactive substance that
fights inflammation at the molecular level. A 1999 study
published in the journal Phytotherapy Research found that the
primary polyphenol in turmeric, the saffron colored pigment
known as curcumin, compared favorably to steroids in the
management of chronic anterior uveitis, an inflammatory eye
disease. A 2008 study published in Critical Care Medicine found
that curcumin compared favorably to the corticosteroid drug
dexamethasone in the animal model as an alternative therapy for
protecting lung transplantation-associated injury by
down-regulating inflammatory genes. An earlier 2003 study
published in Cancer Letters found the same drug also compared
favorably to dexamethasone in a lung ischaemia-repurfusion
injury model. A 2004 study published in the journal Oncogene
found that curcumin (as well as resveratrol) were effective
alternatives to the drugs aspirin, ibuprofen, sulindac,
phenylbutazone, naproxen, indomethacin, diclofenac,
dexamethasone, celecoxib, and tamoxifen in exerting
anti-inflammatory and anti-proliferative activity against tumor
cells. Curcumin down‐regulates the expression of inflammatory
enzymes, such as COX2 and iNOS, inhibits the expression of the
5‐LOX pro‐inflammatory enzyme and chemokines and reduces the
expression of CRP and inflammatory cytokines of TNF‐α, IL‐6 and
IL‐8. Oral curcumin supplementation may potentially play a role in
inhibiting the COVID‐19 inflammation along with other drug
regimens by affecting these pathways and molecules and due to
applying anti‐inflammatory, antioxidant and anti‐apoptotic
properties without specific side effects. The spice worked as well as the
drug, but without the negative side effects.
Because of the crucial role of inflammation in most chronic diseases, the
potential of Curcumin
has been examined in neoplastic, neurological, cardiovascular, pulmonary and
metabolic diseases. The pharmacodynamics and pharmacokinetics of
Curcumin
have been examined in animals and in humans.
Clinically, chronic curcumin administration (375 mg, t.i.d., p.o., for
6–22 months) reduced the symptoms associated with idiopathic
inflammatory orbital pseudo-tumors in patients (Lal et al.
2000). In a study of curcumin’s anti-inflammatory
properties, Satoskar et al. evaluated the effects of this
polyphenol on spermatic cord edema and tenderness in 46 men
(15–68 years old) who had just undergone surgical repair of an
inguinal hernia and/or hydrocele. After surgery, patients were
randomly assigned to receive curcumin (400 mg), placebo (250 mg
lactose powder), or phenylbutazone (100 mg) three times a day
for 6 days. Curcumin proved to be superior by reducing all four measures of
inflammation. Curcumin binds to Toll-like receptors (TLRs) and
regulates downstream nuclear factor kappa-B (NF-κB),
Mitogen-activated protein kinases (MAPK), Activator Protein
1(AP-1) and other signaling pathways. Curcumin can down-regulate NF-κB through acting on Peroxisome
proliferator-activated receptor gamma (PPARγ). Curcumin can also
play anti-inflammatory effects by regulating The Janus
kinase/Signal transducer and activator of transcription
(JAK/STAT) inflammatory signaling pathway. Curcumin could
directly restrain the assembly of NLRP3 inflammasome, or
inhibits the activation of NLRP3 inflammasome by inhibition of
NF-κB pathway, which may be one of the mechanisms of curcumin
for the treatment of inflammatory diseases. In the studies
of inflammatory cells and animals, curcumin decreased levels of
pro-inflammatory mediators such as Interleukin-1, Tumor necrosis factor-α (TNF-α),
Inducible nitric oxide synthase (iNOS), NO, Regulated upon
activation normal T cell expressed and secreted factor(RANTES),
Granulocyte colony-stimulating factor (G‐CSF), and Monocyte
chemotactic protein‐1 (MCP-1). |
|
How may Curcumin work against CARDIOVASCULAR HEART Disease like
coronary atherosclerosis, hypertension, stroke, elevated ldl
cholesterol and triglyceride levels? |
Effect of Curcumin on Cholesterol and Triglyceride Levels
| Curcumin's
protective effects on the cardiovascular system include lowering
cholesterol and triglyceride levels, decreasing susceptibility
of low density lipoprotein (LDL) to lipid peroxidation, and
inhibiting platelet aggregation. In clinical researches,
curcumin is demonstrated to have the antihypertensive effects
while lowering blood pressure it can also increase myocardial
trophic blood flow. Curcumin increases VLDL cholesterol
trans-protein plasma, causing increased levels and
mobilization of α-tocopherol from adipose tissue that
protects against oxidative stress that occurs during
atherosclerosis. It was suggested that oral intake of 500 mg/day
curcumin for a week leads to a significant reduction in serum
lipid peroxide (33%) and total serum cholesterol (12%) levels
while increasing HDL cholesterol (29%). One study evaluated the effects of curcumin
in reducing the serum levels of cholesterol and lipid peroxides
in ten healthy human volunteers. Curcumin (at 0.5 g/day)
administered to the volunteers for 7 days reduced serum lipid
peroxides by 33% and total serum cholesterol levels by 11.63%,
and increased HDL cholesterol by 29%. Because of these
properties, curcumin was suggested to act as a chemopreventive
agent against atherosclerosis. Curcumin can reduce the viscosity of blood
and thrombosis formation via hindering the synthesis of
thromboxane A2 (TXA2) and regulating calcium signals to prevent
platelet activation and aggregation. Curcumin may affect
bleeding during menstruation and in repair of the endometrium,
because it can inhibit platelet aggregation. Therefore, it is
not proper to use during menstruation as it may cause excessive
menstrual blood volume and prolonged menstruation. In addition,
curcumin can inhibit the activation of NF-κB, AKT, and ERK to
protect and activate vascular endothelial cell from
incapacitation, which reduces arterial sclerosis, thrombosis,
and abnormal blood pressure. Clinical studies have shown that
curcumin reduces the recurrence rate in patients with coronary
artery obstruction disease and who have had installed vascular
stents within coronary artery. Turmeric extract demonstrated decreased susceptibility of LDL to
lipid peroxidation in addition to lower plasma cholesterol and
triglyceride levels. Higher doses decreased lipid peroxidation
of cholesterol and triglyceride levels. Curcumin's effect on
cholesterol levels may be due to decreased cholesterol uptake in
the intestines and increase conversion of cholesterol to bile
acids in the liver. Curcumin
may help reverse many steps in the heart disease process.
Perhaps the main benefit of curcumin when it comes to heart
disease is improving the function of the endothelium, which is
the lining of your blood vessels. It’s well known that
endothelial dysfunction is a major driver of heart disease and
involves an inability of your endothelium to regulate blood
pressure, blood clotting and various other factors. Several
studies suggest that curcumin leads to improvements in
endothelial function. One study found that it’s as effective as
exercise while another shows that it works as well as the drug
Atorvastatin. In addition, curcumin reduces
inflammation and oxidation (as discussed above), which play a
role in heart disease as well. One study randomly assigned 121
people, who were undergoing coronary artery bypass surgery,
either a placebo or 4 grams of curcumin per day, a few days
before and after the surgery. The curcumin group had a 65%
decreased risk of experiencing a heart attack in the hospital. A
study in
Nutrition Research in 2012, postmenopausal
women who took curcumin for eight weeks had an improvement in arterial
function, comparable to that seen in women who engaged in aerobic exercise.
Another
study in
Phytotherapy Research in 2013 found that
curcumin reduced triglycerides, while a
study in 2014 found that curcumin significantly reduced LDL
(“bad”) cholesterol and triglycerides in people with metabolic syndrome. Curcumin
also helps the endothelium (the lining of blood vessels) to function
at its optimum level, similar to the effect found during intense exercise.
Effect of Curcumin on Hypertension | Hypertension is a
condition in which the pressure on blood vessels is greater than
the normal pressure. A clinical study demonstrated that turmeric
(standardized to 22.1 mg of active curcumin) supplementation (3
capsules daily for three months) attenuated hematuria,
proteinuria and systolic blood pressure associated with
refractory or relapsing nephritis in patients without any
adverse events (Khajehdehi et al. 2012). In animal study,
curcumin administration downregulated the expression angiotensin
I receptor in vascular smooth muscle cells. In addition,
curcumin reduced angiotensin II-induced high blood pressure in
C57Bl/6J mice associated with downregulated expression of
angiotensin I receptor and decreased vasoconstriction in the
mesenteric artery (Yao et al. 2016). Further, curcumin
administration upregulated eNOS expression, decreased superoxide
enzyme level and downregulated p47phox NADPH oxidase expression
in vascular tissues, which is known to be responsible for
2kidney-1clip induced hypertension in rats (Boonla et al. 2014).
In another study, curcumin treatment increased the expression of
eNOS, decreased oxidative stress, restored glutathione redox
ratio in aortic tissues along with decrease in plasma protein
carbonyls, MDA and urinary nitrate/ nitrite levels in cadmium
intoxicated mice resulting in anti- hypertensive effect
(Kukongviriyapan et al. 2014). In conclusion, curcumin
supplementation effectively reduce hypertension via blocking
angiotensin I receptor, reducing circulating
angiotensin-converting enzyme, inducing vasodilation and
mediating nephroprotection. Stroke, sometimes called a “brain
attack”, occurs when blood circulation to a part of the brain is
blocked or ruptured. In animal studies, curcumin pre- and
post-treatment significantly improved CAT, glutathione
peroxidase (GPx) and SOD, while reduced TNF-a, IL-6, MDA and
xanthine dehydrogenase levels in forebrain tissue. In addition,
curcumin treatment significantly reduced apoptotic index induced
by bilateral common carotid artery occlusion/reperfusion in rats
(Altinay et al. 2017), increased the numbers of BrdU-positive
cells, BrdU/doublecortin-positive cells, activated notch
signaling pathway and stimulated neurogenesis during stroke (Liu
et al. 2016). Curcumin pretreatment (200 mg/kg, i.p., for 7
days) significantly decreased MDA, NO, TNF-a, IL-1b, caspase-3,
while increased SOD and GPx levels in the spinal cord of
ischemia-reperfusion injury in rats. Further, curcumin
administration reduced oxidative stress, inflammation and
apoptosis in spinal cord as well as reversed locomotor deficit
in rats (Gokce et al. 2016). Curcumin administration upregulated
eukaryotic initiation factor 4 A, adenosylhomocysteinase,
isocitrate dehydrogenase, ubiquitin carboxyterminal hydrolase
L1, while downregulated pyridoxal phosphate phosphatase
expressions in the cerebral cortex of rat (Shah et al. 2016a).
Curcumin treatment (50 mg/kg, i.p., for five days) downregulated
TNF-a, IL-6, Ac-p53 and Bax, while upregulated Bcl-2 and SIRT1
expression in brain. In addition, curcumin increased
mitochondrial cytochrome clevels, mitochondrial complex I
activity, mitochondrial membrane potential, while decreased
cytosolic cytochrome clevels in brain resulting in reversal of
mitochondrial dysfunction in transient middle cerebral artery
occlusion/reperfusion stroke model of rat (Miao et al. 2016).
Effect of Curcumin on Atherosclerosis |
Curcumin has an anti-atherosclerosis effect, possibly through
its anti-inflammatory properties.
Anti-hypercholesterolemic, anti-atherosclerotic (Gao et al.,
2019), and protective capabilities against cardiac ischemia and
reperfusion (Wang et al., 2018) of curcumin have been proven in
preclinical and clinical trials. Curcumin has anti-CVD potential
by improving the lipid profile of patients, and it might be
administered alone or as a dietary supplement to traditional CV
medicines (Qin et al., 2017). Curcumin is also seen in many
studies to protect against coronary heart disease (Li H. et al.,
2020) and also possesses anticoagulant properties. Curcumin limits the risk of
lipid peroxidation, which triggers inflammatory responses that
may lead to cardiovascular disease (CVD) and atherosclerosis,
due to its ability to scavenge reactive oxygen forms. Moreover,
curcumin and statins influence the same mediators of plasma
lipid changes. Experimental studies on atherosclerosis concluded
that the positive effects of curcumin on atherosclerosis were
associated with the dose of curcumin. Additionally, curcumin has
the ability to prevent endothelial dysfunction and smooth muscle
cell proliferation and migration. These properties
of curcumin are responsible for skewing macrophage polarization
from M1 to M2, regulating TLR4/MAPK/NF-κB pathways in
macrophages (which induce M2 polarization) and secreting
interleukins (IL-4 and/or IL-13). Moreover, curcumin may
indirectly maintain cell homeostasis by regulating the
expression and activity of lipid transporter, which is
responsible for cholesterol uptake and efflux. Zhou et al.
suggested that curcumin could be used as a therapeutic
supplement in atherosclerosis due to its ability to modulate
macrophage polarization through the inhibition of the toll-like
receptor (TL4)-mediated signaling pathway. This indicates that
curcumin is related to anti-inflammatory and atheroprotective
effects. Zhang et al. investigated the potential suppression of
atherosclerosis development by curcumin in ApoE-knockout mice by
inhibiting TLR4 expression in an animal model. Mice were fed a
high-fat diet supplemented with curcumin for 16 weeks and
compared to a control group (without curcumin supplementation).
The results indicated that, in vitro, curcumin at least
partially inhibited TLR4 expression, inhibited NF-κB activation
in macrophages, and, indeed, influenced the inflammatory
reaction. The causal role of curcumin in inhibiting TLR4
expression was also demonstrated by Meng et al. [46], who
indicated that its mechanism may be related to the blocking of
NADPH-mediated intra-cellular ROS production. Comprehensively,
the treatment of atherosclerosis and other cardiovascular
diseases with curcumin was shown to be effective in many
studies. Curcumin reduces the
activation of M1 macrophages. Curcumin regulates the polarization
and plasticity of macrophages by affecting TLR4/MAPK/NF-κB
pathway, which is beneficial to reduce atherosclerosis. In
ApoE−/− mice fed a high-fat diet supplemented with 0.1% curcumin
significantly decreased TLR4 expression in atherosclerotic
plaques and reduced the development of atherosclerosis. In
addition, curcumin supplementation can inhibit the activation of
NF-κB in aorta and the levels of IL-1β and TNF-α in aorta and
serum.122 Activation of the NF-κB pathway leads to activation of
NLRP3 inflammasome. Inhibition of NLRP3 inflammasome improves
atherosclerotic lesions in ApoE−/− rats,123 and
anti-inflammatory therapy targeting IL-1β reduces the recurrence
rate of cardiovascular events. Curcumin can inhibit
NF-κB-mediated NLRP3 expression, thereby inhibiting vascular
smooth muscle cell migration, and alleviating hypertension,
vascular inflammation and vascular remodeling in spontaneously
hypertensive rats, which is beneficial to cardiovascular
diseases including atherosclerosis.125 In ApoE−/− mice,
atorvastatin calcium and curcumin synergistically inhibited
adhesion molecules and plasma lipid levels, reducing foam cell
formation and inflammatory cytokines secretion by blocking
monocyte migration to the intima. Curcumin has significant
efficacy in the treatment of atherosclerosis in animal models.
Clinical evidence in non-atherosclerotic populations suggests
that curcumin can reduce lipid levels and inflammatory
responses, as it did in a mouse model. A meta-analysis of 20
randomized controlled trials with 1427 participants suggested a
significant decrease in plasma concentrations of triglycerides
and an elevation in plasma high-density lipoprotein cholesterol
(HDL-C) levels. In another randomized controlled
trial, administration of curcumin for 6 months increased the
level of adiponectin in serum, decreased pulse wave velocity and
reduced the level of leptin, uric acid, triglyceride, total body
fat, visceral fat and insulin resistance alongside lowered the
atherogenic risks in type 2 diabetic population (Chuengsamarn et
al. 2014). In animal study, curcumin administration reported to
possess anti-atherosclerotic activity by downregulating the
expression of lipocalin-2 in apolipoprotein E knockout mice (Wan
et al. 2016). Curcumin supplementation downregulated monocyte
chemotactic protein-1, P-selectin, vascular cell adhesion
molecule-1, intracellular adhesion molecule-1 and MMP (1, 2 and
9) expressions, exerting anti-atherosclerotic activity. It
oxidized LDL and lowered lipid levels in the serum of
hypercholesterolemic rabbits (Um et al. 2014). Another
mechanistic study revealed that curcumin supplementation
suppresses the expression of CD36 and aP2 in macrophages of
atherosclerotic mice (Hasan et al. 2014). In murine macrophage
line RAW264.7, curcumin reduced ox-LDL- induced TNF-a, IL-1b,
IL-6 production and apoptosis along with upregulation of
ATP-binding cassette transporter (ABCA1) and CD36 expressions,
thereby inducing lipid disposal and removal. Studies have shown
that endothelial dysfunction is a common cause of heart disease,
occurring when the endothelium is no longer able to regulate
blood pressure, clotting and a number of other factors.
Therefore, by improving endothelial function, curcumin lowers
your risk of heart disease. In addition to helping out the
endothelium, curcumin also reduces inflammation and oxidative
damage, two factors that are also common contributors to heart
disease. One study on 121 people—all of whom were undergoing
coronary artery bypass surgery—found that the group taking 4
grams of curcumin for a few days before and after the surgery
were much less likely to experience a heart attack. Other
studies have revealed that the anti-inflammatory action of
turmeric helps prevent artery disease. Valdez points out that
recent studies suggest curcumin can protect the heart from
ischemia—an inadequate blood supply to an organ or part of the
body, particularly the muscles within the heart. A study
published in the journal Drugs in R & D found that a
standardized preparation of curcuminoids from Turmeric compared
favorably to the drug atorvastatin (trade name Lipitor) on
endothelial dysfunction, the underlying pathology of the blood
vessels that drives atherosclerosis, in association with
reductions in inflammation and oxidative stress in type 2
diabetic patients. Curcumin capsules were found to enhance the
functioning of endothelium lining in the heart’s blood vessels.
Any abnormality in the endothelial functioning can cause blood
pressure or cause blood clotting. This dysregulation then leads
to heart disease. Recent research literature on Curcumin
supplement intake suggest its treatment potential on par with
the drug Atorvastatin or regular moderate exercise. Moreover,
the already proven benefits of Curcumin/Turmeric in terms of
their anti-inflammation and anti-oxidation properties has a
benign influence on the heart as well. Even coronary artery
bypass surgery patients were found to have a significant
decreased risk of suffering a relapse heart attack upon starting
a Curcumin capsule regimen. curcumin administration (4 g/day
beginning from 3 days before the surgery and continued up to 5
days after surgery) significantly attenuated myocardial
infarction associated with coronary artery bypass grafting via
antioxidant and anti-inflammatory effects (Wongcharoen et al.
2012). In animal study, curcumin sup- plementation (10, 20 or 30
mg/kg) significantly reduced oxidative stress, apoptosis and
infract size via stimulating janus kinase 2/signal transducer
and activator 3 of transcription (JAK2/STAT3) signaling pathway
thus protects myocardium in ischemia reperfusion rats (Liu et
al. 2017). In another study, curcumin administration (150 mg/kg)
downregulated the NF-jB expression, upregulated PPAR-cand Bcl-2
expression, thereby attenuated apoptosis and inflammation in
rats with myocardial infarction injury (Lv et al. 2016).
Curcumin is reported to protect hypoxia-induced cardiomyocytes
apoptosis via downregulation of specific protein 1 (SP1) and
upregulation of miR-7a/b expression in mice (Geng et al. 2016).
It is known to reduce fibrosis by activating cardiac
NAD-dependent deacetylase sirtuin (SIRT)-1 expression during
myocardial infarction in mice (Xiao et al. 2016). Curcumin
treatment inhibited the activity of MMPs, reduced MDA level,
restored extracellular matrix degradation and decreased
deposition of collagen in ischemic/ reperfused myocardium of
rats. In addition, curcumin supplementation downregulated
phospho-Smad2/3 and TGFb1 expression while upregulated mothers
against decapentaplegic homolog 7 expression in the infarcted
myocardium, which might prove to be effective for the management
of heart attack (Wang et al. 2012). In in vitro study, curcumin
attenuated apoptosis and induce autophagy by upregulating Bcl-2
and downregulating the expression levels of beclin-1, Bax, SIRT1
and Bcl2/adenovirus E1B 19 kDa protein-interacting protein 3
(BNIP3) in hypoxia reoxygenation-induced H9c2 myocytes (Huang et
al. 2015b). These findings revealed that curcumin reverses
myocardial infarction and heart attack via its antioxidant,
anti-inflammatory and anti-apoptotic properties.
|
|
How may
Curcumin work against kidney disease? |
Kidney disease is a
condition in which the kidneys lose the ability to balance
fluids and eliminate waste. In animal model, curcumin treatment
significantly reduced plasma MPO activity, thiobarbituric acid
reactive substances (TBARS) level, superoxide anion generation
while increased GSH levels in rat ischemia reperfusion model of
acute kidney injury. In addition, curcumin reduced plasma
potassium level, plasma uric acid level, microproteinuria and
blood urea nitrogen along with induced NMDA receptor antagonism
during acute kidney injury resulting in nephroprotective effect
(Kaur et al. 2016). Curcumin administration (200 mg/ kg, p.o.)
significantly reduced the level of MPO, IL-1b, IL-6, IL-10,
TNF-a, MDA and caspase-3 resulting in protective effect against
cisplatin induced renal dysfunction in male Wistar albino rats
(Topcu-Tarladacalisir, Sapmaz-Metin, and Karaca 2016). Curcumin
administration downregulated the expression of NAD(P)H oxidase
subunits (p22phox, p47phox and p67phox), cytochrome P450 2E1
(CYP2E1) and nitrotyrosine renal protein. In addition, curcumin
decreased inflammatory cytokine like IFNc, IL-1band TNF- a.
Besides, the expression of glucose regulated protein 78, MAPKs,
p-ERK1/2, p-JNK and C/EBP homologous protein (CHOP) were
downregulated. In the same study, curcumin administration
reduced apoptosis signaling proteins (cleaved caspase-12 and
cleaved caspase-3) in low-dose streptozotocin with high-fat diet
induced nonalcoholic steatohepatitis kidney disease in mice
(Afrin et al. 2017). Curcumin ameliorated kidney function via
reducing plasma adiponectin, plasma sclerostin, plasma cystatin
C while increasing renal CAT, SOD, Nrf2, GSH in adenine induced
chronic kidney Figure 4. Modulation of growth factor pathways
and intracellular signaling components by curcumin in its
anticancer effects. Curcumin treatment blocked the effect of
Shh-Gli1, Wnt/b-catenin, ATKs and AR pathways as well as its
downstream signaling components which lead to reduce cancer
incidence, cancer progression, treatment resistance and disease
relapse (Ali et al. 2018). Moreover, curcumin administration
reduced renal mesangial matrix expansion, reduced renal
hypertrophy, downregulated fibronectin and collagen IV
expressions, decreased the levels of NLRP3 protein, cleaved
caspase-1 and IL-1bin the renal cortices of db/db mice (Lu et
al. 2017). Curcumin treatment reduced fibrosis of kidney by
decreasing the methylation of CpG in the klotho promoter,
resulting in induction of klotho expression and inhibition of
TGF-bsignaling in cyclosporine A induced mouse model of kidney
disease (Hu et al. 2016). In earlier study, curcumin
administration reduced superoxide production,
nicotinamide-adenine dinucleotide phosphate oxidase 4 level,
carbonylation of protein, nitrotyrosine -protein level,
autophagy and mitochondrial fission while increased GSH/ GSSG
ratio which leads to reversal of nephrotoxicity induced by
maleate treatment in rats (Molina-Jij on et al. 2016).
Experimental data have conclusively proved that, curcumin
treatment reduces fibronectin and collagen IV expressions,
suppresses TGF-bsignaling and exhibits antioxidant,
anti-inflammatory and anti-apoptotic potential thereby
ameliorating kidney functions. |
|
How may
Curcumin work against skin disorders such as Psoriasis and
Dermatitis? |
Curcumin has
anti-inflammatory, anti-oxidative and immunomodulatory effects,
and can inhibit T cell activation, proliferation and production
of pro-inflammatory factors by acting on MAPKs, AP-1, NF-κB
pathways. In peripheral blood mononuclear cells of
psoriasis stimulated in vitro, curcumin can effectively inhibit
T cell proliferation, proinflammatory cytokines and
multifunction, and inhibit T cell production of IFN-γ, IL-17,
Granulocyte-macrophage colony stimulating factor (GM-CSF) and
IL-22. Curcumin down-regulation pro-inflammatory cytokines then
inhibits the proliferation of imiquimod-induced differentiated
HaCaT cells. Vascular endothelial growth factor transgenic mice
can be used as a model to study psoriasis. Because in the
transgenic rat model of keratin (K) 14-VEGF, the inflammatory
skin condition has psoriasis-like cellular and molecular
characteristics, including characteristic vascular changes and
epidermal changes. Cytokine levels of TNF-α, IFN-γ, IL-2, IL-12,
IL-22 and IL-23 were reduced to normal level after curcumin
treatment. This may be due to the curcumin inhibits currents of
Kv1.3 channel and thus inhibits proliferation of T cells, or
curcumin influence MAPKs, AP-1 and NF-κB signaling pathways in
the psoriasis mice. Furthermore, research shows that curcumin is
capable of relieving TPA-induced inflammation by directly
down-regulating IFN-γ production. In an imiquimod-induced
psoriasis model, curcumin could alleviate inflammation
symptoms; lower TNF-α, IL-17A, IL-17F, IL-22, and IL-1β mRNA
levels; and lower CC Chemokine receptor 6(CCR6) protein
expression. Curcumin has a variety of mechanisms for
psoriasis, curcumin can keep dendritic cells in immaturity, to
accelerate the anti-inflammatory macrophage phenotype
polarization, inhibiting proinflammatory factor and T cell,
restrain the vascular endothelial growth factor, effect on
psoriasis susceptibility genes, and so on, has great potential.
Curcumin is derived from natural plant ingredients, which has
good safety and can be used for a long time without causing
serious toxic and side effects. Considerable evidence, both in animals
and humans, indicates that curcumin may be effective against
psoriasis. One study investigated whether the anti-psoriatic
activity of curcumin in patients is due to suppression of PhK
activity. The authors of this study concluded that drug-induced
suppression of PhK activity is associated with resolution of
psoriatic activity and that the anti-psoriatic activity of
curcumin may be achieved through modulation of PhK activity was also found to reduce wound-healing time,
increase collagen growth and increase blood flow to the skin.
Curcumin effectively
reduced the level of phosphorylase kinase in the skin of
psoriatic subjects. In addition, the effectiveness of curcumin
to reduce phosphorylase kinase level was more pronounced than
calcipotriol (Thangapazham, Sharma, and Maheshwari 2007).
Clinically, oral curcumin administration (20 mg, p.o., b.i.d.)
reduced the level of serum IL-22 and alleviated psoriasis
vulgaris (Antiga et al. 2015). In animal study, curcumin
administration (40 mg/kg, for 20 day) exhibited significant
reduction in ear thickness, ear weight, ear redness and lymph
node weight in the keratin 14-VEGF transgenic mouse model of
psoriasis. Furthermore, curcumin treatment downregulated the
serum levels of IL-2, IL-12, IL-22, IL-23, IFN-cand TNF-ain
psoriatic mice. Curcumin administration inhibited Kv1.3 channel
and suppressed the cytokines expression and T cells
proliferation resulting in reduction of psoriasis phenotype
(Kang et al. 2016). Curcumin treatment decreased incrassation
and skin inflammation in mouse ear induced by imiquimod.
Curcumin application promoted epidermal TCR cd-cell
proliferation and downregulated C-C chemokine receptor type 6
expression in the ear skin of imiquimod-induced psoriasis (Sun,
Zhao, and Hu 2013). Curcumin reduces psoriasis-associated
inflammation as well as hyper- proliferation of keratinocyte
that suggest its role in development of antipsoriatic drug
(Aggarwal, Surh, and Shishodia 2007).
This study on curcumin and skin found it is highly beneficial
for scleroderma, psoriasis and skin cancer. Dermatitis,
also called as eczema, is a group of disease that describes the
inflammation of skin. The polyphenol curcumin has been
traditionally used by Asian countries to manage dermatitis
(Gupta, Kismali, and Aggarwal 2013a). In a randomized,
double-blind, placebo-controlled study, curcumin administration
(6g/day, p.o., t.i.d, during radiotherapy) was reported to
reduce the dermatitis severity in breast cancer patients (Ryan
et al. 2013). In animal model, curcumin treatment reduces the
inflammation of mouse epidermis by reducing the activity of
epidermal COX and lipoxygenase (LOX). The biological effect of
curcumin to reduce dermatitis is mainly due to inhibition of COX
and LOX activities. A phase II, open-label, Simon’s two-stage
clinical trial sought to determine the safety and efficacy of
oral curcumin in patients with moderate to severe psoriasis.
Twelve patients with chronic plaque psoriasis were enrolled in
the study and were given 4.5-g curcumin capsules every day for
12 weeks, followed by a 4-week observation period. Curcumin was
well-tolerated, and all participants completed the study.
Patients who responded to the treatment showed 83% to 88%
improvement at 12 weeks of treatment. |
|
How may
Curcumin work against Endocrine disorders such as Osteoporosis,
Hypothyroidism, and Hyperthyroidism? |
Curcumin administration
ameliorated microarchitecture of tibia bone through
down-regulation of MMP-9 expression, inhibition of
osteoprotegerin (OPG)/RANK ligand/RANK signaling and the
activation of microRNA-365 in dexamethasone treated mice (Li et
al. 2015a). It has been indicated that MiR-365 act as an
upstream regulator of MMP-9 during osteoporosis. Mechanistically
curcumin treatment ameliorated bone deteriorations through the
activation of miR-365 via suppressing MMP-9 (Li et al. 2015a).
One study revealed that, curcumin administration increased the
ratio of osteoprotegerin to receptor activator for NF-kB ligand,
ameliorated the proliferation of osteoblasts and activated the
Wnt signaling thereby alleviated osteoporotic symptoms induced
by glucocorticoid in rats (Chen et al. 2016). Curcumin treatment
(100 mg/kg for 2 month) increased bone mineral density,
downregulated the ratio of Bax/Bcl-2, downregulated cleaved
poly-ADP-ribose polymerase (PARP) and cleaved caspase-3,
upregulated p-ERK1/2 expression as well as reduced femoral
osteoblast apoptosis in glucocorticoid-induced osteoporosis rat
model (Chen et al. 2016). Recently, report suggests that
curcumin reversed hind-limb suspension-induced bone loss in rats
via upregulation of vitamin D receptor expression and
attenuation of oxidative stress (Xin et al. 2015). In in vitro
studies, curcumin treatment ameliorates the viability of
Saos-2 cells, reduces apoptosis, improves the mitochondrial
membrane functions and its potential, upregulates GSK3b and
protein kinase B (Akt) phosphorylation. These evidences of
curcumin administration supporting its potential for management
of osteoporosis (Dai et al. 2017). Curcumin reduce the risk of
osteoporosis via several mechanisms including reduction of
apoptosis, amelioration of mitochondrial membrane function, PKB
phosphorylation, microRNA-365 activation and osteoblasts
proliferation. upregulated expression of hepatic glutathione
reductase, GPx-1 and CAT were mitigated by concomitant
administration of curcumin and vitamin E in 6-propyl-thio-uracil
induced hypothyroid rats. In addition, curcumin and vitamin E
supplementation reduced the enhanced activity of MnSOD-2, GPx-1
and suppressed activity of glutathione reductase in
mitochondrial fraction. It was concluded that curcumin and
vitamin E supplementation modulate hepatic antioxidant gene
expression during hypothyroidism (Subudhi and Chainy 2012).
Curcumin administration significantly reduced the level of LPO
in cerebellum and cerebral cortex of
6-propyl-2-thiouracil-induced hypothyroidism in rats. In
addition, curcumin reversed the decreased level of translated
products SOD1 and SOD2 in rats with hypothyroidism (Jena et al.
2012). Interestingly, an earlier study suggested that, vitamin E
and curcumin administration restore the activity of serum
transaminase, altered rectal temperature and hepatic
histoarchitecture in rats with hypothyroidism induced by
6-n-propyl-2-thiouracil (Subudhi et al. 2009). Hyperthyroidism
In animal study, curcumin administration reduced lipid
peroxidation in the cerebral cortex of l-thyroxine induced
hyperthyroid rats. Interestingly, curcumin reduced the activity
of SOD, SOD1 and SOD2 in cerebral cortex, while enhanced the SOD
and SOD1 activity in the cerebellum of hyperthyroid rat (Jena,
Dandapat, and Chainy 2013). In another study, curcumin and
vitamin E administration reversed the reduced levels of hepatic
SOD and CAT. Besides, curcumin administration upregulated the
expression of glutathione peroxidase-1 and glutathione reductase
in rat liver. In the same study, co-treatment of curcumin along
with vitamin E alleviated oxidative stress and liver damage in
l-thyroxine induced hyperthyroid rats (Subudhi and Chainy 2010).
Further, l-thyroxine induced hyperthyroidism and its associated
increase in activity of ALT and AST in rat serum were reduced by
curcumin and vitamin E treatment resulting in hepatoprotection
(Subudhi et al. 2008). These finding suggest that, curcumin
administration exerts neuromodulatory and hepatoprotective
activity during hyperthyroidism mainly due to its antioxidant
effect. |
|
How may
Curcumin work against Respiratory disorders such as asthma,
pulmonary disease, Pneumonia, and allergies? |
Curcumin inhibited the degranulation
and release of histamine from rat peritoneal mast cells caused
by compound 48/80. In an animal model, curcumin dramatically
reduced the mast cell-mediated passive cutaneous anaphylactoid
reaction. Curcumin enhanced intracellular cAMP levels and
inhibited both nonspecific and selective mast cell-mediated
allergy reactions (Choi et al., 2010). Curcumin significantly
reduced IgE/Ag-induced PSA (passive systemic anaphylaxis), as
measured by serum-dependent leukotriene C4, dependent
prostaglandin D2, and histamine levels, indicating that it might
be useful to produce drugs for allergic inflammatory illnesses
(Li et al., 2014). Curcumin can suppress expression of CD80,
CD86, and class II antigens by dendritic cells and blocks the
release of inflammatory cytokines like IL1β, IL-6, and TNF-α
from LPS-stimulated dendritic cells. Chronic obstructive
pulmonary disease (COPD) is a progressive airflow limitation
disease associated with persistent inflammation of respiratory
system, especially in the airways and lungs. COPD is caused by
long-term exposure with noxious particles, gases, such as air
pollutants or smoke. The preclinical studies in animal model,
there are anti-inflammatory effects of curcumin can reduce and
alleviate respiratory inflammation and oxidative stress caused
by exposure to soot or other air pollutants. Curcumin also
reduces allergic asthma by inhibiting the PPARγ/NF-κB signaling
pathway in respiratory mucosa to prevent COPD. When lower
airways and lung parenchyma with severe acute lung injury or
inflammation by drugs or infection may cause plasma
extravasation, which leads to lung infiltration filled with
interstitial fluid and leukocytes. During the recovery from
severe lung infiltration, some patients will develop fibrous
tissue hyperplasia and pulmonary fibrosis, resulting in a
significant reduction in lung gas exchange area and efficiency.
For example, clinical application of chemotherapeutic drugs or
radiotherapy can cause acute lung injury and lead to pulmonary
fibrosis and curcumin treatment can attenuate the severity of
pulmonary fibrosis. There are several inflammatory cytokines
related with pulmonary fibrosis, include TNF-α, TNF-β1, IL-6,
and IL-4, ROS, MMPs, and TGF-β, and treated with curcumin can
inhibit those cytokine expressions. Today's most famous
coronavirus, patients with SARS virus and COVID-19 infection
will often have sequelae of severe pulmonary fibrosis after
healing from viral infection, and curcumin also can act on the
spike protein to interrupt the covid-19 infection. Many clinical
studies on pulmonary fibrosis have pointed out that curcumin or
turmeric can significantly reduce the expression of
inflammation-related factors in cells and tissues, effectively
moderates excessive inflammation in the acute phase of lung
injury or infection, and prevents pulmonary fibrosis in the
later stage. Asthma is a chronic lung
disease involving the inflamed, swell and narrowed airways that
produce extra mucus, which causes breathing difficulties.
Clinically, curcumin administration (500 mg/day for 30 days)
ameliorated the mean forced expiratory volume one second values
resulting in alleviation of airway obstruction alongside
improved haematological parameters in asthmatics (Kunnumakkara
et al. 2017). In animal study, intranasal curcumin
administration attenuated the pulmonary fibrosis and
inflammation of airway by downregulation of MMP-9, eotaxin,
TIMP-1 and a-smooth muscle actin expressions in the lung tissue
of ovalbumin-induced chronically asthmatic mice (Chauhan,
Dash, and
Singh 2017). In another study, curcumin administration reduced
inflammatory markers like IL-4 and INF-c levels in lung tissue
alongside reduced asthma symptoms by activation of Wnt/b-catenin
signaling pathway in ovalbumin challenged mice (Yang et al.
2017c). Further, curcumin administration suppressed the
activation of JNK54/ 56, ERK 42/44 and p38 MAPK resulting in
inhibition of COX-2 expression and prostaglandin (PG) D2
release, which is known to reduce airway obstruction,
inflammation and asthma progression in ovalbumin challenged
mouse model of asthma (Chauhan et al. 2016). Evidence suggested
that lipopolysaccharide exposure causes increase in level of
IgE, IL-4, IL-5, histamine and MPO resulting in exacerbation of
airway inflammation in rats and these effects were efficiently
reversed by curcumin administration (Kumari, Dash, and Singh
2015). Curcumin treatment is reported to attenuate the
production of IgE, accumulation of inflammatory cells and
hyperplasia of goblet cell alongside ameliorated the secretion
of mucus and hyper-responsiveness of airway in asthmatic mice. In
addition, curcumin administration increased the activity of HO-1
and Nrf-2 while reduced p-IjB and NF-jB levels in the lung
tissue of ovalbumin challenged female specific pathogen-free
BALB/c mice (Liu et al. 2015). Their mechanism of action is
associated essentially due to its anti-oxidative and
anti-inflammatory activities in asthma. At molecular and
cellular levels, curcumin treatment reduces asthma symptoms
mainly due to inhibition of histamine release, attenuation of
IgE, inhibition of COX-2 enzyme and suppression of JNK54/56, ERK
42/44 and p38 MAPK activation (Chauhan et al. 2016;He et al.
2015c). Chronic obstructive pulmonary disease (COPD) is a
progressive inflammatory lung disease that causes obstruction in
airflow and difficulty in breathing. In animal study, curcumin
administration is known to ameliorate right ventricular
hypertrophy index and right ventricular systolic pressure via
activation of suppressor of cytokine signaling (SOCS) 3/
JAK2/STAT signal transduction in lung tissue of rat with chronic
obstructive pulmonary disease (Lin, Chen, and Liu 2016).
Curcumin treatment downregulated macrophage inflammatory protein
(MIP)-2a, IL-8 and MCP-1 expressions while upregulated histone
deacetylase 2 expression, ameliorated methylation of H3K9 and
reduced H3/H4 acetylation in type II alveolar epithelial cells
during cigarette smoke exposure induced chronic obstructive
pulmonary disease in rats (Gan et al. 2016). Further, it was
reported that, curcumin administration reduce TNF-a, IL-6, IL-8
level, macrophages count, neutrophil numbers and total cell
numbers alongside reversed ultrastructural damage and emphysema in bronchoalveolar lavage fluid of cigarette smoke exposure
combined intratracheally administered lipopolysaccharide induced
chronic obstructive pulmonary disease in rats. Additionally,
curcumin downregulated alveolar epithelia p66Shc and p-p66Shc
expression, which is associated with protection of alveolar
epithelial injury (Zhang et al. 2016c). We conclude that
curcumin suppresses the progression of chronic obstructive
pulmonary disease by inhibiting the inflammation of airways.
These findings suggest that curcumin could be used to protect
chronic obstructive pulmonary disease in human and animals.
Pneumonia is an inflammatory condition caused by
bacteria, viruses or fungi in one or both lungs. In animal
model, curcumin treatment reduced pneumonia in female C57BL/6J
mice caused by Staphylococcus aureus via inhibiting the
pore-forming activity of a-hemolysin, an extracellular protein
secreted by bacteria that is known to induce the lung infection
(Wang et al. 2016a). Further, curcumin significantly reduced S.
aureus-mediated lung edema, barrier disruption, vascular leakage
and pneumonia. In addition, curcumin administration
significantly reduced neutrophils infiltration and attenuates
plasminogen activator inhibitor-1 activation, resulting in
reduction of chemokines and cytokines in staphylococcus
aureus-infected mouse model of pneumonia (Xu et al. 2015). Thus,
continued studies of the potent anti-inflammatory,
anti-microbial, anti-oxidant agent, curcumin, will likely use to
reverse or slow the progression of pneumonia, ultimately,
leading to novel treatments for pulmonary dysfunction in
critically ill patients (Avasarala et al. 2013). Allergies, also
known as allergic diseases, are a number of conditions in which
the immune system reacts abnormally to a foreign substance. In a
randomized, double-blind study, chronic curcumin administration
(500 mg/day, p.o., for consecutive 2 months) significantly
alleviated rhinorrhoea, sneezing and nasal congestion in
patients by reducing nasal airflow resistance. In addition,
curcumin administration suppressed TNF-a, IL-4 and IL-8, while
increased the production of soluble intercellular adhesion
molecule and IL-10 (Wu and Xiao 2016). Curcumin administration
(2.5 or 5 mg/kg, for four days) suppressed the level of IgE in
the serum of asthmatic mice. Further, it reduced the level of
secretory phospholipase A2, COX-2, nitric oxide, IL-4 and IL-6
in bronchoalveolar lavage fluid. In addition, curcumin
administration downregulated the expression of p38, COX-2, p-ERK
and p-JNK in the lungs tissue of ovalbumin challenged mice
(Chauhan et al. 2016). Study revealed that curcumin treatment
significantly reduce histamine release and downregulate TNF-a,
IL-1b, IL-6, IL- 8, p-ERK, p-p38, p-JNK, p-IkBaand NF-kB p65
expressions in mast cells. Besides it decreased the levels of
IgE, histamine, TNF-a, Src kinases, Fyn, Lyn and Syk in the
serum of mice with allergic rhinitis induced by ovalbumin (Zhang
et al. 2015b). Curcumin supplementation significantly attenuated
lipopolysaccharide induced allergic asthma by reducing airway
inflammation and decreasing IgE level, histamine release and
oxidative stress in mice (Kumari, Dash, and Singh 2015).
Further, curcumin administration inhibited intestinal
mastocytosis, expression of Th2 cytokines, intestinal
anaphylaxis and activation of NF-jB in ovalbumin. These findings
suggest that, the anti-allergic mechanism of curcumin is
essentially due to its anti-inflammatory and anti-oxidative
activities. At cellular and molecular levels, curcumin treatment
reduces allergic symptoms mainly due to attenuation of IgE,
inhibition of histamine release, inhibition of COX-2 enzyme,
stimulation of Nrf- 2/ HO-1 pathway etc. (Chong et al. 2014;
Kurup and Barrios 2008; Lee et al. 2008). |
|
What are the scientific properties of Curcumin? |
Chemical Name |
Diferuloylmethane |
Definition |
A β-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups |
Systemic Name |
(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) |
Empirical Formula |
C21H20O6 |
Linear Formula |
[HOC6H3(OCH3)CH=CHCO]2CH2 |
Molecular
Weight |
368.38 g/mol |
Appearance |
Bright yellow-orange powder |
Melting Point |
183 °C, 361 °F |
PubChem |
969516 |
Biofunction |
Enzyme cofactor |
Chemical Taxonomy |
Organic Chemicals / Hydrocarbons / Aromatic
Compounds / Phenols / Catechols / Curcuminoids |
Chemical Structure |
|
Taxonomic hierarchy |
Kingdom Subkingdom Superdivision Division Class Subclass Order Family Genus Species |
Plantae
(Plants) Tracheobionta (Vascular plants) Spermatophyta (Seed plants)
Magnoliophyta (Flowering plants) Liliopsida (Monocotyledons)
Zingiberidae Zingiberales Zingiberaceae (Ginger family)
Curcuma (Curcuma) Curcuma longa (Turmeric) |
|
Why may curcumin extracted
from Turmeric root provide health benefits?
|
Natural plant products
have been used throughout human history for various purposes.
Having co-evolved with animal life, many of the plants from
which these natural products are derived are billions of years
old. Natural polyphenol compounds derived from plants, such
as curcumin, have many favorable biological properties. Certain plants manufacture chemicals that repel
predators, herbivores, parasites and diseases. These chemicals
are produced as secondary metabolites by higher plants as a
natural defense mechanism against disease and infection. Many of
these natural chemicals have pharmacological or biological
activity, and these medicinal plants have played a pivotal role
in the health care of many cultures, both ancient and modern.
Medicinal plants and their bioactive ingredients, in particular
polyphenols, have been implicated in various biological
activities, including, but not limited to, immunomodulation,
anti-inflammatory, cardiovascular protection, antioxidant, and
anticancer potential. Like most of these pharmacologically-active metabolites,
curcumin is involved in self-defense. Over time, plants with higher levels of
organic compounds that deter attackers become more successful, because of their
advanced protection. In nature's never-ending interaction between predator and prey,
insects evolve the ability to digest plant toxins, while plants evolve stronger chemicals to deter their enemies. Monitoring
this evolution between plants and insects represents an important field of
ecological research. Scientists have discovered that many phytochemicals manufactured
in plants and roots not only prevent insect attack or fight plant infections, but also provide
human health benefits.
Many cultures create their own botanical pharmacies as
the lore of medicinal plants and remedies is handed down through generations of
healers. Medicinal plants have been used as a traditional treatment agent for
numerous human diseases since ages in many parts of the world.
In rural areas of the developing countries, they continue to be
used as the primary source of medicine. With the advent
of sophisticated laboratory testing, biologists are finding that the many
indigenous plants and roots from around the world provide medicinal
value, and their metabolites are candidates for research. Pharmaceuticals, nutraceuticals, phytotherapeutics and herbal medicines are found thanks to
ethnobotany and developed by researching and analyzing
compounds derived from plants. These include aspirin, which
contains salicylic acid derived from willow bark, morphine
derived from Papaveraceae somniferum (opium poppy), and
chemotherapeutic drugs including paclitaxel (taxol) derived from
Taxus brevifolia (Pacific Yew), vinblastine and vincristine
derived from the Madagascar periwinkle plant (Catharanthus
roseus), taxotere (docetaxel) derived from the European yew
(Taxus baccata), fungal metabolite etoposide derived from
the roots of mayapple plants (Podophyllum peltatam), tenioposide
derived from the wild mandrake (Podophyllum peltatum), and many
others like resveratrol from grapes, pterostilbene from
blueberries, and catechins from green tea which contain
polyphenolic antioxidants and have been studied for medicinal
and
preventive value. Turmeric derived from the Curcuma longa plant
contains the polyphenols curcumin, demethoxycurcumin, and
bisdemethoxycurcumin, and it has caught the attention of
researchers due to its extensive use as a culinary ingredient
(the bright yellow color of curry is attributed to turmeric) in
most Asian countries and the many reports of its antioxidant,
antimicrobial, and anti-inflammatory properties. Curcumin
(diferulolylmethane) is extensively utilized in a variety of
settings including cosmetic and herbal supplementation, and its
medicinal properties have been investigated for more than 50
years. Curcumin’s structure is similar to other natural
polyphenolics (chemicals containing multiple "phenol" groups)
produced by plants in response to infectious attack. These
natural polyphenols often have potent antioxidant and
anti-inflammatory properties as well as immune support health
benefits. Every medicinal molecule in all of
botany is made out of carbon dioxide. CO2 is the key source of carbon used by
plants to synthesize everything from curcumin to resveratrol. Every healing
nutrient in basil, oregano, cinnamon, turmeric, garlic and pomegranate fruit is
made out of carbon dioxide. Curcumin, a powerful anti-cancer nutrient found in
turmeric, is made from carbon dioxide, with 21 carbon molecules manufactured
from atmospheric carbon dioxide. Curcumin has been
studied for antioxidant, anti-inflammatory,
antiviral, antibacterial, antifungal, and anticancer activities, mediated
through the regulation of various transcription factors, growth factors,
inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits
activities similar to recently discovered TNF blockers (humira, remicade and
enbrel), vascular endothelial cell growth factor blocker (avastin), human
epidermal growth factor receptor blockers (erbitux, erlotinib, and geftinib),
and HER2 blocker (herceptin). With
antioxidant, anti-inflammatory and antitumor properties,
curcumin has received much attention in several
neurodegenerative diseases, such as Alzheimer’s (AD), Huntington
(HD) and Parkinson’s diseases (PD). Extensive research over
several decades has sought to identify the mechanisms of
molecular action of curcumin. It regulates inflammatory
cytokines, growth factors, growth factor receptors, enzymes,
adhesion molecules, proteins related to apoptosis and cell-cycle
proteins, such as cyclin, and modulates its molecular targets by
altering their gene expression, signaling pathways or through
direct interaction.
Considering the recent scientific bandwagon that
multi-targeted therapy is better than mono-targeted therapy for most diseases,
curcumin is a phytonutrient that can be considered an ideal "Spice for Life". More than 5000
papers published within the past two decades have revealed that curcumin has
extraordinary potential in promoting health through modulation of numerous molecular
targets. The importance of curcumin can be estimated by the fact that
thirty-seven cases of clinical trials of curcumin were
completed by December 2017 and FDA (Food and Drug
administration) clinical phase 4 trials have been completed. |
|
Why hasn't
the pharmaceutical industry patented Curcumin? |
Pharmaceutical
corporations tried registering patents for curcumin and
turmeric because of the much heralded scientific
evidence and the long history of its healing properties.
However, that same
evidence and history of
curcumin being used medicinally for centuries was the reason the United
States Patent and Trademark Office rejected and revoked the rights
for turmeric patent 5401504
on the grounds that the claims were
not new: "USPTO
unequivocally rejected all six claims made on August 13, 2001 while ruling that Turmeric's
medicinal properties were not patentable." University of Texas MD
Anderson Cancer Center states
"in
the case of curcumin, a natural compound, no company can reap the benefits if
turmeric shows itself to be an effective anti-cancer drug."
And because curcumin is not economically interesting,
"it is almost impossible to get financial support to conduct a
clinical trial with a substance that cannot be patented. The
greatest challenge will be to find sponsors for clinical
research on curcumin, as this promising plant-derived compound
cannot be exploited economically." |
|
What is the history of Curcumin and Turmeric?
|
Turmeric | The name turmeric
derives from the Latin word terra merita (meritorious
earth), referring to the color of ground turmeric which
resembles a mineral pigment. The Arabic word for turmeric is
kurkum, which originally meant ‘saffron.’ The word kurkum
in Hebrew is karkom as it is written in the Bible. Medieval Arabic
literature called turmeric zaʿfarān hindī
which means "Indian saffron". According to Sanskrit
medical treatises and Ayurvedic and Unani systems, turmeric has
a long history of medicinal use dating back to the Vedic period (ca.
1500–ca. 500 BC). It is featured in the Suśrutasaṃhitā, the
foundational text of traditional Indian medicine, as an
ingredient to alleviate the effects of poisoned
food (Prasad, 2011). Curcuma Longa originated in India
and has a history of 6000 years. The recorded use of turmeric
dates back nearly 4000 years to the Vedic culture in India,
where it was used as a culinary spice and had some religious
significance. The use of turmeric is most salient in the various
island cultures of the Pacific, where it spread with the
Austronesian expansion there starting around 3000 BC, reaching
as far as Polynesia and Fiji, and was used as a dye and
ceremonial substance (McClatchey, 1993; Prance & Nesbitt, 2005;
Sopher, 1964). Susruta’s
Ayurvedic Compendium, dating back to 250 BC, recommends an
ointment containing turmeric to relieve the effects of poisoned
food. Researchers in India recently identified mineral remnants
of turmeric on the cooking pots of ancient Indus River remains,
one of the first urban civilizations. These ancient
civilizations have vast trial and error experience with many
different herbal remedies and food preparations and they
selected curcumin for medicinal use based on efficacy. According
to Nair (2019, p. 2), its maritime dispersion from India
intensified in the Middle Ages, reaching the coast of China in
the seventh century AD, East Africa a century later, West Africa
by 1200, and Jamaica in the eighteenth century. In Chinese
medicinal literature, turmeric first appears in the Xinxiu
Bencao, and the Bencao Gangmu treats it as well (Feng
et al., 2011). From its initial diffusion up to Vasco da Gama’s
journey and landing in Kozhikode, it was Arab traders who were
instrumental in the westward spread of turmeric, similarly to
pepper and other spices of the time. In 1280, Marco Polo
described turmeric in the China leg of his travels; "There is
also a vegetable which has all the properties of the true
saffron, as well the smell as the colour, and yet it is not
reall saffron. It is held in great estimation, and being an
ingredient in all their dishes, it bears, on that account, a
high price." -
The Travels of Marco Polo, the Venetian Curcumin | Curcumin
is a vibrant yellow compound found in turmeric root and was first isolated in 1815 by two German
scientists, Vogel and Pelletier. They reported on the “yellow
coloring-material” from the rhizomes of the East Indian plant
Curcuma longa and named it curcumin. In 1842,
they identified curcumin as the most abundant molecule and the
primary curcuminoid in turmeric, which they isolated into pure curcumin.
It was not until 1910 that the chemical structure of curcumin
was established as diferuloylmethane by
Miłobȩdzka, Kostanecki, and Lampe in 1910,
who determined it was
1,6-heptadiene-3,5-dione-1,7-bis(4-hydroxy-3-methoxyphenyl)-(1E,
6E) and could be synthesized chemically. An early mention of curcumin in
modern medical literature was its first clinical trial,
appearing in the Lancet in 1937, one of the most prestigious
medical journals. The article, describing curcumin applications
to humans, was written by Albert Oppenheimer—then an assistant
professor at the American University of Beirut, Lebanon, who
applied curcumin orally for the treatment
of 67 patients suffering from various forms of subacute,
recurrent, or chronic cholecystitis. The positive therapeutic
response recorded then, was the basis for future interest in
curcumin and its healing properties, especially its
anti-inflammatory properties, which were among the first
studied. The first study on its biological activity as an
antibacterial agent was published in 1949 in Nature. Curcumin's
biological properties were described as responsible for most of
the therapeutic efficacy of turmeric in the 1970s when the first
research on curcumin’s health benefits was carried out. In these
and in later studies it was shown that curcumin has multiple
therapeutic potentialities (Di Mario et al., 2007; Adhvaryu et
al., 2008; Chandran and Goel, 2012; Yanpanitch et al., 2015;
Gera et al., 2017; Salehi et al., 2019a). Although
the current database indicates over 12,000 publications on
curcumin, until 1990 there were less than 100 papers published
on this nutraceutical.
In 2007,
Payton et al showed that curcumin's form exists in
solution as a keto−enol tautomer. Numerous
studies have indicated that curcumin is a highly potent
antimicrobial agent and has been shown to be active against
various chronic diseases including various types of cancers,
diabetes, obesity, cardiovascular, pulmonary, neurological and
autoimmune diseases. Furthermore, this compound has also been
shown to be synergistic with other nutraceuticals such as
resveratrol, piperine, catechins, quercetin and genistein.
Curcumin's
molecular identity is characterized by unique polyphenolic
elements, specifically two feruloyl groups linked via a
methylene chain. This molecular configuration plays a crucial
role in its biological and chemical properties. For generations,
curcumin has been a key component in the traditional medicinal
practices of various Asian cultures. Its use in Ayurvedic and
traditional Chinese medicine, along with other herbal systems,
has been extensive. Curcumin has been applied to treat a wide
range of ailments, from inflammation and pain to more specific
conditions such as jaundice, menstrual issues, bleeding, dental
pain, bruises, and cardiac pain. In the realm of
contemporary science, curcumin has sparked considerable interest
due to its potential health benefits. Studies have delved into
its effectiveness against chronic illnesses like cancer,
Alzheimer’s disease, heart diseases, and inflammatory conditions. This interest is fueled by its properties as an
antioxidant and an anti-inflammatory, and its possible role in
cancer prevention. Scientists are examining how curcumin
influences various cellular processes by interacting with
multiple signaling molecules, including growth factors,
cytokines, and the genes involved in cell life cycle and
division. The high degree of reverence
is established by
the fact that it is used in so many cultures:
Arabic
Kurkum, Uqdah safra. Armenian
Toormerik, Turmerig. Assamese
Halodhi. Bengali
Halud. Bulgarian
Kurkuma. Burmese
Hsanwen, Sanwin, Sanae, Nanwin.
Catalan
Cúrcuma. Chinese
yujin [yü-gold]Yu chin, Yu jin, Wohng geung, Geung wohng, Wat gam, Huang jiang,
薑黃
Jiang huang, Yu jin xiang gen.
Croatian
Indijski šafran, Kurkuma.
Czech Kurkuma, Indický Šafrán,
Žlutý kořen, Žlutý zázvor.
Dhivehi Reen’dhoo.
Danish
Gurkemeje. Dutch
Geelwortel, Kurkuma Tarmeriek, Koenjit, Koenir.
English
Turmeric, Curcumin, Indian saffron.
Estonian
Harilik kurkuma, Kurkum, Pikk kollajuur, Lŏhnav kollajuur,
Harilik kurkuma, Kurkum, Pikk kollajuur, Lŏhnav kollajuur.
Farsi
Zardchubeh. Finnish
Kurkuma, Keltajuuri. French
Curcuma, Safran des Indes, Terre-mérite, Souchet des Indes.
Galician
Cúrcuma. German
Curcuma, Sárga gyömbérgyökér.
Greek Kitrinoriza, Kourkoumi,
Kourkoumas Gujarati Halad, Haldar.
Hebrew
Kurkum, Kurkume. Hindi
Haldi. Hungarian
Kurkuma, Sárga gyömbérgyökér.
Icelandic Túrmerik.
Indonesian
Kunyit, Kunir, Daun kunyit.
Italian Curcuma.
Japanese
Ukon, Tamerikku Kannada Arishina, Arisina.
Khmer
Romiet, Lomiet, Lamiet. Korean
Kang-hwang, Keolkuma Kolkuma, Sim-hwang, Teomerik, Tomerik,
Tumerik, Ulgum, Ulgumun.
Laotian Khi min khun, Khmin
khÜn. Latvian
Kurkuma. Lithuanian
Ciberžole, Kurkuma, Dažine ciberžolé.
Malay
Kunyit basah. Malayalam
Manjal Marathi Halad. Nepali
Haldi, Hardi, Besar. Norwegian
Gurkemeie Pahlavi Zard-choobag.
Pashto
Zarchoba. Polish
Kurkuma, Ostryź długi, Szafran indyjski.
Portuguese
Açafrão da Índia, Curcuma.
Punjabi Haldi.
Romanian
Curcumǎ. Russian
Koren, kurkumy, Kurkuma.
Sanskrit haldi.
Singhalese
Kaha. Slovak
Kurkuma. Slovenian
Kurkuma. Spanish
Cúrcuma, Azafrán arabe.
Swahili Manjano.
Swedish
Gurkmeja. Tagalog
Dilaw. Tamil
Manjal. Telugu
Haridra, Pasupu. Thai
Kha min chan, Kha min; Wanchakmadluk.
Tibetan
Gaser, Sga ser. Turkish
Hint safrani, Sari boya, Zerdeçal, Safran kökü, Zerdali,
Zerdeçöp, Zerdecube. Ukrainian
Kurkuma. Urdu
Haldi, Zard chub. Vietnamese
Bot nghe, Cu nghe, Nghe, Uat kim, Khuong hoang. |
|
|
What is Turmeric-Curcumin.com?
|
Turmeric-Curcumin.com
is our company and website, dedicated for over twenty four
years to researching, manufacturing and distributing the highest
quality curcumin 95% extract. Since our establishment in 2000,
we've been dedicated to offering the best customer service without the
typical marketing hype, allowing us to maintain the lowest
prices in the industry. Unlike merchants with numerous products and categories,
we've remained focused on
wholesaling and retailing the
single most beneficial compound in botanical
medicine; curcumin, standardized and
purified to 95% extract. This extraordinary herbal extract of
turmeric continues to
generate interest in universities and medical centers around the
world, with studies
and clinical trials exploring the many health benefits of the curcumin 95%
that we produce and supply. You will receive a
100% natural, additive-free product: no
synthetics, starch, no sugars or sweeteners, no artificial
colors or flavors, no sodium, no soy, no yeast, no wheat, no
corn, no rice or other grains, no gluten, no dairy, no
preservatives, no gums, no dyes, and no GMO.
For questions or comments, please
email support@turmeric-curcumin.com, call / text
206.339.7899
or mail
TURMERIC-CURCUMIN.COM
4031 Industrial Center Drive, North Las Vegas, NV 89031, USA.
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