Curcumin, the compound responsible for the yellow color of turmeric has much more to offer than just its color. Curcumin comes with a plethora of health benefits which makes it a hot topic in the nutraceutical industry. Unleash the world of curcumin and see the reasons why you need to spice it up!
2. The Indian Solid Gold
• Curcumin is extracted from turmeric which is derived from rhizome of the plant
Curcuma longa
• Curcuminoids give turmeric its characteristic yellow color
• Curcumin ( ): is an orange-yellow crystalline powder which is the most active
component of turmeric, which makes up 2-5% of the spice
• Curcumin has been shown to be a diferuloylmethane
• It is hydrophobic in nature and is soluble in dimethylsulfoxide, acetone, ethanol and oils
• It is also referred to as Indian saffron, yellow ginger, yellow root, kacha haldi, ukon or
natural yellow 3
12 20 6C H O
3. Chemical Composition
• Insoluble in water & ether
• Soluble in ethanol, dimethylsulfoxide & acetone
• Has a melting point of 183°C
• Molecular formula :
• Molecular weight: 368.37g/mol
• Turmeric contains curcumin along with other constituents
known as “curcuminoids”
Curcumin (Curcumin I)
Demethoxycurcumin (Curcumin II)
Bisdemethoxycurcumin (Curcumin III)
Cyclocurcumin
• Commercial curcumin contains curcumin I (~77%),
curcumin II (~17%) & curcumin III (~3%)
• Curcumin has a brilliant yellow hue at pH 2.5 & takes a red
hue at pH>7
12 20 6C H O
4. Food sources
Major source of curcumin obtained from Curcuma longa & is used as a
spice in Indian, South Asian, Middle Eastern cuisines. Curry
powders have variable and relatively low amount of curcumin.
Curcuma aromatica, Curcuma phaeocaulis (3%), Curcuma
zedoaria (0.1%), Curcuma mangga, Curcuma xanthorrhiza (1-2%),
Costus speciosus, Zingiber cassumunar, Etlingera elatior
Curcumin extracts used as dietary supplements are standardized to
contain 95% curcuminoids (not strictly regulated by US FDA).
Curcumin extracts are also used as food-coloring agents.
TURMERIC
OTHER
PLANTS
EXTRACTS
6. METABOLISM OF CURCUMIN
• Once absorbed, curcumin is subjected to sulfation
and glucuronidation at various tissue sites
(majorly, liver)
Major biliary metabolites: Glucuronides of
tetrahydrocurcumin (THC) & hexahydrocurcumin
(HHC)
Minor metabolites: Dihydroferulic acid together with
traces of ferulic acid
• Orally administered curcumin is absorbed from the
alimentary tract and present in the general blood
circulation after largely being metabolized to the form
of glucuronide/sulfate conjugates
• There is no clear understanding on whether curcumin
metabolites are as active as curcumin
• Some studies found that THC showed better anti-
diabetic & antioxidant activity in type 2 diabetes
& much lower anti-inflammatory & anti-
7. BIOAVAILABILITY OF CURCUMIN
SERUM CONCENTRATIONS
• Curcumin is poorly absorbed
from the gut
ORAL: Admin. of 1.0g/kg showed
low plasma levels (0.13µg/mL)
after 15min, max. plasma level
(0.22µg/mL) after 1h, which then
declined below detection limit by
6h
I.V/I.P: Plasma levels peaked
(2.25µg/mL) within 15min of
admin. & declined rapidly within
1h
TISSUE DISTRIBUTION
• Oral admin. of 400mg showed that only
traces of unchanged drug was found in
the liver & kidney and 90% was found in
the stomach after 30min which was
reduced to 1% after 1h
• The percentage of curcumin absorbed
(60-66%) remained constant regardless of
the dose
• I.P route showed max. amount of
curcumin in the intestine after 1h; spleen,
liver & kidney showed moderate amounts
whereas only a trace amount was found in
HALF LIFE
• It was reported that when 1g/kg
curcumin was given orally to
rats, 75% of it was excreted in
feces & negligible amounts
were found in urine
• The absorption & elimination
half-lives of orally administered
curcumin in rats was found to be
0.31 & 1.7h respectively
• Half-lives in humans were not
found since the serum levels
were below the detection limits
8. STABILITY OF CURCUMIN
• Curcumin is unstable at neutral and basic pH
& is degraded to ferulic acid & feruloyl methane
• More than 90% of the curcumin decomposes
rapidly in buffer systems at neutral-basic pH &
this degradation occurs due to oxidative
mechanism
• Curcumin is also unstable in phosphate buffer at
pH 7.4
• Curcumin is expected to be stable in stomach
and small intestines since the pH is between 1
to 6 & the degradation is really slow in these
conditions
• Curcumin exists in polar solvent as keto-enol
tautomer & as diketo tautomer in non-polar
solvents
9. The poor absorption from the intestine, coupled with high degree
of metabolism of curcumin in the liver and it’s rapid elimination in
the bile, makes it unlikely that high concentrations of the
substance would be found in the body long periods of time after
ingestion
11. ANTIOXIDANT ACTIVITY
• Curcumin is known to protect biomembranes against
peroxidative cell membrane damage (free-radical-mediated
chain reaction)
• The inhibition of peroxidation by curcumin is mainly
attributed to the scavenging of the reactive free radicals
involved in the peroxidation.
• Theoretical calculations have shown that the enol form of
curcumin is more stable than the keto form and the BDE of
the phenolic O-H bond is significantly lower than that of the
central O-H,suggesting that the hydrogen atom extraction
takes place at the phenolic group
• Litwinienko and Ingold recently proposed the sequential
proton loss electron transfer theory (SPLET) in ionizing
solvents and H-Atom Transfer (HAT) mechanism in non-
ionizing solvents
12. ANTI-INFLAMMATORY ACTIVITY
• The anti-inflammatory effect of curcumin is most likely mediated through its ability to
inhibit cyclooxygenase-2 (COX-2), lipoxygenase (LOX), and inducible nitric oxide
synthase (iNOS).
Effect of Curcumin on Cyclooxygenases and Lipoxygenases
• Curcumin suppresses prostaglandin (PG) synthesis. PG is involved in human cancer
development (carcinogen metabolism, tumour cell proliferation). COX is a key
enzyme responsible for conversion of arachidonic acid (AA) to PGs. AA metabolites
derived from LOX pathways play an important role in growth related signal
transduction (contributing to cancer development). Curcumin is shown to inhibit both
COX and LOX activities
Effect of Curcumin on Inducible Nitric Oxide Synthase
• iNOS catalyzes the oxidative deamination of L-arginine to produce NO, a potent
pro-inflammatory mediator. NO has multifaceted roles in mutagenesis and
carcinogenesis.NO reacts rapidly with superoxide anion to produce peroxynitrite
(ONOO-) which can cause harmful DNA modifications and actiavtes the tumout
suppressor gene p53 or PARP which is associated with apoptic cell death. iNOS
also regulates COX-2 Curcumin has been shown to inhibit iNOS gene expression.
13. GLUTATHIONE SYNTHESIS
• Glutathione is an important intracellular antioxidant that
plays a critical role in cellular adaptation to stress.
• Stress-related increases in cellular glutathione levels
result from increased expression of glutamate cysteine
ligase (GCL), the rate-limiting enzyme in glutathione
synthesis.
• Studies in cell culture suggest that curcumin can
increase cellular glutathione levels by enhancing the
transcription of genes that encode GCL
14. CANCER
• Because inflammation is closely linked to tumor promotion,
curcumin with its potent anti-inflammatory property is anticipated
to exert chemopreventive effects on carcinogenesis
• Curcumin has been shown to protect against skin, oral, intestinal,
and colon carcinogenesis and also to suppress angiogenesis and
metastasis in a variety animal tumor models
• It also inhibits the proliferation of cancer cells by arresting them in
the various phases of the cell cycle and by inducing apoptosis
• Curcumin has a capability to inhibit carcinogen bioactivation via
suppression of specific cytochrome P450 isozymes, as well as to
induce the activity or expression of phase II carcinogen
detoxifying enzymes.
15. CANCER
Effects on biotransformation enzymes involved in carcinogen
metabolism
• Biotransformation enzymes play important roles in the metabolism and
elimination of a variety of biologically active compounds, including drugs
and carcinogens.
• In general, phase I enzymes, including those of the cytochrome P450
(CYP) family, preparing them for reactions catalysed by phase II
biotransformation enzymes. Dietary curcumin increases the activity of
phase II enzymes
Induction of cell cycle arrest and apoptosis
• Defective cell-cycle regulation may result in the propagation of mutations
that contribute to the development of cancer. Curcumin has been found to
induce cell-cycle arrest and apoptosis in a variety of cancer cell lines
grown in culture (1, 31-35). The mechanisms by which curcumin induces
apoptosis are varied but may include inhibitory effects on several cell-
signalling pathways
Inhibition of tumor invasion and angiogenesis
• Cancerous cells invade normal tissue with the aide of enzymes called
matrix metalloproteinases. Curcumin has been found to inhibit the activity
of several matrix metalloproteinases in cell culture studies. To fuel their
rapid growth, invasive tumors must also develop new blood vessels by a
process known as angiogenesis. Curcumin has been found to inhibit
angiogenesis in cultured vascular endothelial cells and in an animal model
16. CYSTIC FIBROSIS
• Cystic fibrosis is a hereditary disease caused by mutations in
the cystic fibrosis transmembrane conductance regulator
(CFTR) gene.
• CFTR is a transmembrane protein that acts as a chloride
channel and plays a critical role in ion and fluid transport.
• In the lungs, CFTR mutations ultimately result in increased
mucus concentration and decreased mucus clearance, which
leads to progressive lung disease.
• In 2004, a study in mice with the DeltaF508 mutation found
that oral curcumin administration corrected abnormal ion
transport and improved the survival of these mice.
• However, it is unclear whether curcumin supplementation will
be of benefit to humans with cystic fibrosis.
17. ALZHEIMER’S DISEASE
• In Alzheimer’s disease, a peptide called amyloid β forms
aggregates (oligomers), which accumulate in the brain and form
deposits known as amyloid plaques.
• Inflammation and oxidative damage are also associated with the
progession of Alzheimer’s disease.
• Curcumin has been found to inhibit amyloid β oligomer formation in
vitro.
• When injected peripherally, curcumin was found to cross the blood
brain barrier in an animal model of Alzheimer’s disease.
• In animal models of Alzheimer's disease, dietary curcumin has
decreased biomarkers of inflammation and oxidative damage,
amyloid plaque burden in the brain, and amyloid β-induced
memory deficits
• It is not known whether curcumin taken orally can cross the blood
brain barrier or inhibit the progression of Alzheimer’s disease in
humans
18. ANTI-HIV ACTIVITY
• Curcumin inhibits the LTR (Long Terminal Repeat ),
a sequence of viral HIV DNA which activates the
viral genome.
• Proposed mechanisms are:
1. Prevent the binding at its DNA binding site.
2. It may inhibit protein kinase C (HIV protease
enzyme)
19. SKIN DISEASES
• Curcumin protects skin by quenching free radicals
and reducing inflammation through nuclear factor-
kB inhibition.
• Curcumin treatment also reduced wound healing
time, improved collagen deposition and increased
fibroblast and vascular density in wounds thereby
enhancing both normal and impaired wound-
healing.
• Curcumin has also been shown to have beneficial
effect as a proangiogenic agent in wound-healing
by inducing transforming growth factor-kB, which
induces both angiogenesis and accumulation of
extracellular matrix, which continues through the
remodeling phase of wound repair.
20. EXTRACTION OF CURCUMIN FROM
TURMERIC
Various approaches have been followed on the extraction or isolation of
curcumin from turmeric.
Solvent extraction (the most conventional method)
Supercritical CO2 extraction
Ultra-sonic irradiation (40% curcumin yield)
Microwave extraction (68.75% curcumin yield)
Water soaked irradiation (71.42% curcumin yield)
21. SOLVENT EXTRACTION OF
CURCUMIN
The extraction process is carried out in two steps- selective removal of the turmeric oil and extraction
of pigments
1. Rhizome is de-oiled by hexane, which has a poor selectivity for coloring matter
2. The residue is then freed from the solvent & exhaustively extracted with another solvent like
methanol to recover curcumin. After removing the solvent, the concentrated extract is dissolved in
alkali, filtered & acidified with acid to precipitate the pigment
Powdering
Solvent
extractio
n
Partial
concentratio
n
Crystallization
Removal of
crystals by
centrifugatio
n
Purification
of crystals
by washing
Solvent
removal
by steam
DryingPowdering
TURMERIC
CURCUMIN
22. DRUG-DRUG INTERACTIONS
TYPE OF DRUG MECHANISM EXAMPLES
Anticoagulant/ Antiplatelet Inhibit platelet aggregation
suggesting a potential for
curcumin supplementation to
increase the risk of bleeding in
people taking these drugs
Aspirin, Clopidogrel (Plavix),
Dalteparin (Fragmin),
Enoxaparin (Lovenox), Heparin,
Ticlopidine (Ticid) & Warfarin
(Coumadin)
Chemotherapeutic agents in
Breast cancer
Inhibits apoptosis induced by
these agents. Dietary curcumin
was found to inhibit
cyclophosphamide-induced
tumor regression.
Camptothecin, Mechlorethamine,
Doxorubicin
23. CURCUMIN + PIPERINE = A PERFECT
MATCH
Piperine has been found to increase the bioavailability &
absorption of curcumin in both rats and humans with no
adverse effects
• Upon oral administration of curcumin with piperine, curcumin could be found in
blood even up to 8 days
• The amounts of curcumin present in blood, liver tissue, kidney & brain tissue
were found to be higher than what is found when curcumin is administered alone
• Excretion of intact curcumin in the urine was relatively higher compared to
what was seen when curcumin was administered alone & accounted for 1.43%
of the dose administered
• Serum concentrations of curcumin were found to be higher
• Bioavailability increased by 154% whereas elimination half life & clearance
decreased significantly
• The extent of absorption of curcumin when taken with piperine (humans) is 78%
compared to 63.5% absorption observed when administered alone
24. SAFETY AND TOXICOLOGY
• Has GRAS status in the USA.
• Serious adverse effects have not been reported in humans taking high
doses of curcumin.
• A dose escalation trial in 24 healthy adults found that single oral
dosages up to 12 g were safe, and adverse effects were not dose-
related.
• 20-40 mg supplementation reported to increase gallbladder
contractions in healthy people.
• Mild nausea and diarrhoea experienced by two participants in a UK
based clinical trial where curcumin supplementation of 0.45-3.6 g/ day
was given for 4 months to cancer patients.
• The maximal tolerated dose, a traditional end point for anticancer
chemotherapy, of curcumin has not been reached in these studies.
25. SAFETY AND TOXICOLOGY
• Pregnancy and lactation
While studies in pregnant rats, mice, guinea pigs, and monkeys suggested that the use of
turmeric or curcumin is safe for those animals in pregnancy, there have been no studies involving
pregnant women subjects reported to date.
• Based on studies on possible interactions of turmeric with other herbs or medicines, it can be
advised that turmeric (or curcumin supplements) should not be used in the following
circumstances without prior consultation with a qualified medical practitioner:
1. People who are on blood thinning medications, e.g., warfarin, aspirin, etc.
2. People who are on nonsteroidal anti-inflammatory drugs, e.g., indomethacin, ibuprofen, etc.
3. People who are on the hypotensive drug, reserpine.