Cancer, Curcumin and Ayurveda
Instead of concentrating on treating the symptoms of an illness,
ayurvedic medicine concentrates on treating the disease using
treatments to eliminate its root cause. According to Ayurveda,
cancer is a disease that is caused by lack of purpose, and is an
emotionally caused disease.
Ayurvedic science says that diet, lifestyles and medicine play an
important role in both the treatment and prevention of cancer.
Either too much, too little or wrong diets tend to affect the vata,
pitta and kapha of the body metabolism, and this in turn leads to
cancer. It is a group of chronic disorders that affect the different
dhatus and doshas which cause cancer.
Different people suffer from different forms of cancer, and its
diagnosis and treatment change according to the prakriti of the
patient. Treatment in Ayurveda for cancer consists in shodhan, which
is the detoxification and purification of dosha and dhatu, shaman
the pacification and rebalancing of the disturbed dosha and spoilt
dhatu and rasayana which is rejuvenation. Snehana which is internal
and external oiling of the body and swedan where sweating is induced
is suggested for shodhan of the body.
There is basically no specific treatment for cancer in Ayurveda.
Medication is used for restoring the normal functioning of organs of
the body and to help the body fight the disease. Though there are
some medicines that kill cancer cells, it is more of a supplemental
therapy that aims at an overall management of the disease. Positive
results have been reported with the use of heerak bhasma, which is
prepared with diamonds, for treating cancer.
With the help of Ayurved, it is possible to reduce reactions to
chemotherapy and radio therapy to an extent. A preparation of sea
coral called Praval pishti is cooling and helps in reducing the
intensity of the reactions in these procedures. However before
starting this, it is better to consult an ayurvedic doctor as
treatment changes from patient to patient.
It is possible to treat complaints like nausea and vomiting with
ayurvedic combinations of equal amounts of shredded ginger, honey
and lemon juice. This mixture should be taken before food to reduce
nausea and vomiting.
Ayurvedic therapy for treating cancer includes taking fresh
fruits and vegetables for natural vitamins and minerals, a light
diet that is easy to digest, fresh air, support from family and most
importantly, a positive attitude to life. Even ayurvedic tonics like
shatavari kalpa with asparagus, badam pak with almond and
Chyawanprash with amla help in coping with cancer.
Ayurvedic practitioners call turmeric the "golden spice of life."
Its botanical name is "Curcuma longa," and it belongs to the Ginger
family. Ayurveda, a 5,000 year old medical system, has used it for
healing, eating and more. Turmeric was used in its earliest days as
both a paste and a juice. When raw pieces of turmeric are crushed,
the result is a translucent, reddish-yellow tasteless liquid which
can be mixed with honey to give it some flavor. Turmeric liquid is
used in Ayurveda as a blood purifier, and in cases of chronic
illnesses and stomach problems. The paste is used to treat skin
conditions, like eczema.
Anticancerous Drug-Curcuma Longa Haldi(Circuma Longa), A Member Of
Ginger Family, Is Well Known Drug In Ayurveda. In Charak Samhita It
Is Catagorize Under Lekhniya,Vishaghna And Kushthaghna Mahakashaya.
In Sushrut Samhita It Is Catagorize Under Haridradi
Group.Bhavprakash Nighantu Described Haldi In Haritkyadi Group.
According Ayurveda,it Is Laghu , Ruksha In Guna,tikta In Rasa,
Katu In Vipaka And Ushna In Veerya.It Has Potent Raktashodhak(Purifies
The Blood- Means, It Removes All The Foreign Particles , Present In
The Blood) Property And Aam Pachak(Improves Metabolic Activity)
Activity. Astang Sangraha , An Ayurvedic Text Book,described That
Haldi Is Effective In Karkatarbud(Anti Cancerous Effect) .
Nearly All Ayurvedic Text Books Described Its Vat-shamak Effect
Due To Ushna Veerya And Useful In Skin Disorders. Chemical
Composition;- The Most Effective And Active Ingredient Of Haldi Is
Curcumin. It Is A Yellow Pigment.
Pharmacological Action: -
According Modern Researches, Curcumin, The Most Active Ingredient Of
Turmeric, Is A Powerful Antioxident Substance. It Has Also Anti-
Inflammatory Effect.It Inhibits Production Of The Inflammation
–related Enjyme- Cyclo-oxygenase2(Cox-2), Levels Of Which Are
Abnormally High In Certain Inflammatory Diseases. Curcumin Seems To
Protect Skin During Radiation Therapy.
According The Researches,carried Out By Ohio State University Of
Columbus,turmeric Has Demonstrated As Anticancerous Drug In All
States Of Tumour Development In Rodents And Showed Potential Effect
To Kill Cancer Cells And Prevent Normal Cells From Being Cancerous.
Researches Says That Whole Turmeric Ingested Through Diet Is Better
For Cancer Prevention Than Isolated Curcumin. Studies On Mice And
Humans Have Shown Potential Biological Activity As Turmeric To
Prevent Cancer. Through All Researches, It Seems That Turmeric Shows
A Lot Of Promise In Delaying The Onset Of Cancer.
Mode Of Action:-
Turmeric Shows Anticancerous Effect Through Probably 2 Ways. Frist,
As It Is Believe To Inhibit The Production Of Inflammatory Related
Enjyme Cyclo-oxygenase2(cox-2) Levels Of Which Are Abnormally High
In Certain Inflammatory Diseases And Cancers, Especially Bowel And
Colon Cancer. Secondly, It Inhibits Irreversibly Aminopeptidase
N(APN), An Enjyme That Is Responsible For Tumour Invasiveness And
Angiogenesis.(blood Vessel Growth). Scientists Have Known That
Curcumin Slows The Growth Of New Cancerous Cells. It Was Found To
Arrest Angiogenesis. APN Is A Membrane-bound, Zink Dependent
Metaloprotenase That Breaks Down Proteins At The Cell Surface And
Helps Cancer Cells Invade The Space Of Neighbouring Cells. Curcumin
Inhibits The APN Directly And Irreversibly.
Old and new interpretation of inflammation and cancer
Turmeric has always been considered an auspicious material in the
Indian sub-continent, both amongst the Aryan cultures and the
Dravidian cultures and its value extends far in history to the
beliefs of ancient Indian population. Yellow and yellow-orange are
colors with sacred and auspicious connotations in India, yellow
being associated with God, and as the color of the space between
chastity and sensuality. Orange signifies sacrifice, renunciation
and courage. In Buddhism yellow is the color of the Bodhisattva . In
South India, turmeric is considered very auspicious and therefore,
is the first item on the grocery list. The medicinal history of
turmeric is at least 2500 years old. Ayurveda, Unani, Siddha and
Chinese medicine recommend turmeric for a large number of disorders
and diseases. Susruta's Ayurvedic Compendium, dating to 250
BC, recommends an ointment containing turmeric to relieve the
effects of poisoned food.
Traditional Indian medicine use the powder against billary
disorders, anorexia, coryza, cough, diabetic wounds, hepatic
disorders, rheumatic disorders, sprains and swellings caused by
injury, and sinusitis. Externally, the dried rhizome has been
applied to fresh wounds and to insect stings and to help the healing
process in chickenpox and smallpox. Traditional Chinese medicine
uses curcuma in diseases associated with abdominal pain, amenorrhea,
dysmenorrheal, distending or pricking pain in the chest and abdomen;
impairment of consciousness in febrile diseases, epilepsy, and
mania; jaundice with dark urine.
Since the Ayurvedic times (1900 BC), numerous therapeutic
activities have been assigned to turmeric for a wide variety of
diseases and conditions, including those of the skin, pulmonary, and
gastrointestinal systems, aches, pains, wounds, sprains, and liver
disorders. Turmeric is also recommended under the Unani, Sidha and
Chinese systems of medicine. Modern research has confirmed and
provided a scientific basis for these various health claims, unlike
many other traditional medicines. Since the isolation of curcumin as
the main active constituent of turmeric about two centuries ago,
much of the scientific interest has shifted to this molecule rather
than on turmeric.
Observational studies point to the substantially reduced
prevalence of Alzheimer’s disease, rheumatoid arthritis and disease
of the gastrointestinal tract such as colon cancer and inflammatory
bowel diseases in Asian countries compared to the western world as a
consequence of the daily consumption of turmeric as a curry spice.
For this reason, curcumin has been termed “the spice of life”.
Research on curcumin is exploding with more than 3000 reports
presently available. This is because of an extremely wide array of
biological activities exhibited by the molecule. Curcumin acts at
multiple targets and at multiple levels. The number of transcription
factors and signaling pathways modulated by curcumin is, indeed,
bewildering1,2. For this reason, curcumin is fast emerging as a
cure-all, for valid reasons. Curcumin has demonstrated benefit for
most, if not all, chronic diseases afflicting mankind. It is an
antioxidant several times more potent than _-tocopherol and can
effectively scavenge oxygen- and nitrogen free radicals. It is a
complete anti-inflammatory modulating all the agents involved in the
complex process of inflammation, including cytokines, chemokines,
adhesion molecules, growth factors and transcription factors such ah
NF-KB and AP-1, and a large number of kinases, notably the MAP
kinases p38 and JNK. It is an inhibitor of histone
acetyltransferases3,4 thereby preventing the transcription of
inflammatory genes. In heart disease, curcumin can affect all the
steps believed to be involved in the pathologic process of
atherosclerosis. In diabetes, it can potentially reverse insulin
resistance, the first clinically relevant stage of the disease.
Further, it can sensitize insulin by inducing the transcription
factor PPAR_, similar to the thiazolidinediones currently used for
the purpose. Curcumin can be shown to be the only agent that can
effectively address all the multiple factors involved in Alzheimer’s
disease and rheumatoid arthritis. As an anticancer agent, it is a
chemo preventive, affect cell cycle progression and transformation,
cause apoptosis of malignant cells by more than one mechanism,
prevents angiogenesis and metastasis, and is effective even against
drug-resistant cancers. Whereas the present day cancer drugs are
specific for one type of cancer, curcumin has been shown in
preclinical studies to be effective against virtually all forms of
human cancers. While common chemotherapeutic agents cause serious
side effects, curcumin produces none. While the common anticancer
drugs are Immuno-suppressors, curcumin is an immuno-restorer5,6.
Furthermore, whereas the common anticancer drugs cannot cross the
bloodbrain barrier, curcumin can. Curcumin exhibits activities
similar to recently discovered drugs such as TNF inhibitors (e.g.,
Humira, Remicade, and Enbrel), a vascular endothelial cell growth
factor (VEGF) blocker (e.g., Avastin), human epidermal growth factor
receptor (EGFR) inhibitors (e.g., Erbitux, Erlotinib, and Geftinib),
and the HER2 blocker (e.g., Herceptin), minus their toxic side
Turmeric may contain well over a hundred chemical species, most
of these originating from the essential oil part of turmeric. A
complete analysis of all these constituents has not so far been
undertaken. However, the major and characteristic components of
turmeric are the three curcuminoids and volatile compounds of
turmeric. Curcuminoids: Curcumin, Desmethoxy curcumin,
Bisdesmethoxy curcumin Curcuminoids exist as a mixture of the keto-
and enol tautomeric forms, their relative composition dependent on
the pH of the medium.
The curcuminoids are diferuloylmethanes with curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)
-1,6- heptadiene-3,5-dione, see structure) as the main and the most
active constituent. Compounds lacking either one or two methoxy
groups in the aromatic rings (desmethoxycurcumin, and
bisdesmethoxycurcumin, respectively) form the other two constituents
of the curcuminoids fraction. Other functional groups, namely the
phenolic OH- group and -unsaturated diketo Michael acceptor
functions, are identical. The Michael acceptor property may be
considered crucial for most of curcumin’s biological activity, the
methoxy groups have apparently supportive roles in these activities
because compounds lacking these groups are less active, with
desmethoxycurcumin (lacking one methoxy group) being less active
than curcumin, and bisdesmethoxycurcumin, lacking both methoxy
groups, the least active. However, a recent report suggests that
bis-desmethoxycurcumin was the
most potent in correcting immune defects in AD patients1. The
Michael acceptor functionality allows
the curcuminoids to react or form complexes with a number of
molecules, notably proteins, both
covalently and non-covalently. For example, curcumin forms stable
complexes with serum albumin which may
be important in its transport within the human body.
A recent study2 compared the relative ant-inflammatory,
anti-proliferative, and antioxidant properties
of the three curcuminoids, along with tetrahydrocurcumin and
the turmerones. the relative potency for
suppression of tumor necrosis factor (TNF)-induced nuclear
factor-kappaB (NF-KB) activation was
curcumin > desmethoxycurcumin > bisdesmethoxycurcumin; thus
suggesting a critical role of methoxy
groups on the phenyl rings. Tetrahydrocurcumin, which lacks the
conjugated bonds in the central
seven-carbon chain, was completely inactive for suppression of the
transcription factor. Turmerones also
failed to inhibit TNF-induced NF-KB activation. The suppression of
NF-KB activity also correlated with
down-regulation of cyclooxygenase-2 (COX-2), cyclin D1 and vascular
endothelial growth factor (VEGF), all
regulated by NF-KB. In contrast to NF-KB activity, the suppression
of proliferation of various tumor cell
lines by the three curcuminoids was found to be comparable;
indicating the methoxy groups play
minimum role in the growth-modulatory effects of curcumin.
Tetrahydrocurcumin and turmerones were
also found to be active in suppression of cell growth but to a much
lesser extent than curcumin, DMC and
BDMC. The antioxidant potential of all the curcuminoids were
comparable, not influenced by the
The dark side of the curcumin story is its poor systemic
availability due to poor absorption from the intestines and rapid
metabolism of the compound in the body. This has largely curtailed
its progress from the lab to the clinic, and no clinical trials have
progressed beyond the phase I stage. All these have led to the
general impression that curcumin’s benefits are largely unrealizable
in the human body. Early experiments indicated that curcumin
undergoes transformation during absorption from the intestine.
www.curcumincare.com has resolved many of these issues
and that is why the formulation from
www.curcumincare.com showed its results in volunteers
just in 10 days. Other formulation when administered orally to rats
in a dose of 1 g/kg, curcumin was excreted in the feces to about
75%, while negligible amounts of curcumin appeared in the urine1.
Measurements of blood plasma levels and biliary excretion showed
that curcumin was poorly absorbed from the gut. No apparent toxic
effects were seen after doses of up to 5 g/kg. When intravenously
injected or when added to the perfusate of the isolated liver,
curcumin was actively transported into bile, against concentration
gradients of several hundred times. The major part of the absorbed
drug was, however, metabolized. In suspensions of isolated
hepatocytes or liver microsomes 90% of the added curcumin was
metabolized within 30 min. The authors concluded that in view of the
poor absorption, rapid metabolism and excretion of curcumin, it is
unlikely that substantial concentrations of curcumin occur in the
body after ingestion. This study, which appeared as early as 1978,
appears to summarize our current understanding of the metabolic fate
of curcumin in vivo. Later studies have more or less confirmed these
findings. Oral and intraperitoneal doses of [3H] curcumin led to the
fecal excretion of most of the radioactivity2. Intravenous and
intraperitoneal doses of [3H] curcumin were well excreted in the
bile of cannulated rats. The major biliary metabolites were
glucuronides of tetrahydrocurcumin and hexahydrocurcumin. The major
route of elimination of the label was the feces; the urinary
excretion of the label was very low regardless of the dose; however,
its metabolites, namely, glucuronide and sulfate, were present3.
After i.p. administration of curcumin (0.1 g/kg) to mice, about 2.25
μg/ml of curcumin appeared in the plasma
in the first 15 min4. One hour after administration, the levels of
curcumin in the intestines, spleen, liver, and kidneys were 177.04,
26.06, 26.90, and 7.51 μg/g, respectively.
Only traces (0.41 μg/g) were observed in
the brain at 1 h. Thus, in mice, absorption of curcumin appears to
be significantly higher compared to rats. The intestinal tract plays
an important role in the metabolic disposition of curcumin.
Accordingly, a study explored curcumin metabolism in the subcellular
fractions (cytosolic and microsomal) of human and rat intestinal
tissue, and compared it with metabolism in the corresponding hepatic
fractions5. Quantitatively, major differences were observed between
human and rat tissues. In humans, microsomal glucuronidation
occurred to a much higher level in the intestine than liver, while
the reverse was true in the case of rat. In the rat, dietary
curcumin yielded low drug levels in the plasma, between 0 and 12 nM,
whereas tissue concentrations of curcumin in liver and colon mucosa
were 0.1 to 0.9 nmol/g and 0.2 to 1.8 μmol/g,
respectively6. In comparison with dietary administration, suspended
curcumin given i.g. resulted in more curcumin in the plasma but much
less in the colon mucosa. The authors conclude that curcumin mixed
with the diet achieves drug levels in the colon and liver sufficient
to explain the pharmacological activities observed and suggest that
this mode of administration may be preferable for the
chemoprevention of colon cancer. A prospective phase-I study7
evaluated pharmacokinetics, toxicology and biologically effective
dose of curcumin in cancer patients. Curcumin was given orally for 3
months. Biopsy of the lesion sites was done immediately before and 3
months after starting curcumin treatment. The starting dose was 500
mg/day. If no toxicity _ grade II was noted in at least 3 successive
patients, the dose was then escalated to another level in the order
of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration
of curcumin in serum and urine was determined. A total of 25
patients were enrolled in this study. There was no treatment-related
toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume
of the drug was unacceptable to the patients. The serum
concentration of curcumin usually peaked at 1 to 2 hours after oral
intake of curcumin and gradually declined within 12 hours. The
average peak serum concentrations after taking 4,000 mg, 6,000 mg
and 8,000 mg of curcumin were clinically relevant at 0.51 ± 0.11
μM, 0.63 ± 0.06 μM
and 1.77 ± 1.87 μM, respectively. Urinary
excretion of curcumin was undetectable. This study demonstrated that
curcumin is not toxic to humans up to 8,000 mg/day when taken by
mouth for 3 months. In another phase I study8, 15 patients with
advanced colorectal cancer refractory to standard chemotherapies
consumed curcumin (0.45 to 3.6 g per day) for up to 4 months. Blood,
urine and feces were collected on days 1, 2, 8, and 29. Blood was
collected before dosing and after 0.5, 1, 2, 3, 6, and 8 h after
dose. Curcumin was detected in plasma samples taken 0.5 and 1 h
postdose from 3 patients consuming 3.6 g of curcumin daily, with a
mean concentration of 11.1 ± 0.6 nmol/L on day 1, 2, 8, and 29 of
intervention. Glucuronides and sulfates of curcumin were detected at
levels of 15.8 ±0.9 and 8.9 ± 0.7 nmol/L, respectively. Presence of
metabolites arising out of metabolic reduction, e.g.
hexahydrocurcumin, was not reported. They were apparently absent.
Curcumin and itsmetabolites, unexpectedly, were present in high
amounts in the urine of the 6 patients consuming 3.6 g curcumin
daily, but not in the urine of patients consuming lower doses. The
urinary levels varied between 0.1 and 1.3 μmol/L
(curcumin), 19 and 45 nmol/L (curcumin sulfate), and 210 and 510
nmol/L (curcumin glucuronide). This is the only study which found
unchanged curcumin in the urine. Considering that curcumin is
insoluble in water, this result needs reconfirmation. The quantities
excreted through feces amounted to 25 to 116 nmol/g dried feces. In
another trial, 12 patients with confirmed colorectal cancer received
curcumin at dose levels of 450, 1800, or 3600 mg per day (4 patients
per dose level) for 7 days prior to colectomy9. Samples of
peripheral blood were taken 1 h post dose and surgery was done 6-7 h
after the last dose of curcumin. Curcumin levels in the plasma of
patients were below the limit of quantization (3 nmol/L). Levels in
the normal and malignant tissues ranged from 7 to 20 nmol/g tissue.
Normal mucosa from the caecum and ascending colon contained more
curcumin than normal mucosa from the transverse, splenic flexure,
and the descending colon. In patients who had received 1800 or 3600
mg curcumin, the concentration of curcumin was 21.7±8.2 and 6.8±3.7
nmol/g in the right and left colon, respectively. This difference
was not reflected by curcumin levels in tumor tissue originating
from different sites of the bowel. Curcumin metabolites were not
detected in the plasma. Extracts of colorectal mucosa of 7 of the 8
patients who received 1800 or 3600 mg curcumin showed the presence
of curcumin sulfate, and two patients from the highest dose
indicated the presence of curcumin glucuronide. However, the
concentrations of these conjugates were very low at about 1 pmol/g
tissue. The results of this study thus suggest that a daily dose of
3.6 g curcumin achieves pharmacologically efficacious levels in the
colorectum. Curcumin’s metabolic fate is decided by the phase I, II
and III detoxifying enzymes. Curcumin is, simultaneously, a
substrate for these enzymes, an inducer of these enzymes, as well as
an inhibitor of these enzymes, depending on context. Curcumin was
shown to inhibit sulfotransferases28-30. Inhibition29,31-33, as well
as induction34,35, of UDP-glucuronosyl-transferase have been
described. A similar situation exits with glutathione S-transferase
(GST) another phase II enzyme, where again curcumin has been shown
to be an inhibitor as well as an inducer. The chemo preventive
action of curcumin significantly depends on the induction of these
enzymes. Inhibition of these enzymes is relevant in the context of
overcoming drug resistance in cancer chemotherapy. Thus, the
metabolism of curcumin may depend on many external factors, and
probably may explain the confusing results reported. Although some
questions remain unanswered regarding the pharmacokinetics of
curcumin in humans, there is no denying the fact that considerable
proportion of ingested curcumin is excreted through feces, and at
least about one-half of absorbed curcumin is metabolized. The
quantity of curcumin that reaches tissues outside the gut are
probably pharmacologically insignificant. These results have,
apparently, dampened the spirits of researchers and halted
curcumin’s progress from Phase 1 trials.
A number of curcumin analogues have been tested, but in most
cases they were found to be less effective than curcumin itself. One
exception has been dimethoxycurcumin1. This derivative was found to
be more bioavailable. Nearly 100% of curcumin, but < 30% of
dimethoxycurcumin was degraded in HT116 cells treated for 48 h, and
incubation with liver microsomes confirmed the limited metabolism of
dimethoxycurcumin. The absence of free phenolic groups in
dimethoxycurcumin probably prevents its conversion to glucuronide
and sulfate. Piperine, an inhibitor of glucuronosyltransferase,
administered along with curcumin has been found to significantly
enhance the plasma curcumin concentration in animals and in humans2.
However, piperine is toxic at least to experimental animals.
Curcumin formulated with lecithin was found to increase its
bioavailability in rats about 5-fold3. In contrast, curcumin
concentrations in the gastrointestinal mucosa after ingestion of the
formulation were somewhat lower than those observed after
administration of unformulated curcumin. Fluorometric data on the
association of curcumin with phosphatidylcholine indicate that one
molecule of curcumin could bind six molecules of
phosphatidycholine4. Thus, the formulated products would have low
curcumin content, and large amounts of lecithin would have to be
consumed in relation to the required curcumin dose.
www.curcumincare.com has been
working with Turmeric and curcimin since 2003. The scientists of
this company have achieved a major success to improve its activity
where no other formulation has been reported. The IC50 of this
formulation is less than 1micromole. The formulation has been used
by more than 200 volunteer and all been benefitted for their
inflammation and pain problems. A proposed clinical trial is on its
way for cancer prevention after chemotherapy . Another trial is also
proposed for arthritis and psoriasis.
Wahlstrom B, Blennow G, A study on the fate of
curcumin in the rat, Acta Pharmacol Toxicol (Copenh), 1978,
Ravindranath V, Chandrasekhara N, Metabolism of
curcumin--studies with [3H]curcumin, Toxicology, 1982, 22:337-44.
Ravindranath V, Chandrasekhara N, Absorption and
tissue distribution of curcumin in rats, Toxicology, 1980,16:259-65.
Pan MH, Huang TM, Lin JK, Biotransformation of
curcumin through reduction and glucuronidation in mice, Drug Metab
Disp, 1999, 27:486-94.
Ireson CR, Jones DJL, Orr S, et al. Metabolism of
the cancer preventive agent curcumin in human and rat intestine,
Biomarkers Prev, 2002, 11:105-11.
Sharma RA, Ireson CR, Verschoyle RD, et al.
Effects of dietary curcumin on glutathione S-transferase and
malondialdehyde-DNA adducts in rat liver and colon mucosa:
relationship with drug levels, Clin Cancer Res, 2001, 7:1452-58.
Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical
trial of curcumin, a chemopreventive agent, in patients with
high-risk or pre-malignant lesions, Anticancer Res, 2001,
Sharma RA, Euden SA, Platton SL, et al. Phase I
clinical trial of oral curcumin: biomarkers of systemic activity and
compliance, Clin Cancer Res, 2004, 10:6847-54.
Sharma RA, Euden SA, Platton SL, et al. Phase I
clinical trial of oral curcumin: biomarkers of systemic activity and
compliance, Clinical Cancer Res, 2004, 10:6847-54.
Garcea G, Berry DP, Jones DJL, et al.
Consumption of the putative chemopreventive agent curcumin by cancer
patients: assessment of curcumin levels
in the colorectum and their pharmacodynamic consequences, Cancer
Epidemiol Biomarkers Prev, 2005, 14:120-25.
Sharma RA, McLelland HR, Hill KA, et al.
Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in
patients with colorectal cancer, Clin Cancer Res, 2001, 7:1894-1900.
Lao CD, Ruffin MT 4th, Normolle D, et al. Dose
escalation of a curcuminoid formulation BMC Complement Altern Med,
Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical
trial of curcumin, a chemopreventive agent, in patients with
high-risk or pre-malignant lesions, Anticancer Res, 2001,
Cruz-Correa M, Shoskes DA, Sanchez P, et al.
Combination treatment with curcumin and quercetin of adenomas in
familial adenomatous polyposis, Clin Gastroenterol Hepatol, 2006,
Durgaprasad S, Pai CG, Vasanthkumar, et al. A
pilot study of the antioxidant effect of curcumin in tropical
pancreatitis, Indian J Med Res,2005, 122:315-18
Shoskes D, Lapierre C, Cruz-Correa M, et al.
Beneficial effects of the bioflavonoids curcumin and quercetin on
early function in cadaveric renal transplantation: a randomized
placebo controlled trial, Transplantation, 2005, 80:1556-59.
Holt PR, Katz S, Kirshoff R., Curcumin therapy in
inflammatory bowel disease: a pilot study, Dig Dis Sci, 2005,
Hanai H, Iida T, Takeuchi K, et al.
Curcumin maintenance therapy for ulcerative colitis:randomized,
placebocontrolled trail, Clin Gastroenterol Hepatol, 2006, 4:1502-06
Rasyid A, Rahman AR, Jaalam K, Lelo A. Effect of
different curcumin dosages on human gall bladder, Asia Pac J Clin
Nutr, 2002, 11:314-18.
Heng MC, Song MK, Harker J, Heng MK, et al.
Drug-induced suppression of phosphorylase kinase activity correlates
with resolution of psoriasis as assessed by clinical, histological
and immunohistochemical parameters, Br J Dermatol, 2000, 143:937-49.
Lal B, Kapoor AK, Asthana OP, et al. Efficacy of
curcumin in the management of chronic anterior uveitis, Phytother
Res, 1999, 13:318-22.
Prucksunand C, Indrasukhsri B, Leethochawalit M,
Hungsprengs K, Southeast Asian J Trop Med Public Health, 2001,
Di Mario F, cavallaro LG, Nouvenne A, et al. A
curcumin-based 1-week triple therapy for eradication of Heliobacter
pylori infection:something to learn from failure?, Heliobacter,
Nathan C, Points of control in inflammation,
Nature, 2002, 420:846-852.
Gilroy DW, Colville-Nash PR, Willis D, et al.
Inducible cyclooxygenase may have anti-inflammatory properties, Nat
Med, 1999, 5:698-701.
.Maslinska D, Kaliszek A, Operowska J, et
al. Constitutive expression of cyclooxygenase-2 (COX-2) in
developing brain. A. Charoid plexus in human fetuses, Folia
Neuropathol, 1999, 37:287-91.
Komhoff M, Wang JL, Cheng HF, et al.
Cyclooxygenase-2-selective inhibitors impair glomerulogenesis and
renal cortical development, Kidney Int, 2000, 57:414-22.
Kawai S, Cyclooxygenase selectivity and the risk
of gastrointestinal complications of various nonsteroidal
anti-inflammatory drugs: a clinical consideration, Inflamm Res,
1998, 47(suppl 2):S102-06.
Schmassmann A, Peskar BM, Stettler C, et al.
Effects of inhibition of prostaglandin endoperoxide synthase-2 in
chronic gastrointestinal ulcer models in rats, Br J Pharmacol,1998,
Katori M, Majima M, Cyclooxygenase-2: its rich
diversity of roles and possible application of its selective
inhibitors, Inflamm Res, 2000, 49:367-92.
Zhang X, Schwarz EM, Young DA, et al.
Cyclooxygenase-2 regulates mesenchymal cell differentiation into the
osteoblast lineage and is critically involved in bone repair, J Clin
Invest, 2002, 109:1405-15.
Simon AM, Manigrasso MB, O’Connor JP, et al.
Cyclooxygenase 2 function is essential for bone fracture healing, J
Bone Miner Res, 2002,17:963-76.
Li J, Burr DB, Turner CH, Suppression of
prostaglandin synthesis with NS-398 has different effects on
endocortical and periosteal bone formation induced by mechanical
loading, Calcif Tissue Int, 2002, 70:320-29.
Tang C-H, Yang R-S, Huang T-H, et al. Ultrasound
stimulates cyclooxygenase-2 expression and increases bone formation
through integrin, FAK, phosphatidylinositol 3-kinase and Akt pathway
in osteoblasts, Mol Pharmacol, 2006, 69:2047-57.
Li L, Pettit AR, Gregory LS, Forwood MR,
Regulation of bone biology by prostaglandin endoperoxidase H
synthase (PGHS): a rose by any other name…, Cytokine Growth Factor
Rev, 2006, 17:203-16.
Lim H, Paria BC, Das SK, Multiple female
reproductive failures in cyclooxygenase 2-deficient mice, Cell,
Davis BJ, Lennard DE, Lee CA, et al. Anovulation
in cyclooxygenase-2-deficient mice is restored by prostaglandin E2
and interleukin-1beta, Endocrinology, 1999, 140:2685-95.
Sirois J, Sayasith, Brown KA, et al.
Cyclooxygenase-2 and its role in ovulation: a 2004 account, Hum
Reprod Update, 2004, 10:373-85.
Gaytan M, Morales C, Bellido C, et al.
Non-steroidal anti-inflammatory drugs (NSAIDs) and ovulation:
lessons from morphology, Histol,
Histopathol, 2006, 21:541-56.
Ostensen ME, Skomsvoll JF, Anti-inflammatory
pharmacotherapy during pregnancy, Expert Opin Pharmacother, 2004,
Stanfield KM, Bell RR, Lisowski AR, et al.
Expression of cyclooxygenase-2 in embryonic and fetal tissues during
organogenesis and late pregnancy, Birth Defects Res A Clin Mol
Teratol, 2003, 67:54-58.
Goldberg RJ, Spencer FA, Steg PG, ret al.
Increasing use of single and combination medical therapy in patients
hospitalized for acute myocardial infarction in the 21st century,
Arch Intern Med, 2007, 167:1766-73.
Moore TJ, Cohen MR, Furberg CD, Serious adverse
drug events reported to the food and drug administration, 1998-2005,
Arch Intern Med, 2007, 167:1752-59.
Fiala M, Liu PT, Espinosa-Jeffrey A, et al.
Innate immunity and transcription of MGAT-III and toll-like
receptors in Alzheimer’s disease patients are improved by
bisdemthoxycurcumin, Proc Natl Acad Sci USA, 2007, 104:12849-54.
Sandur SK, Pandey MK, Sung B, et al. Curcumin,
demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and
turmerones differentially regulate anti-inflammatory and
anti-proliferative responses through a ROS-independent mechanism,
Carcinogenesis, 2007, 28:1765- 73.
Aggarwal BB, Shishodia S, Molecular targets of
dietary agents for prevention and therapy of cancer, Biochem
Pharmacol, 2006, 71:1397- 1421.
Aggarwal BB, Sundaram C, Malani N, Ichikawa H,
Curcumin: the Indian solid gold, Adv Exp Med Biol, 2007, 595:1-75.
Balasubramanyam K, Varier RA, Altaf M, et al.
Curcumin, a novel p300/CREB-binding protein-specific inhibitor of
acetyl transferase, repress the acetylation of histone/nonhistone
proteins and histone acetyltransferase-dependent chromatin
transcription, J Biol Chem, 2004, 279:51163-71
Marcu MG, Jung YJ, Lee S, et al. Curcumin is an
inhibitor of p300 histone acetyltransferase, Med Chem, 2006,
Jagetia GC, Aggarwal BB, “Spicing up” the immune
system by curcumin, J Clin Immunol, 2007, 27:19-35.
Bhattacharyya S, Mandal D, Sen GS, et al.
Tumor-induced oxidative stress perturbs nuclear factor-kappaB
activity-augmenting tumor necrosis factor-alpha-mediated T-cell
death: protection by curcumin, Cancer Res, 2007, 67:362-70.
Gautam SC, Gao X, Dulchavsky S, Immunomodulation
by curcumin, Adv Exp Med Biol, 2007, 595:321-41
Akamine H, Hossain MA, Ishimine Y, et al. Effects
of application of N, P and K alone or in combination on growth,
yield and curcumin content of turmeric (Curcuma longa L.), Plant
Prod Sci, 2007, 10:151-54.
Bos R, Windono T, Woerdenbag HJ, et al.
HPLC-photodiode array detection analysis of curcuminoids in curcuma
species indigenous to Indonesia, Phytochem Anal, 2007, 18:118-22.
Garg SN, Bansal RP Gupta MM, Kumar S, Variation
in the rhizome essential oil and curcumin contents and oil quality
in the land races of turmeric Curcuma longa of North Indian plains,
Flav Fragr J, 1999, 14:315-18.
Tamvakopoulos C, Dimas K, Sofianos ZD, et al.
Metabolism and anticancer activity of curcumin analogue,
dimethoxycurcumin, Clin Cancer Res, 2007, 13:1269-77.
Shoba G, Joy D, Joseph T, et al. Influence of
piperine on the pharmacokinetics of curcumin in animals and human
volunteers, Planta Med, 1998, 64:353-56.
Marczylo TH, Verschoyle RD, Cooke DN, et al.
Comparison of systemic availability of curcumin with that of
curcumin formulated with phosphatidylcholine, Cancer Chemother
Pharmacol, 2007, 60:171-77.
Began G, Sudharshan E, Udaya sankar K, Appa Rao
AG, Interaction of curcumin with phosphatidylcholine: a
spectrofluorometric study, J Agric Food Chem,1999, 47:4992-97.
Antony B, A composition to enhance the
bioavailability of curcumin, WO2006129323 (2006) to Arjuna Natural
Lantz RC, Chen GJ, Solyom AM, et al. The effect
of turmeric extracts on inflammatory mediator production,
Phytomedicine, 2005, 12:445- 52.
Nishiyama T, Mae T, Kishida H, et al.
Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.)
suppress an increase in blood glucose level in type 2 diabetic KK-Ay
mice, J Agric Food Chem, 2005, 53:959-63.
Li L, Ahmed B, Mehta K, Kurzrock R, Liposomal
curcumin with and without oxaliplatin: effects on cell growth,
apoptosis, and angiogenesis in colorectal cancer, Mol Cancer Ther,
unwar A, Barik A, Pandey R, Priyadarshini KI,
Transport of liposomal and albumin loaded curcumin to living cells:
an absorption and fluorescence spectroscopic study, Biochim Biiophys
Acta, 2006, 1760:1513-20.
ung S, Orberg N, Thiede G, et al. Innovative
liposomes as a transfollicular drug delivery system: penetration
into porcine hair follicles, J Invest Dermatol, 2006, 126:1728-32.
i L, Bratiteh FS, Kurzrock R,
Liposome-encapsulated curcumin: In vitro and in vivo effects on
proliferation, apoptosis, signaling, and angiogenesis, Cancer, 2005,
umar V, Lewis SA, Mutalik S, et al. Biodegradable
microspheres of curcumin for treatment of inflammation, Indian J
Physiol Pharmacol, 2002, 46:209-17.
arkatou E, Gionis V, Chryssikos GD, et al.
Molecular interactions between dimethoxycurcumin and Pamam dendrimer
carriers, Int J Pharm, 2007, Mar 12; Epub ahead of print; PMID
17428628. isht S, Feldmann G, Soni S, et al. Polymeric nanoparticle-encapsulated
curcumin (nanocurcumin): a novel strategy for human cancer therapy,
J Nanobiotechnol, 2007, 5:3.
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