Biological activityOf

Turmeric

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By Omer Bayazeid

Curcuma longa

Introduction

Structure AND

General Information

Curcumin is the chief component of the

spice turmeric and is derived from the rhizome of the East Indian plant Curcuma longa. Curcuma longa is a member of the Zingiberacae (ginger) family of botanicals and is a perennial plant that is native to Southeast Asia.Turmeric contains a class of compounds known as the curcuminoids, comprised of curcumin, demethoxycurcumin and bisdemethoxycurcumin.

Curcumin is the principal curcuminoid and

comprises approximately 2-5% of turmeric; it is responsible for the yellow color of the spice as well as the majority of turmeric's therapeutic effects. Aside from being employed as a flavoring and coloring agent in food, turmeric has also been widely used in old Indian medicine for its anti-oxidant, antiseptic, analgesic, antimalarial and anti-inflammatory properties. Curcumin has been consumed as a dietary supplement for centuries and is considered pharmacologically safe.

Three main curcuminoid

s were isolated

from turmeric:

Biological Activities of curcumin

(1) Anti-inflammatory activity. (8) Antidiabetic effect.

(2) Antioxidant effect. (9) Antibacterial activity.

(3) Antivenom effect. (10) Antifungal effect.

(4) Anticarcinogenic effect. (11) Antiprotozoan activity.

(5) Pro/antimutagenic activity. (12) Antiviral effect.

(6) Anticoagulant activity. (13) Antifibrotic effect.

(7) Antifertility activity.

Anticarcinogenic effect induction of apoptosis

Curcumin acts as a potent anti-carcinogenic compound. Among various mechanisms, induction of apoptosis plays an important role in its ant carcinogenic effect.

It induces apoptosis and inhibits cell-cycle progression, both of which are instrumental in preventing cancerous cell growth in rat aortic smooth muscle cells.

The mechanisms for anticancer effects are multiple:

• Antiproliferative effects:

Is mediated partly through inhibition of protein tyrosine kinase and c-myc mRNA expression and the apoptotic effect may partly be mediated through inhibition of protein tyrosine kinase, protein kinase C, c-myc mRNA expression and bcl-2 mRNA expression.

Curcumin induces apoptotic cell death by DNA-damage in human cancer cell lines, TK-10, MCF-7 and UACC-62 by acting as topoisomerase II poison.

• Suppression of cyclooxygenase-2 (COX-2) and lipooxygenase expression, which blocks production of prostaglandins and leukotrienes, respectively.

• Suppression of cyclin D1 which is a proto-

oncogene overexpressed in many cancers (e.g., breast, esophagus, lung, liver, head and neck, colon, and prostate).

• Suppression of adhesion molecules that play an

important role in tumor metastasis.

• Suppression of various inflammatory cytokines, including tumor necrosis factor.

• Suppression of angiogenesis, a crucial step in the growth and metastasis of many cancers.

• Competition with carcinogens that use the aryl hydrocarbon and cytochrome P450 pathway.

However, curcumin affects different cell lines differently. Whereas leukaemia, breast, colon, hepatocellular and ovarian carcinoma cells undergo apoptosis in the presence of curcumin, lung, prostate, kidney, cervix and CNS malignancies and melanoma cells show resistance to cytotoxic effect of curcumin.

Curcumin also suppresses tumour growth

through various pathways.

Nitric oxide (NO) and its derivatives play a major role in tumour promotion. Curcumin inhibits iNOS and COX-2 production by suppression of NFkB activation. Curcumin also increases NO production in Natural Killer (NR) cells after prolonged treatment, culminating in a stronger tumouricidal effect. Curcumin also inhibits proliferation of rat thymocytes.

These strongly imply that cell growth and

cell death share a common pathway at some point and that curcumin affects a common step, presumably involving modulation of AP-1 transcription factor.

Numerous animal and in vitro studies have demonstrated the ability of turmeric and It’s active component, curcumin, to suppress the growth of a variety of tumor cells.

Anti-inflammatory activity

• The antirheumatic activity of curcumin has been established in patients who showed significant improvement of symptoms after administration of curcumin.

• Curcumin stimulates stress-induced

expression of stress proteins and may act in a way similar Curcumin offers antiinflammatory effect through inhibition of NFkB activation.

• Curcumin is effective against carrageenin-induced oedema in rats and mice. The natural analogues of curcumin, viz. FHM and BHM, are also potent anti-inflammatory agents. The volatile oil and also the petroleum ether, alcohol and water extracts of C. longa show anti-inflammatory effects.

• The anti-rheumatic activity of curcumin has also been established in patients who showed significant improvement of symptoms after administration of curcumin. That curcumin stimulates stress-induced expression of stress proteins and may act in a way similar to indomethacin and salicylate, has recently been reported.

• Curcumin offers anti-inflammatory effect through inhibition of NFkB activation. Curcumin has also been shown to reduce the TNF-a-induced expression of the tissue factor gene in bovine aortic-endothelial cells by repressing activation of both AP-1 and NFkB.

• The anti-inflammatory role of curcumin is also mediated through down regulation of cyclooxygenase-2 and inducible nitric oxide synthetase through suppression of NFkB activation.

• Curcumin also enhances wound-healing in diabetic rats and mice, and in H2O2-induced damage in human keratinocytes and fibroblasts.

Antioxidant effect activity

• The antioxidant activity of curcumin was reported as early as 1975.

• It acts as a scavenger of oxygen free radicals. It can protect hemoglobin from oxidation.

• In vitro, curcumin can significantly inhibit the generation of reactive oxygen species like superoxide anions, H2O2 and nitrite radical generation by activated macrophages, which play an important role in inflammation.

• It also decreases lipid per-oxidation in rat liver microsomes, erythrocyte membranes and brain homogenates.

• This is brought about by maintaining the activities of antioxidant enzymes like superoxide dismutase, catalase and glutathione peroxidase.

• Recently, it have been observed that curcumin prevents oxidative damage during indomethacin-induced gastric lesion not only by blocking inactivation of gastric peroxidase, but also by direct scavenging of H2O2 and •OH.

• Curcumin has the potential to control

diseases through its potent antioxidant activity.

Laboratory Studies

Curcumin has been shown to promote apoptosis in certain cancer cell lines, and to inhibit telomerase activity, an important factor in tumorigenesis.

One possible mechanism for the induction of tumor cell death is through the generation of reactive oxygen intermediates.

Although curcumin is the acknowledged active principal

in turmeric, the oleoresin of turmeric (after extraction of curcumin) also was found to have antimutagenic properties, thought to be mediated through its antioxidant action.

The anti-inflammatory properties of curcumin are thought to be due in part to suppression of prostaglandin synthesis.

Prostaglandin synthesis from arachidonic acid is catalyzed by two isoenzymes: COX-1 and COX-2, both found in colon tumors of rodents and humans. It has been found that curcumin significantly inhibited expression of COX-2 in human colon cancer cells and in COX-2 non-expressing cell lines, without altering the expression of COX-1.

This is an important benefit of curcumins since chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and non-specific inhibition of COX-1 lead to undesirable gastrointestinal and renal side effects.

Curcumin also was shown to inhibit the growth of Helicobacterpylori, a group 1 carcinogen, as a possible explainingmmechanism for its role in prevention of gastric and colon cancers in rodents.

Curcumin inhibition of the generation of reactive oxygen species (ROS) might interfere with the efficacy of chemotherapeutic drugs that induce apoptosis through the generation of ROS and the JNK pathway.

Studies in tissue culture showed that curcumin did inhibit the induction of apoptosis by several agents (camptothecin, mechlorethamme, and doxorubicin).

This effect was done- and time-dependent, but occurred after even brief three-hour exposures. In their in vivo model of human breast cancer, curcumin supplementation significantly inhibited cyclophosphamide-induced tumor regression and decreased activation of JNK and apoptosis.

Human Clinical Studies

In a Phase I clinical trial, curcuma extracts (containing 36-180 mg of curcumin) to 15 patients with refractory colorectal cancer.

The curcuma extracts were well-tolerated orally and no dose-limiting toxicity was observed.

Radiologically stable disease was demonstrated in five patients during 2-4 months of treatment.

The study showed that curcuma extract can be safely administered in doses of up to 2.2 g/d (180 mg of curcumin), has low oral bioavailability in humans, and may undergo intestinal metabolism.

It been examining that the anticancer effect of turmeric/curcumin reported a study of 25 patients with one of five high-risk conditions: recently resected bladder cancer, arsenic Bowen's disease of the skin,and intestinal metaplasia of the stomach.

Curcumin was administered orally for three months with doses ranging

from 500 to 12,000 mg/d. Curcumin was found to be non-toxic in doses of up to 8,000 mg/d orally for three months.

The results also showed that one of two patients with bladder cancer, two of seven patients with leucoplakia, one of six patients with intestinal metaplasia, and two of six patients with Bowen's disease developed frank malignancies in spite of treatment with curcumin.

Turmeric has been given to 16 chronic smokers in doses of 1.5 g/d for 30 days reduced the urinary excretion of mutagens in a controlled trial. There was no change in mutagen excretion in the urine of controls.

Although suggestive, measuring surrogate outcomes, such as urinary mutagens, does not necessarily correlate with reduction in cancer incidence.

In a follow-up to pharmacological research on the effects of curcumin on HIV cell replication, 18 HIV-positive patients were given an average dose curcumin of 2 g/d for 127 days.

There was a significant increase in CD4 and CD8 lymphocyte counts. The subsequent phase I/II study using doses of 2.7-4.8 g/d of curcumin failed to show any benefit on viral loads or CD4 count in HIV-positive individuals.

It was suggested that the poor bioavailability of curcumin could be a factor in these negative results.

Toxic and carcinogenic properties of curcumin The toxic and carcinogenic properties of an

extract of turmeric that is commonly added to food items and contains a high percentage of curcumin (79–85%) were evaluated in rats and mice by the National Toxicology Program, USA.

Toxic and carcinogenic effects were observed when animals were fed with the turmeric extract for a period of 2 years.

Conclusions Epidemiological studies suggest that

populations that live on a diet rich in curcumin have a lower cancer risk.

Accumulating preclinical studies have shown that curcumin can interfere with an increasing number of molecular targets, pathways and processes involved in cancer.

Thank You …..