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| Description | |
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Curcuminoids are polyphenolic
pigments found in the spice turmeric. The term turmeric is used both for
the plant Curcuma longa L. and the spice derived from the rhizomes of the
plant. The major curcuminoids are curcumin, demethoxycurcumin and
bisdemethoxycurcumin. These substances comprise 3 to 6% of Curcuma longa.
Curcumin makes up 70 to 75% of the curcuminoids, demethoxycurcumin 15 to
20% and bisdemethoxycurcumin about 3%. Curcuma longa is a tropical plant native to south and southeast tropical Asia. It is a member of the ginger or Zingiberaceae family. Turmeric is widely consumed in the countries of origin for a variety of uses, including use as a dietary spice, as a dietary pigment and as an Indian folk medicine for the treatment of various illnesses. It is also used in Hindu religious ceremonies in one form or another as part of the religious rites. Curcuminoids are responsible for the yellow color of turmeric, as well as the yellow color of curry. Curcuminoids are derived from turmeric by extraction with ethanol. Curcumin is the most studied of the curcuminoids. In pure form, it is an orange-yellow, crystalline powder that is insoluble in water. It is also known as diferuloylmethane and turmeric yellow. Its chemical name is (E, E) -1, 7-bis(4-hydroxy-3- methoxyphenyl)-1,6-heptadiene-3, 5 dione. The molecular formula of curcumin is C21H20O6, its molecular weight is 368.39 daltons, and its structural formula is: urcumin and the other curcuminoids have been found to have antioxidant and anti-inflammatory activities and have been entered into Phase I clinical trials for cancer chemoprevention by the National Cancer Institute. ACTIONS AND PHARMACOLOGY ACTIONS Curcumin, demethoxycurcumin and bisdemethoxycurcumin have antioxidant activity. They may also have anticarcinogenic, anti-inflammatory, antiviral and hypocholesterolemic activities. MECHANISM OF ACTION The curcuminoids have been found to have a number of antioxidant activities, including scavenging of such reactive oxygen species as superoxide anions and hydrogen peroxide, inhibition of lipid peroxidation and inhibition of the oxidation of low-density lipoprotein (LDL). The reduced derivative of curcumin, tetrahydrocurcumin, has been found to have even stronger antioxidant activity. Tetrahydrocurcumin may be formed from curcumin following ingestion; however, this is unclear. The possible anticarcinogenic activity of curcumin and the other curcuminoids may be accounted for by a few mechanisms. These include inhibition of angiogenesis, upregulation of apoptosis, interference with certain signal transduction pathways that are critical for cell growth and proliferation, inhibition of colonic mucosa cyclooxygenase (COX) and lipoxygenase (LOX) activities and inhibition of farnesyl protein transferase. In addition to its possible activity in preventing malignant transformation and inhibiting tumor growth, curcumin may have antimetastatic potential, as well. In this regard, curcumin has been found to inhibit matrix metalloproteinase-9 in a human hepatocellular carcinoma cell line. The possible anticarcinogenic activity of the curcuminoids may be attributed, at least in part, to their ability to inhibit activation of the transcription factors NF-KappaB and AP-1. Curcuminoids have also been found to target the fibroblast growth factor-2 (FGF-2) angiogenic signaling pathway and inhibit expression of gelatinase B in the angiogenic process. In the final analysis, the curcuminoids' antioxidant activity may underlie many of the above mechanisms. Reactive oxygen species (ROS) can activate AP-1 and NF-KappaB. Further, FGF-2 induces AP-1 activation via ROS produced through NADPH oxidase. The curcuminoids, acting as antioxidants, may interfere with the ability of FGF-2 to stimulate AP-1, and they may generally inhibit the activation of NF-KappaB and AP-1. The possible anti-inflammatory activity of the curcuminoids may also be accounted for by several mechanisms, including inhibition of COX and LOX, reduction of the release of ROS by stimulated neutrophils, inhibition of AP-1 and NF-KappaB, and inhibition of the activation of the pro-inflammatory cytokines TNF (tumor necrosis factor) -alpha and IL (interleukin)-1 beta. Curcumin has modest anti HIV-1 activity. It has been found to inhibit HIV-1 and HIV-2 proteases, HIV-1 LTR (long terminal repeat)-directed gene expression, Tat-mediated transactivation of HIV-1-LTR and HIV-1 integrase. All of these actions have been demonstrated in vitro. There is no evidence that curcumin or the other curcuminoids significantly inhibit the replication of HIV-1 in vivo. The mechanism of the possible hypocholesterolemic effect of the curcuminoids is unclear. PHARMACOKINETICS The pharmacokinetics of the curcuminoids remain incompletely understood. Of the curcuminoids, curcumin has been most studied, mainly in animals. Curcumin is poorly absorbed following ingestion in mice and rats. In these animals, 38 to 75% of an ingested dose is excreted directly in the feces. Absorption appears to be better with food. In mice, the major metabolites of curcumin are curcumin glucuronoside, dihydrocurcumin glucuronoside, tetrahydrocurcumin glucuronoside and tetrahydrocurcumin. These metabolites are formed in the liver. Animal studies and the pharmacokinetics of curcumin are continuing. Human pharmacokinetic studies are needed. INDICATIONS AND USAGE The curcuminoids may have anticarcinogenic, anti-atherosclerotic, anti-inflammatory (including anti-arthritic), antiviral, antifungal and immune-modulating effects. They appear to help detoxify some drugs and other chemicals. There is some evidence the curcuminoids may help prevent cataracts and ameliorate chronic anterior uveitis. They may also help speed wound healing. Claims that the curcuminoids may be helpful in gall bladder disease are poorly supported. Credible clinical trials related to the curcuminoids in general are lacking. |
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