MinireviewMultiple biological activities of curcumin: A short review
Introduction
Turmeric, Curcuma longa L. (Zingiberaceae family) rhizomes, has been widely used for centuries in indigenous medicine for the treatment of a variety of inflammatory conditions and other diseases (Ammon and Wahl, 1991). Its medicinal properties have been attributed mainly to the curcuminoids and the main component present in the rhizome includes curcumin (diferuloylmethane)—(1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-hepadiene-3,5-dione) (Fig. 1). Over the years, a number of studies have tried addressing the pharmacokinetics of curcumin that is poorly absorbed from intestine after oral administration of different doses of 3H-curcumin in rats (Ravindranath and Chandrasekhara, 1980, Ravindranath and Chandrasekhara, 1981, Ravindranath and Chandrasekhara, 1982). It was shown that oral consumption of curcumin in rats resulted in approximately 75% being excreted in the feces and only traces appeared in the urine (Wahlstrom and Blennow, 1978), whereas intra-peritoneal (i.p) administration accounted for similar levels of fecal excretion of curcumin, with only 11% found in bile (Holder et al., 1978) suggesting poor absorption of curcumin from the intestine. Numerous studies have suggested presence of different metabolites of curcumin. It has been shown to be bio-transformed to dihydrocurcumin and tetrahydrocurcumin. Subsequently, these products are converted to monoglucuronide conjugates (Pan et al., 1999). In another study, it was reported that the main biliary metabolites of curcumin are glucuronide conjugates of tetrahydrocurcumin (THC) and hexahydrocurcumin (Holder et al., 1978).
Curcumin has been shown to possess wide range of pharmacological activities including anti-inflammatory (Srimal and Dhawan, 1973, Satoskar et al., 1986), anti-cancer (Kuttan et al., 1985), anti-oxidant (Sharma, 1976, Toda et al., 1985), wound healing (Sidhu et al., 1998) and anti-microbial effects (Negi et al., 1999). Many of these biological effects of turmeric and its component curcumin, curcuminoids and curcumin oil are illustrated (Fig. 2). Recently, curcumin treatment has been shown to correct defects associated with cystic fibrosis in homozygous DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) knock out mice (Egan et al., 2004).
In vivo and in vitro studies have demonstrated curcumin's ability to inhibit carcinogenesis at three stages: tumor promotion, angiogenesis and tumor growth. Curcumin suppresses mitogen-induced proliferation of blood mononuclear cells, inhibits neutrophil activation and mixed lymphocyte reaction and also inhibits both serum-induced and platelet derived growth factor (PDGF)-dependent mitogenesis of smooth muscle cells (Huang et al., 1992). It has also been reported to be a partial inhibitor of protein kinase (Liu et al., 1993, Reddy and Aggarwal, 1994). The other salient feature of turmeric/curcumin is that despite being consumed daily for centuries in Asian countries, it has not been shown to cause any toxicity (Ammon and Wahl, 1991). Although a number of excellent reviews on curcumin are available, this short review specifically focuses on the anti-oxidant, wound healing, anti-angiogenic and anti-cancer effects of turmeric/curcumin.
Section snippets
Anti-oxidant activity
Oxidative stress plays a major role in the pathogenesis of various diseases including myocardial ischemia, cerebral ischemia–reperfusion injury, hemorrhage and shock, neuronal cell injury, hypoxia and cancer. Curcumin, exhibits strong antioxidant activity, comparable to vitamins C and E (Toda et al., 1985). Curcumin with its proven anti-inflammatory and anti-oxidant properties has been shown to have several therapeutic advantages. It was shown to be a potent scavenger of a variety of reactive
Curcumin enhances wound healing
Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Injury initiates a complex series of events that involves interactions of multiple cell types, various cytokines, growth factors, their mediators and the extra-cellular matrix proteins (ECM). Local application of turmeric is a household remedy in India for several conditions such as skin diseases, insect bites and chicken pox (Nadkarni, 1976). Based on the ancient use of turmeric
Modulation of angiogenesis by curcumin
Angiogenesis is the growth of new vascular capillary channels from preexisting vessels and is of fundamental importance in a number of physiological processes such as embryonic development, reproduction, wound healing and bone repair. On the other hand, uncontrolled angiogenesis is pathological and is often associated with tumor growth, rheumatoid arthritis, diabetic retinopathy and hemangiomas. Three decades of intensive research has strongly indicated involvement of angiogenesis in expansion
Anti-cancer effects of curcumin
Recent studies have found that curcumin has a dose-dependent chemopreventive effect in several animal tumor bioassay systems including colon, duodenal, stomach, esophageal and oral carcinogenesis. It has been shown to reduce tumors induced by benz(a) pyrene and 7, 12 dimethyl benz(a)anthracene (Singh et al., 1998, Deshpande et al., 1997, Azuine and Bhide, 1992), tumor promotion induced by phorbol esters (Huang et al., 1988) on mouse skin, on carcinogen-induced tumorigenesis in the fore stomach
Acknowledgments
The opinions or assertions contained herein are the private views of the authors and should not be construed as official or necessarily reflecting the views of the Uniformed Services University of the Health Sciences or the Department of Defense, USA. This work was supported by a grant (5 R21 AT000517-02) from the National Institute of Health, Bethesda and U.S.–India Foreign Currency fund from the U.S. State Department to USUHS.
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