Elsevier

Life Sciences

Volume 78, Issue 18, 27 March 2006, Pages 2081-2087
Life Sciences

Minireview
Multiple biological activities of curcumin: A short review

https://doi.org/10.1016/j.lfs.2005.12.007Get rights and content

Abstract

Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented for its medicinal properties in Indian and Chinese systems of medicine. It has been widely used for the treatment of several diseases. Epidemiological observations, though inconclusive, are suggestive that turmeric consumption may reduce the risk of some form of cancers and render other protective biological effects in humans. These biological effects of turmeric have been attributed to its constituent curcumin that has been widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a result of extensive epidemiological, clinical, and animal studies several molecular mechanisms are emerging that elucidate multiple biological effects of curcumin. This review summarizes the most interesting in vitro and in vivo studies on the biological effects of curcumin.

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.

References (88)

  • R. Kuttan et al.

    Potential anticancer activity of turmeric (Curcuma longa)

    Cancer Letter

    (1985)
  • P. Manikandan et al.

    Curcumin modulates free radical quenching in myocardial ischaemia in rats

    International Journal of Biochemistry and Cell Biology

    (2004)
  • R. Mohan et al.

    Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth factor-2, including expression of matrix metalloproteinase gelatinase B

    Journal of Biological Chemistry

    (2000)
  • R. Motterlini et al.

    Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress

    Free Radical Biology and Medicine

    (2000)
  • C. Nirmala et al.

    Effect of curcumin on certain lysosomal hydrolases in isoproterenol-induced myocardial infarction in rats

    Biochemical Pharmacology

    (1996)
  • S. Park et al.

    Inhibition of fos–jun–DNA complex formation by dihydroguaiaretic acid and in vitro cytotoxic effects on cancer cells

    Cancer Letters

    (1998)
  • P. Rafiee et al.

    Cellular redistribution of inducible Hsp70 protein in the human and rabbit heart in response to the stress of chronic hypoxia: role of protein kinases

    Journal of Biological Chemistry

    (2003)
  • V. Ravindranath et al.

    Absorption and tissue distribution of curcumin in rats

    Toxicology

    (1980)
  • V. Ravindranath et al.

    In vitro studies on the intestinal absorption of curcumin in rats

    Toxicology

    (1981)
  • V. Ravindranath et al.

    Metabolism of curcumin-studies with [3H] curcumin

    Toxicology

    (1982)
  • S. Reddy et al.

    Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase

    FEBS Letters

    (1994)
  • T.P. Robinson et al.

    Design, synthesis, and biological evaluation of angiogenesis inhibitors: aromatic enone and dienone analogues of curcumin

    Bioorganic and Medicinal Chemistry Letters

    (2003)
  • A.J. Ruby et al.

    Anti-tumour and antioxidant activity of natural curcuminoids

    Cancer Letters

    (1995)
  • O.P. Sharma

    Antioxidant activity of curcumin and related compounds

    Biochemical Pharmacology

    (1976)
  • J.S. Shim et al.

    Hydrazinocurcumin, a novel synthetic curcumin derivative, is a potent inhibitor of endothelial cell proliferation

    Bioorganic and Medicinal Chemistry

    (2002)
  • Y. Shukla et al.

    Antimutagenic potential of curcumin on chromosomal aberrations in Wistar rats

    Mutation Research

    (2002)
  • A. Simon et al.

    Inhibitory effect of curcuminoids on MCF-7 cell proliferation and structure-activity relationships

    Cancer Letters

    (1998)
  • S. Singh et al.

    Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]

    Journal of Biological Chemistry

    (1995)
  • Y. Sugiyama et al.

    Involvement of the beta-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin

    Biochemical Pharmacology

    (1996)
  • S. Swarnakar et al.

    Curcumin regulates expression and activity of matrix metalloproteinases-9 and -2 during prevention and healing of indomethacin-induced gastric ulcer

    Journal of Biological Chemistry

    (2005)
  • M. Thiyagarajan et al.

    Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats

    Life Sciences

    (2004)
  • F. Yang et al.

    Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo

    Journal of Biological Chemistry

    (2005)
  • B.B. Aggarwal et al.

    Anticancer potential of curcumin: preclinical and clinical studies

    Anticancer Research

    (2003)
  • H.P. Ammon et al.

    Pharmacology of Curcuma longa

    Planta Medica

    (1991)
  • J.L. Arbiser et al.

    Curcumin is an in vivo inhibitor of angiogenesis

    Molecular Medicine

    (1998)
  • M.A. Azuine et al.

    Chemopreventive effect of turmeric against stomach and skin tumors induced by chemical carcinogens in Swiss mice

    Nutrition and Cancer

    (1992)
  • A. Bierhaus et al.

    The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B

    Thrombosis and Haemostasis

    (1997)
  • W.M. Boedefeld et al.

    Recent insights into angiogenesis, apoptosis, invasion, and metastasis in colorectal carcinoma

    Annals of Surgical Oncology

    (2003)
  • V. Calabrese et al.

    Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer's disease

    Italian Journal of Biochemistry

    (2003)
  • H.W. Chen et al.

    Effect of curcumin on cell cycle progression and apoptosis in vascular smooth muscle cells

    British Journal of Pharmacology

    (1998)
  • D. Deeb et al.

    Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells

    Molecular Cancer Therapeutics

    (2003)
  • M. Dikshit et al.

    Prevention of ischaemia-induced biochemical changes by curcumin and quinidine in the cat heart

    Indian Journal of Medical Research

    (1995)
  • T. Dorai et al.

    Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo

    Prostate

    (2001)
  • M.E. Egan et al.

    Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects

    Science

    (2004)
  • Cited by (0)

    View full text