Review
Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets

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Curcumin (diferuloylmethane), a yellow pigment in the spice turmeric (also called curry powder), has been used for centuries as a treatment for inflammatory diseases. Extensive research within the past two decades has shown that curcumin mediates its anti-inflammatory effects through the downregulation of inflammatory transcription factors (such as nuclear factor κB), enzymes (such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6). Because of the crucial role of inflammation in most chronic diseases, the potential of curcumin has been examined in neoplastic, neurological, cardiovascular, pulmonary and metabolic diseases. The pharmacodynamics and pharmacokinetics of curcumin have been examined in animals and in humans. Various pharmacological aspects of curcumin in vitro and in vivo are discussed in detail here.

Introduction

Traditional medicine is known to be fertile ground for the source of modern medicines [1]. One medicine in that category is curcumin, a yellow coloring agent present in the spice turmeric (Curcuma longa) that belongs to the ginger (Zingiberaceae) family. Besides its use in Indian cooking to add color and as a preservative, turmeric is used in Ayurveda (Indian traditional medicine) to treat various common ailments including stomach upset, flatulence, dysentery, ulcers, jaundice, arthritis, sprains, wounds, acnes, and skin and eye infections [2]. Curcumin was first isolated in 1815 by Vogel and Pelletier. Its chemical structure was determined in 1910 by J. Milobedzka and V. Lampe (Germany), its use in biliary diseases was documented in 1937 (67 patients treated), its antibacterial action in 1949 and its ability to decrease blood sugar levels in human subjects (i.e. its use as an antidiabetic) in 1972. Chemically, although curcumin is diferuloylmethane [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3, 5 dione], commercially available curcumin also contains ∼17% and 3% demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), respectively. Curcumin has been, however, shown to be more active than DMC or BDMC [3] (Figure 1). These studies indicate that bis-α,β-unsaturated β-diketone, two methoxy groups, two phenolic hydroxy groups and two double-conjugated bonds might play an essential part in the antiproliferative and anti-inflammatory activities assigned to curcumin. Various preclinical and clinical studies indicate that curcumin has potential therapeutic value against most chronic diseases including neoplastic, neurological, cardiovascular, pulmonary, metabolic and psychological diseases. How curcumin manifests these pharmacological effects in vitro and in vivo is discussed here.

Section snippets

Molecular targets

Our gain in knowledge about curcumin has been exponential over recent years. Since the first article on curcumin published in Nature in 1949, only 17 articles were published until 1980, 65 in the next 10 years, and 452 in the next 10. Since 2000, almost 2000 more publications have appeared in the National Institutes of Health PubMed database (www.ncbi.nlm.nih.gov/sites/entrez). These studies have revealed that curcumin has antioxidant, antibacterial, antifungal, antiviral, anti-inflammatory,

Pharmacological effects in animals

Numerous studies carried out in rodents show that curcumin is active in numerous animal models for chronic diseases (Figure 3). The anti-inflammatory, antiproliferative and antioxidant effects of curcumin described earlier indicate that curcumin is a highly pleiotropic molecule. This phytochemical has now been found to prevent neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases [29]. For instance, curcumin was found to correct cystic fibrosis through

Pharmacological effects in human

Almost 2500 preclinical studies in vitro and in vivo have prompted various clinical trials in human subjects. Almost 40 different clinical trials, mostly with small numbers of human subjects (∼25–50), have been completed 8, 63. Three different Phase I clinical trials performed to determine safety have indicated that curcumin given at doses as high as 15 g/day orally for 3 months is safe. No dose-limiting toxicity was reported.

The pharmacodynamics and pharmacokinetics of curcumin in humans was

Important limitations with curcumin

Although curcumin has been shown to modulate several targets that have been linked with cancer and various other chronic diseases, one of the most important limitations with curcumin is its bioavailability [74]. Whether performed in animals or human, studies have shown that when administered orally, curcumin is poorly bioavailable. Either no curcumin at all was found or only low levels of curcumin metabolites were detected in the serum or in the tissue. Curcumin seems to be metabolized through

Conclusion

Basic requirement for any chemopreventive agent demands that it should be non-toxic to normal and healthy people, have high efficacy against multiple sites, should be orally bioavailable, should have a known mechanism of action, should be easily available, should be low cost and should be acceptable to most of the human population. Curcumin meets several, if not all, of these requirements. The aforementioned description demonstrates that curcumin can modulate multiple cell-signaling pathways

Acknowledgements

We thank Walter Pagel for carefully proofreading the manuscript and providing valuable comments. We also thank Divya Danda for help with preparation of table. Owing to limitation of space, we would like to apologize to those whose important work could not be included. B.B.A. is the Ransom Horne Jr. Professor of Cancer Research. This work was supported by a grant from the Clayton Foundation for Research (to B.B.A).

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