Curcumin: A promise of native chemoprevention agent that need to be Fulfilled in clinical trials

Curcumin [diferuloylmethane (C₂₁H₂₀O₆)], a polyphenol, is an active principle of the perennial herb Curcuma longa (commonly known as turmeric) and found in turmeric, curry and mustard. It is a potent anti-oxidant and anti-inflammatory agent that is commonly consumed (as turmeric spice) at high quantities (up to 100mg/day) in certain eastern countries. Food-grade curcumin actually contains three similar compounds belonging to the curcuminoid family - curcumin, dimethoxycurcumin, and bisdimethoxycurcumin (approximately 69-77%, 17%, and 3-6%, respectively). It was traditionally used in eastern countries as folk medicine for various allergic and inflammatory respiratory conditions, as well as for liver disorders, anorexia, rheumatism, and wound healing. Extensive research over the last half century has revealed important functions of curcumin, such as anti-inflammatory, cytokines release, anti-oxidant, immunomodulatory, and anti-neoplastic properties. In vitro and in vivo studies have revealed the underlying mechanism of various curcumin activities. The anti-cancer effect of curcumin has been observed in a few clinical trials in colon and pancreatic cancer and in several high-risk premalignant conditions, where curcumin was used mainly as a native chemoprevention agent. Curcumin has also been shown to be a mediator of chemo-resistance and radio-resistance. It has been shown in vitro and in vivo that curcumin enhanced induction of apoptosis and potentiated the effect of known chemo-radiotherapies. Beside its use as an anti-cancerous agent, curcumin has been reported to have some beneficial effects in Alzheimer's disease and symptomatic relief of autoimmune diseases, such as psoriasis, ulcerative proctitis, uveitis and rheumatoid arthritis. Several clinical studies with healthy volunteers revealed a low bioavailability of curcumin, casting doubt on the efficacy of curcumin for medical conditions. Various methods to increase bioavailability of curcumin are currently assessed in the laboratory and in clinical trials. The possible clinical efficacy of this treatment as a chemopreventive or chemotherapeutic agent is yet to be proven. This review will range from a historical description to preclinical data, including mechanism(s) of action and existing clinical evidence, focusing on the potential of curcumin as chemopreventive agent.