Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature.

Curcumin, a yellow pigment present in the Indian spice turmeric (associated with curry powder), has been linked with suppression of inflammation; angiogenesis; tumorigenesis; diabetes; diseases of the cardiovascular, pulmonary, and neurological systems, of skin, and of liver; loss of bone and muscle; depression; chronic fatigue; and neuropathic pain. The utility of curcumin is limited by its color, lack of water solubility, and relatively low in vivo bioavailability. Because of the multiple therapeutic activities attributed to curcumin, however, there is an intense search for a "super curcumin" without these problems. Multiple approaches are being sought to overcome these limitations. These include discovery of natural curcumin analogues from turmeric; discovery of natural curcumin analogues made by Mother Nature; synthesis of "man-made" curcumin analogues; reformulation of curcumin with various oils and with inhibitors of metabolism (e.g., piperine); development of liposomal and nanoparticle formulations of curcumin; conjugation of curcumin prodrugs; and linking curcumin with polyethylene glycol. Curcumin is a homodimer of feruloylmethane containing a methoxy group and a hydroxyl group, a heptadiene with two Michael acceptors, and an alpha,beta-diketone. Structural homologues involving modification of all these groups are being considered. This review focuses on the status of all these approaches in generating a "super curcumin.".