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

Curcumin, a widely used spice and coloring agent in food, has been shown to possess potent antioxidant, antitumor promoting and anti-inflammatory prop erties in vitro and in vivo. The mechanism(s) of such pleiotropic action by this yellow pigment is unknown; whether induction of distinct antioxidant genes contributes to the beneficial activities mediated by curcumin remains to be investigated. In the present study we examined the effect of curcumi n on endothelial heme oxygenase-1 (HO-1 or HSP32), an inducible stress prot ein that degrades heme to the vasoactive molecule carbon monoxide and the a ntioxidant biliverdin. Exposure of bovine aortic endothelial cells to curcu min (5-15 mu M) resulted in both a concentration- and time-dependent increa se in HO-1 mRNA, protein expression and heme oxygenase activity. Hypoxia (1 8 h) also caused a significant (P < 0.05) increase in heme oxygenase activi ty which was markedly potentiated by the presence of low concentrations of curcumin (5 mu M). Interestingly, prolonged incubation (18 h) with curcumin in normoxic or hypoxic conditions resulted in enhanced cellular resistance to oxidative damage; this cytoprotective effect was considerably attenuate d by tin protoporphyrin IX, an inhibitor of heme oxygenase activity. In con trast, exposure of cells to curcumin for a period of time insufficient to u p-regulate HO-1 (1.5 h) did not prevent oxidant-mediated injury. These data indicate that curcumin is a potent inducer of HO-1 in vascular endothelial cells and that increased heme oxygenase activity is an important component in curcumin-mediated cytoprotection against oxidative stress. (C) 2000 Els evier Science Inc.