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LIVER AND BILIARY TRACT

Activation of peroxisome proliferator-activated receptor- contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth

Departments of ¹Pathology and ²Cellular Biology and Anatomy, Louisiana State University Health Sciences Center in Shreveport, Shreveport, Louisiana 71130

Submitted 31 October 2002 ; accepted in final form 12 March 2003

Hepatic fibrogenesis occurs as a wound-healing process after many forms of chronic liver injury. Hepatic fibrosis ultimately leads to cirrhosis if not treated effectively. During liver injury, quiescent hepatic stellate cells (HSC), the most relevant cell type, become active and proliferative. Oxidative stress is a major and critical factor for HSC activation. Activation of peroxisome proliferator-activated receptor- (PPAR-) inhibits the proliferation of nonadipocytes. The level of PPAR- is dramatically diminished along with activation of HSC. Curcumin, the yellow pigment in curry, is a potent antioxidant. The aims of this study were to evaluate the effect of curcumin on HSC proliferation and to begin elucidating underlying mechanisms. It was hypothesized that curcumin might inhibit the proliferation of activated HSC by inducing PPAR- gene expression and reviving PPAR- activation. Our results indicated that curcumin significantly inhibited the proliferation of activated HSC and induced apoptosis in vitro. We demonstrated, for the first time, that curcumin dramatically induced the gene expression of PPAR- and activated PPAR- in activated HSC. Blocking its trans-activating activity by a PPAR- antagonist markedly abrogated the effects of curcumin on inhibition of cell proliferation. Our results provide a novel insight into mechanisms underlying the inhibition of activated HSC growth by curcumin. The characteristics of curcumin, including antioxidant potential, reduction of activated HSC growth, and no adverse health effects, make it a potential antifibrotic candidate for prevention and treatment of hepatic fibrosis.

apoptosis; antioxidants; fibrogenesis

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