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contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth
1 Department of Pathology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA
2 Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA
3 Department of Pathology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA; Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center in Shreveport, Shreveport, LA, USA
* To whom correspondence should be addressed. E-mail: achen{at}lsuhsc.edu.
Hepatic fibrogenesis occurs as a wound-healing process after many forms of chronic liver injury. Hepatic fibrosis ultimately leads to cirrhosis if without effective treatments. Upon 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-gamma (PPAR
) inhibits the proliferation of non-adipocytes. 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 provided 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 anti-fibrotic candidate for prevention and treatment of hepatic fibrosis.
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