Curcumin regulates peroxisome proliferator-activated receptor-γ coactivator-1α expression by AMPK pathway in hepatic stellate cells in vitro

Curcumin exerts an inhibitory effect on hepatic stellate cell (HSC) activation, a key step for liver fibrogenesis, and on liver fibrosis by up-regulation of peroxisome proliferator-activated receptor-gamma (PPAR gamma) expression. PPAR gamma plays a crucial role in suppression of HSC activation. Peroxisome proliferator-activated receptor-gamma coactivator-la (PGC-1 alpha) functions as a co-activator for PPAR gamma. Therefore, researches on the effect of curcumin on PGC-1 alpha might contribute to understanding of the mechanisms underlying curcumin inhibition of HSC activation and liver fibrosis through PPAR gamma. The present study aimed to investigate the effect of curcumin on PGC-1 alpha expression in HSCs in vitro and examine the underlying molecular mechanisms by western blot, reat-time PCR, and transfection. Our results showed that curcumin stimulation increased PGC-1 alpha expression and the effects of curcumin on PGC-1 alpha expression were correlated with the activation of adenosine monophosphate-activated protein kinase (AMPK). Curcumin increased superoxide dimutase-2 (SOD2) transcription and activity by AMPK/PGC-1 alpha axis. Moreover. PGC-1 alpha was demonstrated to inhibit alpha 1(I) collagen (a marker for liver fibrosis) transcription in cultured HSCs. These results demonstrated the promotion effect of curcumin on PGC-1 alpha expression through AMPK pathway, which led to the increases in PPAR gamma activity and in SOD-2 transcription and activity. These data might suggest a possible new explanation for the inhibitory effect of curcumin on HSC activation and on liver fibrogenesis. (C) 2014 Elsevier B.V. All rights reserved.