Chlorogenic acid protects against liver fibrosis in vivo and in vitro through inhibition of oxidative stress

Liver fibrosis is a scaring process related to chronic liver injury of all causes and as yet no truly effective treatment is available. Chlorogenic acid (CGA) is a phenolic compound and exerts anti-inflammatory and anti-oxidant activities. Our former studies suggested that CGA could prevent CCl4-induced liver fibrosis through inhibition of inflammatory signaling pathway in rats. However, whether the anti-oxidant activity is involved in the anti-fibrotic effect of CGA on liver fibrosis is not yet fully understood. This study examined whether CGA may prevent CCl4-induced liver fibrosis by improving anti-oxidant capacity via activation of Nrf2 pathway and suppressing the PDGF-induced profibrotic action via inhibition of NOX/ROS/MAPK pathway. The studies in vivo showed that the liver fibrosis degree, hydroxyproline content and expression of α-SMA, Collagen Ⅰ, Collagen Ⅲ and TIMP-1 were increased in CCl4-injected rats and which were alleviated markedly by CGA. Furthermore, CGA significantly decreased CYP2E1 expression and increased the expression of nuclear Nrf2 and Nrf2-regulated anti-oxidant genes (HO-1, GCLC and NQO1). CGA decreased MDA level and increased GSH, SOD and CAT levels in liver tissues. In vitro studies PDGF could induce NOX subunits (p47phox and gp91phox) expression, ROS production, p38 and ERK1/2 phosphorylation, HSCs proliferation and profibrotic genes expression in HSCs, all of which were reduced by CGA treatment. In conclusion, the results suggest that CGA protects against CCl4-induced liver fibrosis, at least in part, through the suppression of oxidative stress in liver and hepatic stellate cells.