Chlorogenic acid against carbon tetrachloride-induced liver fibrosis in rats.

This study examined the effects of chlorogenic acid (CGA) on liver fibrosis induced by carbon tetrachloride (CCl(4)) and explored the possible mechanisms of action. Liver fibrosis was induced in male Sprague-Dawley (SD) rats by the injection of 40% CCl(4) subcutaneously twice a week for eight weeks. At the same time, CGA (60 and 30mg/kg) was administered intragastrically once daily to a subset of rats. Upon pathological examination, the CGA-treated rats showed significantly reduced liver damage and symptoms of liver fibrosis. The expression of collagen I and collagen III mRNA was increased markedly by the CCl(4) treatment but this increase was suppressed by CGA. As compared with the CGA-treated group, the expression of bcl-2, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF-beta1) mRNA was increased in CCl(4) group, whereas Bax mRNA expression decreased. The expression of Bax and bcl-2 protein was confirmed by western blotting. Intragastric administration of CGA reduced the protein expression of alpha-smooth muscle actin (alpha-SMA) and glucose-regulated proteins 78 and 94 (GRP78 and GRP94) in rats injured by treatment with CCl(4). Our data indicate that CGA can efficiently inhibit CCl(4)-induced liver fibrosis in rats. Therefore, CGA could be an effective drug for preventing liver fibrosis.