Acanthoic acid, a diterpene in Acanthopanax koreanum, ameliorates the development of liver fibrosis via LXRs signals

[Display omitted] •Acanthoic acid ameliorates liver fibrosis caused by CCl4in vivo.•Acanthoic acid modulates liver fibrosis via activation of LXRα and LXRβ.•Acanthoic acid inhibits HSCs activation via activation of LXRβ in vitro. Liver X receptors (LXRs)-mediated signals in acanthoic acid (AA) ameliorating liver fibrosis were examined in carbon tetrachloride (CCl4)-induced mice and TGF-β stimulated hepatic stellate cells (HSCs). AA was isolated from the root of Acanthopanax koreanum Nakai (Araliaceae). CCl4-treated mice were intraperitoneally injected with 10% CCl4 in olive oil (2mL/kg for 8weeks). In AA treated groups, mice were intragastrically administrated with AA (20mg/kg or 50mg/kg) 3 times per week for 8weeks. Administration of AA reduced serum aminotransferase and tissue necrosis factor-α (TNF-α) levels evoked by CCl4, and the reverse of liver damage was further confirmed by histopathological staining. Administration of AA reduced the expression of fibrosis markers and regulated the ratio of MMP-13/TIMP-1, further reversed the development of liver fibrosis. TGF-β (5ng/ml) was added to activate HSC-T6 cells for 2h, and then treated with AA (1, 3, or 10μmol/l) for 24h before analysis. Cells were collected and proteins were extracted to detect the expressions of LXRs. AA could inhibit the expression of α-SMA stimulated by TGF-β and increase the expression of LXRβ. In vivo and in vitro experiments, AA could modulate liver fibrosis induced by CCl4-treatment via activation of LXRα and LXRβ, while inhibit HSCs activation only via activation of LXRβ. Acanthoic acid might ameliorate liver fibrosis induced by CCl4 via LXRs signals.