Farnesoid X receptor activation is required for the anti-inflammatory and anti-oxidative stress effects of Alisol B 23-acetate in carbon tetrachloride-induced liver fibrosis in mice.

• 23ABA alleviated CCl 4 -induced liver injury and fibrosis in mice. • 23ABA suppressed the liver inflammation and oxidative stress in CCl 4 -treated mice. • FXR was essential for 23ABA-induced anti-liver injury and anti-fibrotic effects in CCl 4 -treated mice. • Inhibition of FXR attenuating the anti-oxidative stress and anti-inflammatory impacts of 23ABA in livers of CCl 4 -treated mice. • 23ABA was a promising compound for prevention or treatment of liver fibrosis. Previous studies have shown that Alisol B 23-acetate (23ABA) had potent liver-protection effects, however, its roles and potential mechanisms in carbon tetrachloride (CCl 4)-induced liver fibrosis remain to be determined. The present study aimed to investigate the effects of 23ABA on CCl 4 -induced liver fibrosis and tried to elucidate the underlying mechanisms by focusing on regulating of farnesoid X receptor (FXR). In vivo study found that 23ABA alleviated the CCl 4 -induced liver injury, and showed no obvious systemic toxicity on mice. 23ABA inhibited the collagen production, decreased sera levels of hyaluronic acid (HA) and procollagen type III (PC-III), lowered mRNA expression of α-smooth muscle actin (α-SMA), fibronectin, collagen I and collagen III in livers of mice. 23ABA inhibited the mRNA expressions and the sera levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α), as well as decreased the expression of cyclooxygenase 2 (COX-2) in fibrotic livers of mice. Besides, 23ABA decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased glutathione (GSH) level, enhanced activities of superoxide dismutase (SOD) and glutathione reductase (GR) as well as increased mRNA expression of nuclear factor-E2-related factor 2 (Nrf2), glutamate-cysteine ligase, catalytic subunit (GCLC) and glutamate-cysteine ligase, modifier subunit (GCLM). Further study showed that the anti-liver injury and anti-fibrotic effects of 23ABA were abrogated by FXR antagonist guggulsterone (GS) in vivo. In addition, the inhibition effects of 23ABA on liver inflammation and oxidative stress were also weakened by treatment with GS in CCl 4 -induced fibrotic mice livers. In conclusion, the protective effects of 23ABA against CCl 4 -induced liver injury and fibrosis, due to FXR-mediated regulation of liver inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]