Levistilide A reverses rat hepatic fibrosis by suppressing angiotensin II-induced hepatic stellate cells activation

The renin angiotensin system (RAS) serves an important role in the development of hepatic fibrosis. Therefore, the present study investigated the effect of levistilide A (Lev A) on hepatic fibrosis via regulation of RAS. The effects of Lev A on the proliferation and activation of hepatic stellate cells (HSCs) were measured using a 5-ethynyl-2′-deoxyuridine assay, western blot analysis and immunofluorescence. The in vivo anti-hepatic fibrosis effect of Lev A was examined using a CCL(4)-induced rat fibrosis model. Lev A significantly prohibited angiotensin (Ang) II-induced proliferation of HSCs, and overexpression of smooth muscle α-actin (α-SMA) and F-actin in HSCs. Lev A partly reversed Ang II-induced angiotensin type 1 receptor (AT1R) upregulation and ERK and c-Jun phosphorylation. In CCL(4)-induced hepatic fibrosis rats, Lev A treatment significantly decreased the expression of collagen, α-SMA and hydroxyproline in rat liver, and improved liver functions. Lev A treatment also significantly inhibited the CCL(4)-induced increase in plasma Ang II, and upregulation of AT1R and phosphorylated ERK in rat liver. In conclusion, Lev A is a potential agent for the treatment of hepatic fibrosis by suppressing Ang II/AT1R/ERK/c-Jun activation in HSCs.