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 CCL4‑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 CCL4‑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 CCL4‑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.