Ligustroflavone ameliorates CCl-induced liver fibrosis through down-regulating the TGF-β/Smad signaling pathway.

Liver fibrosis is a pathological process characterized by excess deposition of extracellular matrix (ECM) that are mainly derived from activated hepatic stellate cells. Previous studies suggested that ligustroflavone (LF) was an ingredient of Ligustrum lucidum Ait. with activities of anti-inflammation and anti-oxidation. In this study, we investigated whether LF had any effect on liver fibrosis. In our study, we established a mouse model of carbon tetrachloride (CCl)-induced liver fibrosis and used TGF-β-stimulated human hepatic stellate cell line (LX-2) to explore the effect of LF and associated underlying mechanism. LF was used in vivo with low dose (L-LF, 5 mg·kg, i.p., 3 times each week) and high dose (H-LF, 20 mg·kg, i.p., 3 times each week) and in vitro (25 μmol·L). Histopathological and biochemical assays investigations showed that LF delayed the formation of liver fibrosis; decreased AST, ALT activities and increased Alb activity in serum; decreased MDA level, Hyp content and increased GSH-Px concentration, SOD activity in liver tissues. Moreover, immunohistochemical, immunofluorescent and Western blot results showed that LF reduced the expressions of hepatic stellate cells specific marker proteins, including collagen I and α-SMA in vivo and in vitro. In addition, LF markedly suppressed TGF-β-upregulated protein expressions of TβR I, TβR II, P-Smad2, P-Smad3 and Smad4 in LX-2 cells. Taken together, these findings demonstrated LF could decrease histopathological lesions, ameliorate oxidative injury, attenuate CCl-induced liver fibrosis, which may be associated with down-regulating the TGF-β/Smad signaling pathway.