Hepatoprotective effect of Forsythiae Fructus water extract against carbon tetrachloride-induced liver fibrosis in mice

Abstract

Ethnopharmacological relevanceThe fruit of Forsythia suspensa (Thunb.) Vahl, named Forsythiae Fructus (Lian-Qiao), is a well-known traditional Chinese medicine (TCM) used for clearing away heat and toxic material, eliminating the mass and relieving swelling. Aim of the studyThis study aims to observe the attenuation of the water extract of Forsythiae Fructus (FSE) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in male C57BL/6 mice. Materials and methodsHepatic fibrosis was induced in male C57BL/6 mice by intraperitoneal injection with 2 ml/kg CCl4 (mixed 1: 3 in olive oil) twice a week for 4 weeks. At the same time, the mice were orally given with FSE (1, 2 g/kg) every day for 4 weeks. Serum biochemical parameters, gene and protein expression related to liver fibrosis were analyzed. The contents of forsythiaside A and forsythin in FSE were measured by high-performance liquid chromatography (HPLC). ResultsResults of serum alanine/aspartate aminotransferase (ALT/AST) activity and liver histological evaluation both showed the protection of FSE against CCl4-induced liver injury. Further, the anti-fibrotic effects of FSE was evidenced by the results of Masson's trichrome and Sirius red staining, liver hydroxyproline content, and serum amounts of hyaluronic acid, laminin, collagen Ⅳ and type III procollagen (PCIII). FSE also reduced the expression of α-smooth muscle actin (α-SMA) in livers from CCl4-injured mice. Additionally, FSE decreased the increased hepatic expression of fibroblast-specific protein 1 (FSP1) and vimentin induced by CCl4 in mice. ConclusionsFSE attenuates CCl4-induced liver fibrosis in mice by inhibiting hepatic stellate cells (HSCs) activation, reducing hepatic extracellular matrix (ECM) disposition and reversing epithelial-mesenchymal transition (EMT).