Flavanones from Sedum sarmentosum Bunge Alleviate CCl(4)-Induced Liver Fibrosis in Rats by Targeting TGF-β1/TβR/Smad Pathway In Turn Inhibiting Epithelial Mesenchymal Transition

OBJECTIVE: The aim of the study is to evaluate the therapeutic effects of flavanones from Sedum sarmentosum Bunge (FSSB) on CCl(4)-induced liver fibrosis in rats and the underlying mechanisms of action. METHODS: An experimental model of liver fibrosis was established by subcutaneous injection of rats with CCl(4) (40% v/v, 3 ml/kg) twice per week for six weeks. FSSB (100, 200, and 400 mg/kg) was intragastrically administered once per day consecutively for five weeks. RESULTS: Our results showed that FSSB significantly attenuated CCl(4)-induced liver fibrosis as evidenced by reducing the elevated levels of serum biochemical indexes and improving the histological changes, including decreasing the elevation in serum alanine transaminase (ALT), aspartate transaminase (AST), hyaluronic acid (HA), and laminin (LN) level, reducing infiltration of inflammatory cells and collagen fibers in liver tissue. In addition, compared to the model group, FSSB markedly downregulated the protein and mRNA expression of TGF-β1, TGF-β1 receptors I and II (TβRI and TβRII), Smad2, Smad3, and Vimentin in liver tissue, at the mean time upregulating the expression of Smad7 and E-cadherin. CONCLUSIONS: The results suggest that FSSB alleviated CCl(4)-induced liver fibrosis probably through inhibition of TGF-β/TβR/Smad pathway in turn inhibiting epithelial mesenchymal transition.