Icariin protects against thioacetamide-induced liver fibrosis in rats: Implication of anti-angiogenic and anti-autophagic properties

Background: Liver fibrosis is a major health problem. The current study evaluated the potential of icariin (ICA) to guard against thioacetamide (TAA)-induced liver fibrosis in rats. Methods: Four groups of male rats were treated as follows: group 1 was the control group, group 2 was given TAA (200 mg/kg), group 3 was administered ICA (50 mg/kg) and TAA (200 mg/kg), and group 4 was given ICA (50 mg/kg) alone. Animal treatment was continued for four weeks.Results: Co-administration of ICA guarded against TAA hepatotoxicity as indicated by significant inhibition in the rise of serum ALT and AST activities and albumin concentrations. This was accompanied by inhibition of reduced glutathione depletion, superoxide dismutase exhaustion, and lipid peroxide accumulation. In addition, ICA inhibited the pathological alterations in liver architecture induced by TAA. The antifibrotic activity of ICA was verified by reduced hepatic collagen deposition in liver sections stained with Masson's trichrome and hepatic Col-1 alpha mRNA and hydroxyproline contents compared to the TAA-treated group. The antiangiogenic activity of ICA was evidenced by lowered levels of mRNA of Ang-1 and protein expression of VEGF, PDGF-beta, and CTGF immunohistochemically. Further, the anti-autophagic property of ICA was evidenced by amelioration of the decrease in mTOR and p70S6 kinase expression and an increase in TLR4, NF kappa B, ILl-beta, and COX-2 immunohistochemically. Moreover, ICA antagonized the increase in HMGB1, TGF-beta, and Beclin-1 and the decrease in BAMBI hepatic mRNA levels.Conclusions: ICA inhibits TAA-induced liver fibrosis in rats, possibly via inhibition of angiogenesis and autophagy. (C) 2017 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.