Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice

Abstract

Context: Silymarin is the main flavonoid extracted from milk thistle, which has been used to treat liver diseases. Objective: The in vivo effect of silymarin on HFD-induced insulin resistance and fatty liver in mice was studied. Materials and methods: Male C57BL/6 mice were fed with high-fat diet (HFD) to induce obesity and insulin resistance and treated with 30, 60 mg/kg silymarin for 18 days. Food intake, body weight and the content/histology of epididymal fat and liver tissue were examined; the content of lipids, AST, ALT and inflammatory cytokines in serum were estimated. Results: Administration of silymarin caused bodyweight loss in diet induced obesity (DIO) mice (HFD group: 47.7 g, 60 mg/kg group: 43.0 g) while the food intake remain unchanged. Silymarin (60 mg/kg) significantly reduced the epididymal fat mass (from 1.75 g to 1.12 g). Elevated plasma lipids (TC 6.1 mM, TG 1.3 mM, LDL 1.2 mM) in DIO mice were all suppressed by silymarin (TC 4.5 mM, TG 0.89 mM, LDL 0.9 mM), as well as insulin (5.1 ng/ml in HFD group to 2.0 ng/ml (60 mg/kg silymarin). Examination of cytokine levels (TNF-α, IL-1β and IL-6) in each group proved that silymarin treatment significantly decreased inflammation in DIO mice. Finally, silymarin effectively protected liver from HFD-induced injury as evidenced by decreasing histological damage and reducing ALT and AST levels, as follows: ALT; 47.4 U/L in HFD group to 28.4 U/L (60 mg/kg silymarin); AST; 150.1 U/L in HFD group to 88.1 U/L (60 mg/kg silymarin) in serum. Discussion and conclusion: Our results suggested that silymarin-induced alleviation of inflammatory response could be a mechanism responsible for its benefits against liver damage and insulin resistance.