Study On The Effect And Mechanism Of Swertiamarin On Hepatic Fibrosis Induced By Carbon Tetrachloride In Rats

Background & aims: Swertiamarin(STM)is a typical iridoid isolated from Swertia mussotii Franch(Gentianaceae)exerting broad pharmacological activities including hepatoprotective effect.STM was evaluated for anti-fibrotic effect and mechanism in rats with carbon tetrachloride-induced liver fibrosis in this study.Methods: Fifty adult male Sprague–Dawley rats were randomly divided into control group,STM 200mg/kg group,CCl4 group,CCl4+ STM 100mg/kg group and CCl4+STM 200mg/kg group.Rats in experimental groups were subcutaneously injected with 40% CCl4 twice weekly for eight weeks to develop liver fibrosis.STM(100 and 200 mg/kg per day)was orally given to experimental rats by gavage for eight consecutive weeks.The biomarkers in rat serum were determined with biochemical methods.The histopathology of the liver tissue was evaluated by use of hematoxylin-eosin(H&E)and Masson staining.The mRNA expressions of collagen I,collagen III and TGF-?1 in the liver were determined in the liver by real time PCR.The oxidative stress in liver tissue was evaluated.The levels of inflammatory cytokines/chemikines(IL-1?,IL-6,TNF-a,MIP-1a and MCP-1)were measured.The protein expression of CTGF,TLR4 and NF-?B was determined in the liver by Western blot analysis.Results: STM relieved CCl4 induced liver injury obviously.STM alsoameliorated histological changes and significantly suppressed collagen deposition in liver.RT-qPCR results revealed that collagen I,collagen III and TGF-?1 mRNA expression were decreased with STM treatment.STM significantly alleviated oxidative stress and reduced the levels of IL-1?,IL-6,TNF-a,MIP-1a and MCP-1 in the liver.Western blot assay showed CTGF,TLR4 and NF-?B expression was remarkably decreased after STM treatment.Conclusion: STM is able to attenuate CCl4 induced liver fibrosis in rat at least partly through its inhibition of oxidative stress and inflammation in liver.