Effects of swertiamarin on TGF-β1/Smad signaling pathway in rats with carbon tetrachloride-induced liver fibrosis

Background & aims: Swertiamarin (SM) is a typical iridoid isolated from Swertia mussotii Franch (Gentianaceae) exerting broad pharmacological activities including hepatoprotective effect. SM was evaluated for anti-fibrotic effect and mechanism in rats with carbon tetrachloride-induced liver fibrosis in this study. Methods: Adult male Sprague-Dawley rats were randomly divided into control group, SM 200 mg/kg group, CCl4 group, CCl4+ SM 100 mg/kg group and CCl4+ SM 200 mg/kg group. Rats in experimental groups were subcutaneously injected with 40% CCl4 twice weekly for eight weeks to develop liver fibrosis. SM (100 and 200 mg/kg per day) was orally given to experimental rats by gavage for eight consecutive weeks. The histopathology of the liver tissue was evaluated by use of hematoxylin-eosin (H&E) staining. Immunohistochemical examination was carried out to detect the protein expressions of collagen I, collagen III and TGF-beta 1 in the liver, and the mRNA expressions of these genes were determined in the liver by real time PCR. The protein expression of p-Smad2 and p-Smad3 was determined in the liver by Western blot analysis. Results: SM ameliorated histological changes and significantly suppressed collagen deposition. Immunohistochemical staining revealed that collagen I, collagen III and TGF-beta 1 expression were decreased with SM treatment. SM significantly reduced the mRNA expression of collagen I, collagen III and TGF-beta 1 in the liver. Western blot assay showed p-Smad2 and p-Smad3 expression was significantly decreased after SM treatment. Conclusion: SM is able to attenuate CCl4 induced liver fibrosis in rat at least partly through its inhibition of TGF-beta 1/Smad signaling pathway.