Effects of 18α-glycyrrhizin on TGF-β1/Smad signaling pathway in rats with carbon tetrachloride-induced liver fibrosis

Background: Glycyrrhizin has various pharmacological effects including hepato-protection. This study aimed to investigate the potential mechanism underlying the protective effects of 18 alpha-glycyrrhizin (18 alpha-GL) in rats with carbon tetrachloride (CCl4) induced liver fibrosis. Methods: Male Sprague-Dawley (SD) rats were randomly divided into control group, fibrosis group, 25 mg/kg 18 alpha-GL group and 12.5 mg/kg 18 alpha-GL group. Rats in experimental groups were subcutaneously injected with 40% CCl4 twice weekly for 8 weeks. Immunohistochemical examination was carried out to detect the protein expressions of collagen I, collagen III, TGF-beta 1, p-Smad2, p-Smad3, Smad 7 and SP-1, in the liver, and the mRNA and protein expressions of these genes were determined in the liver by real time PCR and Western blot assay, respectively. Results: 18 alpha-GL ameliorated histological changes and significantly suppressed collagen deposition. 18 alpha-GL significantly decreased the mRNA expressions of TGF-beta 1, Smad2, Smad3 and SP-1 in the liver. Immunohistochemical staining revealed that TGF-beta 1, p-Smad2, p-Smad3 and SP-1 expressions reduced following 18 alpha-GL therapy. Western blot assay showed p-Smad2, p-Smad3, smad2 and smad3 expressions decreased after 18 alpha-GL treatment. The mRNA and protein expression of Smad7 remained unchanged. Conclusion: 18 alpha-GL is able to attenuate CCl4 induced liver fibrosis in rat.