The Effect of Gypenosides on TGF-β1/Smad Pathway in Liver Fibrosis Induced by Carbon Tetrachloride in Rats

Objective: To investigate the effect of gypenosides on TGF‐β1/Smad pathway in liver fibrosis induced by carbon tetrachloride (CCl4) in rats. Method: Liver fibrosis in rats was induced by CCl4 subcutaneous injection over nine weeks, using 3 mg/kg of 100% CCl4 for the first injection and then 2 ml/kg of 50% CCl4‐olive oil solution, twice per week. At the beginning of the seventh week, the rats stimulated by CCl4 were divided into model group (n=12), gypenosides group (n=11) and colchicine group (n=11). The rats in the gypenosides and colchicine groups were administered with gypenosides (200 mg/kg.d) and colchicine (0.1mg/kg.d), respectively. The rest were administered with sterile water. At the end of the ninth week, hepatic hydroxyproline (Hyp) was tested and the histological changes in liver tissue were observed, as well as hepatic α‐smooth muscle actin (α‐SMA), transforming growth factor‐β1 (TGF‐β1), transforming growth factor‐β1 receptor (TβR‐I), transforming growth factor‐β2 receptor(TβR‐II), Smad2, phosphorylated Smad2 (p‐Smad2), Smad3 and phosphorylated Smad3 (p‐Smad3). Results: At the end of the experiment, two rats had died in the model group but none in the gypenosides and colchicine groups. With the stimulation of CCl4, hepatic Hyp content increased significantly in the model group but clearly decreased in the gypenosides and colchicine groups. Histological detection revealed serious steatosis, inflammation and fibrosis as well as collagen deposition in the liver tissue of the model group, but these were alleviated in the gypenosides and colchicine groups. The protein expressions of hepatic α‐SMA, TGF‐β1, TβR‐I, TβR‐II, Smad2, p‐Smad2 and p‐Smad3 were all up‐regulated in the model group. In the gypenosides‐treated group, the protein expressions of hepatic α‐SMA, TGF‐β1, Smad2, p‐ Smad2 and p‐Smad3 were all down‐regulated. In the colchicine‐treated group, hepatic α‐SMA, TGF‐β1, Smad2 and p‐Smad3 were also down‐regulated. The protein expressions of hepatic TβR‐I and TβR‐II were not inhibited significantly in the gypenosides‐ or colchicine‐ treated groups compared to the model group. 1 Lin Liu, Xue-mei Li, Liang Chen, Qin Feng, Lili Xu, Yi-yang Hu, Jing-hua Peng: The Effect of Gypenosides on TGF-s 1 /Smad Pathway in Liver Fibrosis Induced by Carbon Tetrachloride in Rats www.intechopen.com ARTICLE Int. j. integr. med., 2013, Vol. 1, 23:2013 Conclusion: Gypenosides alleviated liver fibrosis induced by CCl4 in rats, which is probably related to their inhibitory effects on hepatic stellate cell activation and the protein expression of TGF‐β1, Smad2, p‐Smad2 and p‐Smad3.