Effects of artesunate and ceramide on cell proliferation,collagen generated and MMP13 expression in hepatic stellate cells

Objective: To investigate the impact of artesunate and ceramide on cell proliferation and collagen generated,and to analyze the underlying molecular mechanisms of anti-fibrogenic effects involving matrix metalloprotenase 13(MMP13) expression in hepatic stellate cells(HSCs).Methods: Isolated,cultured,and activated,HSCs were divided into seven groups,including one control group,five artesunate-treated experimental groups with 125,150,175,200 or 225 μmol/L and one ceramide-treated experimental group with 10 μmol/L for 24,48 or 72 hours.The rate of cellular proliferation was measured using the 3-(4,5-dime-thylthiazol-2-yl)-2,5-diphenylterazolium bromide(MTT) assay,and the determination of hydroxyproline(Hyp) was acquired by the enzyme digestion method.MMP13 expression was evaluated by Western blotting.Results: The absorbance value in artesunate and ceramide group reduced significantly compared with that in the control group at different points(P0.01).As the concentration increasing and time forwarding,the inhibition of proliferation ehanced;Artesunate in different doses and ceramide could effectively reduce the content of Hyp(P0.01),and had a dose-effect relationship;Artesunate in different doses and ceramide could promote MMP13 expression(P0.01),and also presented a dose-effect relationship.Conclusion: Artesunate and ceramide have anti-hepatic fibrosis effect.The possible mechanism may be that they can inhibit the proliferation of HSCs,reduce the secretion of collagen,improve the expression of MMP13 in order to promote degradation of collagen and decrease extracellular matrix.