Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells
Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells作者机构：Department of Gastroenterology Shanghai General Hospital Nanjing Medical University Shanghai 200080 China
出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)
年 卷 期：2016年第7卷第9期
页 面：662-672页
核心收录：
学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 071010[理学-生物化学与分子生物学] 1002[医学-临床医学] 07[理学] 0703[理学-化学] 0836[工学-生物工程]
基 金：sponsored by the National Natural Science Foundation of China
主 题：matrine derivative hepatic stellate cellhepatic fibrosis epidermal growth factor receptor signaltransduction pathway
摘 要：Matrine （MT）, the effective component of Sophora fla- vescens Air, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells （HSCs） in both cell culture and animal models. Cytological experiments showed that MD-1 can inhibit the proliferation of HSC-T6 cells with a half-maximal inhibitory concentration （ICs0） of 62 pmollL. In addition, MD-1 more strongly inhibits the migration of HSC-T6 cells compared to MT and can more effectively induce G0/G1 arrest and apoptosis. Investigating the biological mechanisms underlying anti-hepatic fibrosis in the presence of MD-I, we found that MD-I can bind the epidermal growth factor receptor （EGFR） on the surface of HSC-T6 cells, which can further inhibit the phospho- rylaUon of EGFR and its downstream protein kinase B （Akt）, resulting in decreased expression of cyclin D1 and eventual inhibition of the activation of HSC-T6 cells. Furthermore, in rats with dimethylnitrosamine （DMN）- induced hepatic fibrosis, MD-1 slowed the development and progression of hepatic fibrosis, protecting hepatic parenchymal cells and improving hepatic functions. Therefore, MD-1 is a potential drug for anti-hepatic fibrosis.
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