Volume 7 Issue 9
Sep.  2016
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Yi Feng, Hai-yan Ying, Ying Qu, Xiao-bo Cai, Ming-yi Xu, Lun-gen Lu. Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells[J]. Protein&Cell, 2016, 7(9): 662-672. doi: 10.1007/s13238-016-0285-2
Citation: Yi Feng, Hai-yan Ying, Ying Qu, Xiao-bo Cai, Ming-yi Xu, Lun-gen Lu. Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells[J]. Protein&Cell, 2016, 7(9): 662-672. doi: 10.1007/s13238-016-0285-2

Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells

doi: 10.1007/s13238-016-0285-2
Funds:

This work was sponsored by the National Natural Science Foundation of China (Grant Nos. 81270518, 81500463, and 81470858).

  • Received Date: 2016-03-27
  • Rev Recd Date: 2016-05-24
  • Matrine (MT), the effective component of Sophora flavescens Ait, 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 (IC50) of 62 μmol/L. 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-1, we found that MD-1 can bind the epidermal growth factor receptor (EGFR) on the surface of HSC-T6 cells, which can further inhibit the phosphorylation 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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