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Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells
Protein & Cell ; (12): 662-672, 2016.
Article in English | WPRIM | ID: wpr-757410
ABSTRACT
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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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pathology / Pharmacology / Phosphorylation / Quinolizines / Cell Line / Cyclin D1 / Dimethylnitrosamine / Alkaloids / Enzyme Activation / Proto-Oncogene Proteins c-akt Type of study: Prognostic study Limits: Animals Language: English Journal: Protein & Cell Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pathology / Pharmacology / Phosphorylation / Quinolizines / Cell Line / Cyclin D1 / Dimethylnitrosamine / Alkaloids / Enzyme Activation / Proto-Oncogene Proteins c-akt Type of study: Prognostic study Limits: Animals Language: English Journal: Protein & Cell Year: 2016 Type: Article