A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in RatsReportar como inadecuado




A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BioMed Research International - Volume 2015 2015, Article ID 203978, 13 pages -

Research Article

Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China

Deparment of Pharmacy, Second Military Medical University, Shanghai 200433, China

Department of General Surgery, Wujiang No. 1 People’s Hospital, Suzhou 215200, China

Received 12 February 2015; Revised 21 May 2015; Accepted 2 June 2015

Academic Editor: Kusum Kharbanda

Copyright © 2015 Yang Xu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Activation of hepatic stellate cells HSCs is a critical event in process of hepatic fibrogenesis and cirrhosis. Matrine, the active ingredient of Sophora, had been used for clinical treatment of acute-chronic liver disease. However, its potency was low. We prepared a high potency and low toxicity matrine derivate, WM130 C30N4H40SO5F, which exhibited better pharmacological activities on antihepatic fibrosis. This study demonstrated that WM130 results in a decreased proliferative activity of HSC-T6 cells, with the half inhibitory concentration IC50 of 68 μM. WM130 can inhibit the migration and induce apoptosis in HSC-T6 cells at both concentrations of 68 μM IC50 and 34 μM half IC50. The expression of α-SMA, Collagen I, Collagen III, and TGF-β1 could be downregulated, and the protein phosphorylation levels of EGFR, AKT, ERK, Smad, and Raf p-EGFR, p-AKT, p-ERK, p-Smad, and p-Raf were also decreased by WM130. On the DMN-induced rat liver fibrosis model, WM130 can effectively reduce the TGF-β1, AKT, α-SMA, and p-ERK levels, decrease the extracellular matrix ECM formation, and inhibit rat liver fibrosis progression. In conclusion, this study demonstrated that WM130 can significantly inhibit the activation of HSC-T6 cells and block the rat liver fibrosis progression by inducing apoptosis, suppressing the deposition of ECM, and inhibiting TGF-β-Smad and Ras-ERK pathways.





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Fuente: https://www.hindawi.com/



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