A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats
Joint Authors
Su, Changqing
Xu, Yang
Peng, Zhangxiao
Ji, Weidan
Li, Xiang
Lin, Xuejing
Qian, Liqiang
Li, Xiaoya
Chai, Xiaoyun
Wu, Qiuye
Gao, Quangen
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-06-18
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Xu, Yang& Peng, Zhangxiao& Ji, Weidan& Li, Xiang& Lin, Xuejing& Qian, Liqiang…[et al.]. 2015. A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats. BioMed Research International،Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1054620
Modern Language Association (MLA)
Xu, Yang…[et al.]. A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats. BioMed Research International No. 2015 (2015), pp.1-13.
https://search.emarefa.net/detail/BIM-1054620
American Medical Association (AMA)
Xu, Yang& Peng, Zhangxiao& Ji, Weidan& Li, Xiang& Lin, Xuejing& Qian, Liqiang…[et al.]. A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1054620
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1054620