A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats
Authors: Qiuye Wu
Liqiang Qian
Xiaoyun Chai
Zhangxiao Peng
Xiaoya Li
Weidan Ji
Yang Xu
Xuejing Lin
Changqing Su
Xiang Li
Quangen Gao
Journal: BioMed Research International (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hepatic stellate cells; Matrine; WM130; Antihepatic fibrosis; HSC-T6 cells
Affiliations: 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 Molecular Oncology, Eastern Hepatobiliary Surgery Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China ; Department of General Surgery, Wujiang No. 1 People's Hospital, Suzhou 215200, China., Department of General Surgery, Wujiang No. 1 People's Hospital, Suzhou 215200, China.

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. 

Retracted: No

PubPeer comments:
 Figure 3a may have a repeated image (green boxes). Could the authors please check? There appear to be 10 or so papers with shared authors and shared concerns. https: pubpeer.com search?q=authors%3A%22Changqing+Su%22 *** ![file] , 
 Thank you for your comment. You said that Figure 3a may have a repeated image (green boxes). We checked all data and Figures, we confirmed that, the two images seem to be the same, but they don t repeat. They are two pictures taken at different times within the same field of microscopic view. We attach these two original high-definition pictures. Please note that we have marked the places in the red circles in the pictures, so you can clearly distinguish these are completely different photos. Thank you again.![file] , 
 #2 Thank you for explaining and providing the higher resolution photos. I agree that these are not identical images. , 
 I agree with the authors. Dear Actinopolyspora Biskrensis, thank you for your tremendous time and energy to discover a large number of questionable articles, and for your positive contributions to the integrity of science. But this time, it is obvious that these two images are not reused, as too many details can prove this. Please do not blindly make judgments in order to catch a group of authors. I hope the editor of Pubpeer will make this passage public and not delete it. This is respect for the pubpeer platform and all readers. Thank you! , 
 #4 Thank you for your supportive comments. I certainly do not intend to cast doubt on a particular paper solely because of the authorship, however I sometimes look at collections of similar papers when a credible concern has already been raised. I agree with you that each paper should stand on its own and apologize for making an error in this case. I would note that the higher resolution image provided by the authors does make it easier to identify the differences than the image I originally accessed, which is why I worded my comment #1 as I did. ,