Research Papers:

This article has been corrected. Correction in: Oncotarget. 2022; 13:810-811.

Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice

Xue Liu, Xiuhui Song, Jianjun Lu, Xueying Chen, Ershun Liang, Xiaoqiong Liu, Mingxiang Zhang, Yun Zhang, Zhanhui Du _ and Yuxia Zhao

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Oncotarget. 2016; 7:61703-61715. https://doi.org/10.18632/oncotarget.11225

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Xue Liu1,2, Xiuhui Song3, Jianjun Lu4, Xueying Chen1, Ershun Liang1, Xiaoqiong Liu5, Mingxiang Zhang1, Yun Zhang1, Zhanhui Du1, Yuxia Zhao2

1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital , Shandong University, Jinan, Shandong 250012, China

2Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China

3The People’s Hospital of Jimo City, Qingdao, Shandong 266200, China

4The People’s Hospital of Qihe City, Dezhou, Shandong 251100, China

5Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China

Correspondence to:

Zhanhui Du, email: [email protected]

Yuxia Zhao, email: [email protected]

Keywords: neferine, diabetes mellitus, cardiac fibrosis, TGF-β1

Received: March 21, 2016    Accepted: July 27, 2016    Published: August 11, 2016


Cardiac fibrosis is a common pathological process accompanying diabetes mellitus. In this report, we studied the effects of neferine (a major bisbenzylisoquinline alkaloid derived from lotus embryos) on cardiac fibrosis induced by diabetes mellitus, as well as the underlying molecular pathways. In vivo, type 1 diabetes mellitus was induced in mice by administering streptozotocin. Diabetic mice were treated with neferine through oral gavage, and cardiac function was assessed using echocardiography. Total collagen deposition was assessed by Masson’s trichrome and Picrosirius staining. In vitro, cardiac fibroblasts were cultured in normal or high-glucose medium with or without neferine. Neferine attenuated left ventricular dysfunction and remodeling and reduced collagen deposition in diabetic mice. In vitro, neferine inhibited cardiac fibroblast proliferation, migration, and differentiation into myofibroblasts. In addition, neferine reduced high-glucose-induced collagen production and inhibited TGF-β1-Smad, ERK and p38 MAPK signaling activation in cardiac fibroblasts. These results suggest that neferine may have antifibrogenic effects in diabetes-related cardiac fibrosis.

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