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

Autor: Ming-Xiang Zhang, Xiuhui Song, Er-shun Liang, Xue Liu, Zhanhui Du, Jianjun Lu, Yun Zhang, Xiaoqiong Liu, Yuxia Zhao, Xueying Chen
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Cardiac fibrosis
cardiac fibrosis
Smad Proteins
Traditional Chinese medicine
Pharmacology
p38 Mitogen-Activated Protein Kinases
Mice
0302 clinical medicine
Cell Movement
Heart Rate
Fibrosis
TGF-β1
Extracellular Signal-Regulated MAP Kinases
Traditional medicine
Cell Cycle
Cell Differentiation
Oncology
030220 oncology & carcinogenesis
diabetes mellitus
cardiovascular system
Collagen
Myofibroblast
Signal Transduction
Research Paper
medicine.drug
Cardiac function curve
Benzylisoquinolines
Diabetes Mellitus
Experimental

Transforming Growth Factor beta1
03 medical and health sciences
Diabetes mellitus
medicine
Animals
Cell Proliferation
Type 1 diabetes
business.industry
Myocardium
Fibroblasts
Streptozotocin
medicine.disease
Mice
Inbred C57BL

Diabetes Mellitus
Type 1

Glucose
030104 developmental biology
neferine
business
Drugs
Chinese Herbal
Zdroj: Oncotarget
ISSN: 1949-2553
DOI: 10.18632/oncotarget.11225
Popis: // Xue Liu 1, 2 , Xiuhui Song 3 , Jianjun Lu 4 , Xueying Chen 1 , Ershun Liang 1 , Xiaoqiong Liu 5 , Mingxiang Zhang 1 , Yun Zhang 1 , Zhanhui Du 1 , Yuxia Zhao 2 1 The 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 2 Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China 3 The People’s Hospital of Jimo City, Qingdao, Shandong 266200, China 4 The People’s Hospital of Qihe City, Dezhou, Shandong 251100, China 5 Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China Correspondence to: Zhanhui Du, email: duzhanhui@sdu.edu.cn Yuxia Zhao, email: yxzhao@sdu.edu.cn Keywords: neferine, diabetes mellitus, cardiac fibrosis, TGF-β1 Received: March 21, 2016 Accepted: July 27, 2016 Published: August 11, 2016 ABSTRACT 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.
Databáze: OpenAIRE