title: Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice.
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.
authors.affiliation: 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.|Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: The People's Hospital of Jimo City, Qingdao, Shandong 266200, China.
authors.forename: Xiuhui
authors.initials: X
authors.lastname: Song
authors.affiliation: The People's Hospital of Qihe City, Dezhou, Shandong 251100, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Xueying
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ershun
authors.initials: E
authors.lastname: Liang
authors.affiliation: Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Zhanhui
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D005947:Glucose / Q000737:chemistry; D006339:Heart Rate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C057222:neferine; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: TGF-β1; cardiac fibrosis; diabetes mellitus; neferine