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Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of NAPDH oxidase 4.
MedLine Citation:
PMID:  23127783     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In our previous studies, we have reported that leonurine, a plant phenolic alkaloid in Herba leonuri, exerted cardioprotective properties in a number of preclinical experiments. Herein, we investigated the roles and the possible mechanisms of leonurine for reducing fibrotic responses in angiotensin II (Ang II)-stimulated primary neonatal rat cardiac fibroblasts and post-myocardial infarction (MI) rats. In vitro experiments were performed in neonatal rat cardiac fibroblasts, leonurine (10-20μM) pretreatment attenuated Ang II-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2), production of intracellular reactive oxygen species (ROS), expression and activity of matrix metalloproteinase (MMP)-2/9, as well as expression of α-smooth muscle actin (α-SMA) and types I and III collagen. A small interfering RNA-mediated knockdown strategy of NAPDH oxidase 4 (Nox4) revealed that Nox4 was required for Ang II-induced the activation of cardiac fibroblasts. In vivo studies using post-MI model in rats indicated that administration of leonurine inhibited myocardial fibrosis while reducing cardiac Nox4 expression, ROS production, NF-κB activation, and plasma MMP-2 activity. In conclusion, our results provided the first evidence that leonurine could prevent cardiac fibrosis and the activation of cardiac fibroblasts partly through modulation of Nox4-ROS pathway.
Authors:
Xin Hua Liu; Li Long Pan; Hai Yan Deng; Qing Hui Xiong; Dan Wu; Guo Ying Huang; Qi Hai Gong; Yi Zhun Zhu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-2
Journal Detail:
Title:  Free radical biology & medicine     Volume:  -     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
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