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Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of NADPH oxidase 4.

Authors :
Liu XH
Pan LL
Deng HY
Xiong QH
Wu D
Huang GY
Gong QH
Zhu YZ
Source :
Free radical biology & medicine [Free Radic Biol Med] 2013 Jan; Vol. 54, pp. 93-104. Date of Electronic Publication: 2012 Nov 02.
Publication Year :
2013

Abstract

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 in vitro experiments performed in neonatal rat cardiac fibroblasts, leonurine (10-20 μM) pretreatment attenuated Ang II-induced activation of extracellular signal-regulated kinase 1/2, production of intracellular reactive oxygen species (ROS), expression and activity of matrix metalloproteinase (MMP)-2/9, and expression of α-smooth muscle actin and types I and III collagen. A small interfering RNA-mediated knockdown strategy for NADPH oxidase 4 (Nox4) revealed that Nox4 was required for Ang II-induced activation of cardiac fibroblasts. In vivo studies using a 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 provide the first evidence that leonurine could prevent cardiac fibrosis and the activation of cardiac fibroblasts partly through modulation of a Nox4-ROS pathway.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1873-4596
Volume :
54
Database :
MEDLINE
Journal :
Free radical biology & medicine
Publication Type :
Academic Journal
Accession number :
23127783
Full Text :
https://doi.org/10.1016/j.freeradbiomed.2012.10.555