Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of NADPH oxidase 4
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...
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Published in | Free radical biology & medicine Vol. 54; pp. 93 - 104 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.01.2013
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Subjects | |
Online Access | Get full text |
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Summary: | 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 (10–20μM) 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.
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► Leonurine inhibited Ang II-induced cardiac fibroblast activation. ► Nox4 siRNA abolished Ang II-induced fibrotic response, which was mimicked by leonurine. ► Inhibition of Nox4 expression by leonurine was involved in ERK signaling. ► Leonurine inhibited the Nox4–ROS system, accompanied by reduced myocardial fibrosis. |
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Bibliography: | http://dx.doi.org/10.1016/j.freeradbiomed.2012.10.555 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0891-5849 1873-4596 |
DOI: | 10.1016/j.freeradbiomed.2012.10.555 |