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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 7150376, 17 pages
https://doi.org/10.1155/2017/7150376
Research Article

Novel Therapeutic Effects of Leonurine On Ischemic Stroke: New Mechanisms of BBB Integrity

1Department of Pharmacology, School of Pharmacy and Institute of Biomedical Science, Fudan University, Shanghai, China
2Department of Pharmacology, School of Pharmacy, Macau University of Science & Technology, Macau

Correspondence should be addressed to Yi-Zhun Zhu; om.ude.tsum@uhzzy

Received 7 January 2017; Revised 10 April 2017; Accepted 16 April 2017; Published 13 June 2017

Academic Editor: Margherita Neri

Copyright © 2017 Qiu-Yan Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198), a compound extracted from Herba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO) rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB) breakdown. In the in vitro model of cell oxygen-glucose deprivation and reoxygenation (OGD/R), consistent results were obtained with decreased reactive oxygen species (ROS) production and maintained the BBB integrity. Further study demonstrated that SCM-198 increased the expression of histone deacetylase- (HDAC-) 4 which could inhibit NADPH oxidase- (NOX-) 4 and matrix metalloproteinase- (MMP-) 9 expression, resulting in the elevation of tight junction proteins, including claudin-5, occludin, and zonula occluden- (ZO-) 1. These results indicated SCM-198 protected BBB integrity by regulating the HDAC4/NOX4/MMP-9 tight junction pathway. Our findings provided novel insights into the protective effects and mechanisms of SCM-198 on ischemic stroke, indicating SCM-198 as a new class of potential drug against acute onset of ischemic stroke.