Loureirin B protects against cerebral ischemia/reperfusion injury through modulating M1/M2 microglial polarization via STAT6 / NF-kappaB signaling pathway

Loureirin B 通过 STAT6 / NF-kappaB 信号通路调节 M1/M2 小胶质细胞极化,防止脑缺血/再灌注损伤

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作者:Rui Li, Huiyu Jia, Min Si, Xinwei Li, Zheng Ma, Yu Zhu, Wuyi Sun, Fengqin Zhu, Shengyong Luo

Abstract

The latest research indicates that modulating microglial polarization from M1 to M2 phenotype may be a coping therapy for ischemic stroke. The present study thereby evaluated the effects of loureirin B (LB), a monomer compound extracted from Sanguis Draconis flavones (SDF), on cerebral ischemic injury and the potential mechanisms. The middle cerebral artery occlusion (MCAO) model was established in male Sprague-Dawley rats to induce cerebral ischemia/reperfusion (I/R) injury in vivo, and BV2 cells were exposed to oxygen-glucose deprivation and reintroduction (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that LB significantly reduced infarct volume, neurological deficits and neurobehavioral deficits, apparently improved histopathological changes and neuronal loss in cortex and hippocampus of MCAO/R rats, markedly decreased the proportion of M1 microglia cells and the level of pro-inflammatory cytokines, and increased the proportion of M2 microglia and the level of anti-inflammatory cytokines both in vivo and in vitro. In addition, LB evidently improved the p-STAT6 expression and reduced the NF-κB (p-p65) expression after cerebral I/R injury in vivo and in vitro. IL-4 (a STAT6 agonist) exhibited a similar impact to that of LB, while AS1517499 (a STAT6 inhibitor) significantly reversed the effect of LB on BV-2 cells after OGD/R. These findings point to the protection of LB against cerebral I/R injury by modulating M1/M2 polarization of microglia via the STAT6/NF-κB signaling pathway, hence LB may be a viable treatment option for ischemic stroke.

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