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

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.

• Authors: Rui Li, Huiyu Jia, Min Si, Xinwei Li, Zheng Ma, Yu Zhu, Wuyi Sun, Fengqin Zhu, Shengyong Luo
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 953 Pg. 175860 (Aug 15 2023) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 37331681 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• NF-kappa B
• loureirin B
• Cytokines

Topics

• Rats
• Male
• Animals
• NF-kappa B (metabolism)
• Microglia
• Rats, Sprague-Dawley
• Signal Transduction
• Infarction, Middle Cerebral Artery (complications, drug therapy, metabolism)
• Brain Injuries (metabolism)
• Reperfusion Injury (drug therapy, prevention & control, metabolism)
• Ischemic Stroke (metabolism)
• Cytokines (metabolism)
• Brain Ischemia (metabolism)