SCH 644343 alleviates ischemic stroke-induced neuroinflammation by promoting microglial polarization via the IL-4/SREBP-1 signaling pathway

Yufan Huang; Ke Li; Qijun Dai; Hanqing Pang; Ziyang Xu; Xin Luo; Liang Liu

doi:10.1016/j.ejphar.2023.176033

SCH 644343 alleviates ischemic stroke-induced neuroinflammation by promoting microglial polarization via the IL-4/SREBP-1 signaling pathway

Eur J Pharmacol. 2023 Nov 5:958:176033. doi: 10.1016/j.ejphar.2023.176033. Epub 2023 Sep 4.

Authors

Yufan Huang¹, Ke Li², Qijun Dai³, Hanqing Pang¹, Ziyang Xu⁴, Xin Luo¹, Liang Liu⁵

Affiliations

¹ Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225009, China.
² Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, China.
³ Department of Neurology, Haian Hospital of Traditional Chinese Medicine, Haian, 226600, China.
⁴ Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, 225009, China.
⁵ Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225009, China. Electronic address: liuliang@yzu.edu.cn.

PMID: 37673365
DOI: 10.1016/j.ejphar.2023.176033

Abstract

Ischemic stroke (IS), a kind of acute cerebrovascular disease, is one of the most common diseases, and it endangers the lives and health of elderly individuals. Inflammation is a key factor leading to stroke, making it a potential therapeutic target. Previous studies have found that neuroinflammation is closely associated with microglial polarization. Due to the various side effects of current drugs used to treat neuroinflammation, it is important to explore alternative drugs with anti-inflammatory activity for neuroinflammation treatment. In the present study, we investigated the effect of SCH 644343 (SCH), a natural compound, on neuroinflammation induced by IS and explored the mechanism. We found that SCH meliorated the phenotypes of IS in vivo, which was correlated with the increased percentage of infiltrated M2 macrophages in brain after stroke. SCH exerted a significant effect against oxygen-glucose deprivation/reoxygenation (OGD/R) in BV2 cells in vitro by inhibiting M1 microglial polarization and promoting M2 microglial polarization. Furthermore, suppression of SREBP-1 expression by pretreatment with the SREBP-1 inhibitor 25-HC attenuated the effect of SCH on IS in vitro. Taken together, SCH exerts anti-IS effect by promoting microglial polarization via the IL-4/SREBP-1 signaling pathway.

Keywords: IL-4/SREBP-1 signaling pathway; Ischemic stroke; Microglial polarization; Neuroinflammation; SCH 644343.