Genistein-3'-sodium sulfonate Attenuates Neuroinflammation in Stroke Rats by Down-Regulating Microglial M1 Polarization through α7nAChR-NF-κB Signaling Pathway

• Published in: International journal of biological sciences Vol. 17; no. 4; pp. 1088 - 1100
• Main Authors: Liu, Chaoming, Liu, Song, Xiong, Lijiao, Zhang, Limei, Li, Xiao, Cao, Xingling, Xue, Jinhua, Li, Liangdong, Huang, Cheng, Huang, Zhihua
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 2021; Ivyspring International Publisher
• Subjects: alpha7 Nicotinic Acetylcholine Receptor - metabolism; Animals; Blood-brain barrier; Brain; Brain Infarction - prevention & control; Brain injury; Cell Line; Cerebral blood flow; Cytokines; Depolarization; Drug Evaluation, Preclinical; Estrogens; Experiments; Genistein; Genistein - analogs & derivatives; Genistein - pharmacology; Genistein - therapeutic use; Genotype & phenotype; Head injuries; IL-1β; Inflammation; Injury prevention; Ischemia; Ischemic Stroke - drug therapy; Ischemic Stroke - metabolism; Laboratories; Lipopolysaccharides; Male; Mice; Microglia; Microglia - drug effects; Microglial cells; Neuroinflammatory Diseases - prevention & control; Neuroprotection; NF-kappa B - metabolism; NF-κB protein; Occlusion; Penicillin; Phosphorylation; Rats; Rats, Sprague-Dawley; Reperfusion; Research Paper; Signal transduction; Signal Transduction - drug effects; Signaling; Sodium; Stroke; Sulfonates; Traumatic brain injury; Tumor necrosis factor-TNF; Veins & arteries; United Kingdom > UK; United States > US; Massachusetts; China; Neuroinflammation; Ischemic stroke; Genistein-3′-sodium sulfonate; α7nAChR-NF-κB signaling; Microglia polarization
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.56800

Microglial M1 depolarization mediated prolonged inflammation contributing to brain injury in ischemic stroke. Our previous study revealed that Genistein-3'-sodium sulfonate (GSS) exerted neuroprotective effects in ischemic stroke. This study aimed to explore whether GSS protected against brain injury in ischemic stroke by regulating microglial M1 depolarization and its underlying mechanisms. We established transient middle cerebral artery occlusion and reperfusion (tMCAO) model in rats and used lipopolysaccharide (LPS)-stimulated BV2 microglial cells as
model. Our results showed that GSS treatment significantly reduced the brain infarcted volume and improved the neurological function in tMCAO rats. Meanwhile, GSS treatment also dramatically reduced microglia M1 depolarization and IL-1β level, reversed α7nAChR expression, and inhibited the activation of NF-κB signaling in the ischemic penumbra brain regions. These effects of GSS were further verified in LPS-induced M1 depolarization of BV2 cells. Furthermore, pretreatment of α7nAChR inhibitor (α-BTX) significantly restrained the neuroprotective effect of GSS treatment in tMCAO rats. α-BTX also blunted the regulating effects of GSS on neuroinflammation, M1 depolarization and NF-κB signaling activation. This study demonstrates that GSS protects against brain injury in ischemic stroke by reducing microglia M1 depolarization to suppress neuroinflammation in peri-infarcted brain regions through upregulating α7nAChR and thereby inhibition of NF-κB signaling. Our findings uncover a potential molecular mechanism for GSS treatment in ischemic stroke.