The Molecular Mechanism of Quercetin Improving Cerebral Ischemia Injury by Regulating NLRP3 Inflammasome Mediated Pyroptosis Axis

Background In the pathological process of cerebral ischemia, the neuroinflammation triggered by NLRP3 inflammasome-mediated neuronal pyroptosis is considered a crucial factor contributing to brain damage. Although, previous research has revealed the anti-inflammatory and neuroprotective effects of quercetin (Que), its precise mechanisms in intervening and alleviating neuroinflammation and the pyroptosis axis triggered by cerebral ischemia remain to be fully elucidated. Objective To investigate the role and mechanism of Que in alleviating cerebral ischemia injury by modulating the NLRP3 inflammasome-mediated pyroptosis axis. Methods The oxygen-glucose deprivation and reperfusion (OGD/R) model with BV2 microglial cells and the photothrombosis (PT) model with C57/BL male mice were utilized. The study explored the neuroprotective effect of Que against cerebral ischemia injury through the regulation of the pyroptosis axis via the NLRP3 inflammasome, assessed through experiments including reactive oxygen species measurement, cell pyroptosis rate detection, behavioral tests, HE staining, Nissl staining, and examination of pyroptosis-related proteins and inflammatory factors. Results Que alleviated cell damage and pyroptosis induced by OGD/R, reduced intracellular reactive oxygen species levels, improved behavioral impairment in mice after modeling, decreased brain injury area, maintained neuronal morphology, and lowered the expression of pyroptosis axis-related proteins such as NLRP3, Caspase-1, ASC, GSDMD, as well as inflammatory factors IL-18, IL-1β, TNF-α. Conclusion Que alleviated cerebral ischemia injury by regulating the pyroptosis axis through inhibiting the activation of NLRP3 inflammasome. This provides robust experimental evidence for the anti-neuroinflammatory effects of Que and the development of neuroprotective drugs.