Quercetin alleviates cerebral ischemia and reperfusion injury in hyperglycemic animals by reducing endoplasmic reticulum stress through activating SIRT1

作者：Jing Yang, Yanmei Ma, Lan Yang, Peng Li, Jing Li, P. Andy Li, P. Andy Li, P. Andy Li, Jianzhong Zhang · 发表于：PLoS ONE · 年份：2025 · DOI：10.1371/journal.pone.0321006 · 被引用次数：10 · 研究领域：Endoplasmic Reticulum Stress and Disease、Autophagy in Disease and Therapy、Sirtuins and Resveratrol in Medicine

Hyperglycemia aggravates cerebral ischemic reperfusion injury (CIRI). Neuroprotective drugs that are effective in reducing CIRI in animals with normoglycemic condition are ineffective in ameliorating CIRI under hyperglycemic condition. This study investigated whether quercetin alleviates hyperglycemic CIRI by inhibiting endoplasmic reticulum stress (ERS) through modulating the SIRT1 signaling pathway. A middle cerebral artery occlusion/reperfusion (MCAO/R) model was induced in STZ-injected hyperglycemic rats. High glucose and oxygen glucose deprivation/reoxygenation (OGD/R) models were established in HT22 cells. The results demonstrated that hyperglycemia exacerbated CIRI, and quercetin pretreatment decreased the neurological deficit score and cerebral infarct volume, and alleviated neuron damage in the cortex of the penumbra in hyperglycemic MCAO/R rats, indicating that quercetin could be a candidate for treating hyperglycemic CIRI. Moreover, quercetin pretreatment reduced apoptosis, inhibited the expression of the ERS marker proteins GRP78 and ATF6, and mitigated the expression of the ERS-mediated proapoptotic protein CHOP in hyperglycemic MCAO/R rats, suggesting that quercetin alleviated hyperglycemic CIRI by inhibiting ERS and ERS-mediated apoptosis. Furthermore, quercetin upregulated Sirt1 expression in HG+OGD/R treated HT22 cells and inhibited PERK, p-eIF2α, ATF4, and CHOP expression. In contrast, the SIRT1 selective inhibitor EX-527 blocked the effect of quercetin on p...