6-shogaol alleviates excessive neuronal autophagy and calcium overload following cerebral ischemia-reperfusion injury by inhibiting the expression of DAPK1.
Ouyang Rao, Shixin Li, Ning Zhu, Hangxiang Zhou, Junling Tao, Yehong Li, Ying Liu
{"title":"6-shogaol alleviates excessive neuronal autophagy and calcium overload following cerebral ischemia-reperfusion injury by inhibiting the expression of DAPK1.","authors":"Ouyang Rao, Shixin Li, Ning Zhu, Hangxiang Zhou, Junling Tao, Yehong Li, Ying Liu","doi":"10.1016/j.neuroscience.2025.03.030","DOIUrl":null,"url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion injury (CIRI) is the primary pathological mechanism of ischemic stroke, leading to neuronal damage and triggering a series of pathological changes. This study investigates the neuroprotective effects and underlying mechanisms of 6-shogaol (6-SH) in CIRI. By establishing an in vitro OGD/R model and a rat cerebral ischemia-reperfusion model, we found that 6-SH significantly improved neuronal viability, alleviated pathological damage, and reduced autophagosome formation. Additionally, 6-SH treatment markedly inhibited the expression of DAPK1, decreased intracellular calcium ion concentration, and mitigated excessive autophagy. Mechanistic studies indicated that 6-SH reduces neuronal injury induced by CIRI by modulating DAPK1 phosphorylation and inhibiting its activity. This discovery provides a theoretical basis for considering 6-SH as a potential neuroprotective agent and offers new insights for clinical treatment of ischemic stroke.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":"74-84"},"PeriodicalIF":2.9000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.neuroscience.2025.03.030","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Cerebral ischemia-reperfusion injury (CIRI) is the primary pathological mechanism of ischemic stroke, leading to neuronal damage and triggering a series of pathological changes. This study investigates the neuroprotective effects and underlying mechanisms of 6-shogaol (6-SH) in CIRI. By establishing an in vitro OGD/R model and a rat cerebral ischemia-reperfusion model, we found that 6-SH significantly improved neuronal viability, alleviated pathological damage, and reduced autophagosome formation. Additionally, 6-SH treatment markedly inhibited the expression of DAPK1, decreased intracellular calcium ion concentration, and mitigated excessive autophagy. Mechanistic studies indicated that 6-SH reduces neuronal injury induced by CIRI by modulating DAPK1 phosphorylation and inhibiting its activity. This discovery provides a theoretical basis for considering 6-SH as a potential neuroprotective agent and offers new insights for clinical treatment of ischemic stroke.
期刊介绍：
Neuroscience publishes papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, will be considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
