Cedrol attenuates acute ischemic injury through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways

IF 3.5 3区 医学 Q2 NEUROSCIENCES Brain Research Bulletin Pub Date : 2024-10-15 DOI:10.1016/j.brainresbull.2024.111102
Yu Bi , Ziyi Xie , Xiang Cao , Huanyu Ni , Shengnan Xia , Xinyu Bao , Qinyue Huang , Yun Xu , Qingxiu Zhang
{"title":"Cedrol attenuates acute ischemic injury through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways","authors":"Yu Bi ,&nbsp;Ziyi Xie ,&nbsp;Xiang Cao ,&nbsp;Huanyu Ni ,&nbsp;Shengnan Xia ,&nbsp;Xinyu Bao ,&nbsp;Qinyue Huang ,&nbsp;Yun Xu ,&nbsp;Qingxiu Zhang","doi":"10.1016/j.brainresbull.2024.111102","DOIUrl":null,"url":null,"abstract":"<div><div>Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"218 ","pages":"Article 111102"},"PeriodicalIF":3.5000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Research Bulletin","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0361923024002363","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

Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
西地孕酮通过ERβ-NF-κB信号通路抑制与小胶质细胞相关的神经炎症,从而减轻急性缺血性损伤。
小胶质细胞相关神经炎症在急性中风的病理过程中起着至关重要的作用。从生姜中提取的天然化合物 Cedrol 已被证明对多种疾病的炎症具有抑制作用。然而,Cedrol 是否能抑制神经炎症并保护大脑免受急性缺血性损伤仍不清楚。在这项研究中,我们发现 Cedrol 可抑制 LPS 挑战的小胶质细胞和大脑中动脉闭塞(MCAO)小鼠半影区的小胶质细胞活化和炎症因子的产生。我们还发现,Cedrol能缩小脑梗塞面积,降低mNSS评分,改善急性脑缺血诱发的行为结果,这表明Cedrol具有显著的神经保护作用。分子对接分析表明,Cedrol与雌激素受体β(ERβ)结合的亲和力中等偏上。耐人寻味的是,用雌激素受体阻断剂氟维司群处理后,Cedrol的抗炎作用消失了。Cedrol能明显逆转LPS和MCAO分别诱导的原代小胶质细胞和MCAO小鼠IκB和NF-κB P65磷酸化水平的升高。此外,在原代小胶质细胞中,观察到 Cedrol 可挽救 LPS 诱导的 NF-κB P65 从细胞质到细胞核的穿梭,这表明 Cedrol 对 NF-κB 信号传导有抑制作用。这些结果表明,与小胶质细胞相关的神经炎症可能是由 ERβ-NF-κB 信号通路介导的。总之,我们的研究揭示了赛德罗通过ERβ-NF-κB信号通路抑制小胶质细胞相关神经炎症,从而保护急性脑缺血的脑功能,赛德罗可作为治疗急性中风损伤的替代选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Brain Research Bulletin
Brain Research Bulletin 医学-神经科学
CiteScore
6.90
自引率
2.60%
发文量
253
审稿时长
67 days
期刊介绍: The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.
期刊最新文献
Neurobiological correlates of reactive aggression in young adults with internet gaming disorder Resveratrol alleviates depression-like behaviors by inhibiting ferroptosis via AKT/NRF2 pathway Amyloid Beta-Induced Mitochondrial Dysfunction and Endothelial Permeability in Cerebral Microvascular Endothelial cells: the protective role of Dexmedetomidine. Vibrotactile stimulation at 40 Hz inhibits Aβ-induced changes in SH-SY5Y, BV2 cells, and pericytes Activation of MSK-1 exacerbates neuropathic pain through histone H3 phosphorylation in the rats’ dorsal root ganglia and spinal dorsal horn
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1