Zhongfeng Xingnao Liquid Ameliorated the Early Impairment of Intracerebral Hemorrhage by Inhibiting NF-κB/NLRP3 Axis in Rats.

IF 4.2 2区 医学 Q2 IMMUNOLOGY
Journal of Inflammation Research Pub Date : 2025-07-03 eCollection Date: 2025-01-01 DOI:10.2147/JIR.S528358
Heyu Yang, Bingqian Luo, Yifan Du, Jiafu Guo, Shiqi Zhang, Ping Wang, Yuan Dai, Yun Lu, Shijun Xu
{"title":"Zhongfeng Xingnao Liquid Ameliorated the Early Impairment of Intracerebral Hemorrhage by Inhibiting NF-κB/NLRP3 Axis in Rats.","authors":"Heyu Yang, Bingqian Luo, Yifan Du, Jiafu Guo, Shiqi Zhang, Ping Wang, Yuan Dai, Yun Lu, Shijun Xu","doi":"10.2147/JIR.S528358","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Perihematomal neuroinflammation serves as a pivotal pathogenic driver of secondary brain injury during the acute stage of intracerebral hemorrhage (ICH). The traditional Chinese medicine Zhongfeng Xingnao Liquid exhibits anti-neuroinflammatory effects. This study aims to elucidate the optimal timing for ZFXN administration within hours of symptom onset and its underlying mechanisms, focusing on NF-κB/NLRP3-mediated neuroinflammation.</p><p><strong>Methods: </strong>ICH was induced by injection of autologous arterial blood into the left caudal nucleus. Neurological deficits scores, hematoma volume, cerebral blood flow (CBF), H&E and Nissl staining were conducted at 24 hours following ICH. The levels of neuroinflammation response and NF-κB/NLRP3 axis surrounding the hematoma were measured using immunofluorescent staining and Western blot. The inhibition of ZFXN on NF-κB/NLRP3 axis was further confirmed in Lipopolysaccharide (LPS)-induced BV-2 cells.</p><p><strong>Results: </strong>Post-ICH pathology was characterized by progressive hematoma expansion, elevated neurological deficit scores, neuronal damage, and reduced CBF, accompanied by neuroinflammatory. Early ZFXN intervention within 6 hours post-ICH significantly reduced hematoma volume and improved neurological scores (mNSS, Bederson, Zea Longa) at 24 hours, while markedly alleviating perihematomal neuronal damage and enhancing CBF, with optimal efficacy observed following one-hour administration. The treatment also effectively suppressed IL-1β/TNF-α release and microglial activation through NF-κB/NLRP3 pathway inhibition. Consistently, ZFXN diminished NF-κB-p65 nuclear translocation and downregulated NLRP3 inflammasome components (ASC, Cleaved Caspase-1) in LPS-stimulated BV-2 cells.</p><p><strong>Conclusion: </strong>ZFXN emerges as a promising neuroprotective agent for ICH through targeted inhibition of the NF-κB/NLRP3 inflammatory axis, demonstrating optimal efficacy within the critical 6-hour hyperacute phase by mitigating secondary neuroinflammation and addressing current therapeutic gaps in ICH management.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"8805-8819"},"PeriodicalIF":4.2000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234645/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inflammation Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/JIR.S528358","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Perihematomal neuroinflammation serves as a pivotal pathogenic driver of secondary brain injury during the acute stage of intracerebral hemorrhage (ICH). The traditional Chinese medicine Zhongfeng Xingnao Liquid exhibits anti-neuroinflammatory effects. This study aims to elucidate the optimal timing for ZFXN administration within hours of symptom onset and its underlying mechanisms, focusing on NF-κB/NLRP3-mediated neuroinflammation.

Methods: ICH was induced by injection of autologous arterial blood into the left caudal nucleus. Neurological deficits scores, hematoma volume, cerebral blood flow (CBF), H&E and Nissl staining were conducted at 24 hours following ICH. The levels of neuroinflammation response and NF-κB/NLRP3 axis surrounding the hematoma were measured using immunofluorescent staining and Western blot. The inhibition of ZFXN on NF-κB/NLRP3 axis was further confirmed in Lipopolysaccharide (LPS)-induced BV-2 cells.

Results: Post-ICH pathology was characterized by progressive hematoma expansion, elevated neurological deficit scores, neuronal damage, and reduced CBF, accompanied by neuroinflammatory. Early ZFXN intervention within 6 hours post-ICH significantly reduced hematoma volume and improved neurological scores (mNSS, Bederson, Zea Longa) at 24 hours, while markedly alleviating perihematomal neuronal damage and enhancing CBF, with optimal efficacy observed following one-hour administration. The treatment also effectively suppressed IL-1β/TNF-α release and microglial activation through NF-κB/NLRP3 pathway inhibition. Consistently, ZFXN diminished NF-κB-p65 nuclear translocation and downregulated NLRP3 inflammasome components (ASC, Cleaved Caspase-1) in LPS-stimulated BV-2 cells.

Conclusion: ZFXN emerges as a promising neuroprotective agent for ICH through targeted inhibition of the NF-κB/NLRP3 inflammatory axis, demonstrating optimal efficacy within the critical 6-hour hyperacute phase by mitigating secondary neuroinflammation and addressing current therapeutic gaps in ICH management.

中风醒脑液通过抑制NF-κB/NLRP3轴改善大鼠脑出血早期损伤。
背景:血肿周围神经炎症是脑出血(ICH)急性期继发性脑损伤的关键致病因素。中药中风醒脑液具有抗神经炎症作用。本研究旨在阐明ZFXN在症状出现数小时内给药的最佳时机及其潜在机制,重点关注NF-κB/ nlrp53介导的神经炎症。方法:采用自体动脉血注入左尾核诱导脑出血。脑出血后24小时进行神经功能缺损评分、血肿量、脑血流(CBF)、H&E和尼氏染色。采用免疫荧光染色和Western blot检测血肿周围神经炎症反应及NF-κB/NLRP3轴水平。在脂多糖(LPS)诱导的BV-2细胞中进一步证实了ZFXN对NF-κB/NLRP3轴的抑制作用。结果:脑出血后病理表现为进行性血肿扩张、神经功能缺损评分升高、神经元损伤、脑血流减少,并伴有神经炎症。脑出血后6小时内早期干预ZFXN可显著减少血肿体积,改善24小时神经系统评分(mNSS, Bederson, Zea Longa),同时显著减轻血肿周围神经元损伤,增强CBF,在给药1小时后疗效最佳。通过抑制NF-κB/NLRP3通路,有效抑制IL-1β/TNF-α释放和小胶质细胞活化。在lps刺激的BV-2细胞中,ZFXN一致地减少NF-κB-p65核易位,下调NLRP3炎症小体成分(ASC, Cleaved Caspase-1)。结论:ZFXN通过靶向抑制NF-κB/NLRP3炎症轴,成为一种有前景的脑出血神经保护剂,在关键的6小时超急性期表现出最佳疗效,减轻继发性神经炎症,解决目前脑出血治疗的治疗空白。
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 求助全文
来源期刊
Journal of Inflammation Research
Journal of Inflammation Research Immunology and Microbiology-Immunology
CiteScore
6.10
自引率
2.20%
发文量
658
审稿时长
16 weeks
期刊介绍: An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信