The Mechanism of Astragaloside IV in NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome-mediated Pyroptosis after Intracerebral Hemorrhage.
Honggang Wu, Shu Chen, Guoliang You, Bo Lei, Li Chen, Jiachuan Wu, Niandong Zheng, Chao You
{"title":"The Mechanism of Astragaloside IV in NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome-mediated Pyroptosis after Intracerebral Hemorrhage.","authors":"Honggang Wu, Shu Chen, Guoliang You, Bo Lei, Li Chen, Jiachuan Wu, Niandong Zheng, Chao You","doi":"10.2174/0115672026295640240212095049","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke.</p><p><strong>Objectives: </strong>This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH.</p><p><strong>Methods: </strong>The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed. The levels of interleukin-1 beta (IL-1β), IL-18, tumor necrosis factor-alpha, interferon-gamma, and IL-10 were detected by enzyme-linked immunosorbent assay. The levels of Kruppel-like factor 2 (KLF2), NOD-like receptor family pyrin domain containing 3 (NLRP3), GSDMD-N, and cleaved-caspase-1 were detected by reverse transcription-quantitative polymerase chain reaction and Western blot assay. The binding relationship between KLF2 and NLRP3 was verified by chromatin-immunoprecipitation and dual-luciferase assays. KLF2 inhibition or NLRP3 overexpression was achieved in mice to observe pathological changes.</p><p><strong>Results: </strong>The decreased neurological function, increased water content, severe pathological damage, and inflammatory response were observed in mice after ICH, with increased levels of NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 and poorly-expressed KLF2 in brain tissue. After AS-IV treatment, the neurological dysfunction, high brain water content, inflammatory response, and pyroptosis were alleviated, while KLF2 expression was increased. KLF2 bonded to the NLRP3 promoter region and inhibited its transcription. Down-regulation of KLF2 or upregulation of NLRP3 reversed the effect of AS-IV on inhibiting pyroptosis and reducing inflammatory injury in mice after ICH.</p><p><strong>Conclusion: </strong>AS-IV inhibited NLRP3-mediated pyroptosis by promoting KLF2 expression and alleviated inflammatory injury in mice after ICH.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current neurovascular research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115672026295640240212095049","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke.
Objectives: This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH.
Methods: The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed. The levels of interleukin-1 beta (IL-1β), IL-18, tumor necrosis factor-alpha, interferon-gamma, and IL-10 were detected by enzyme-linked immunosorbent assay. The levels of Kruppel-like factor 2 (KLF2), NOD-like receptor family pyrin domain containing 3 (NLRP3), GSDMD-N, and cleaved-caspase-1 were detected by reverse transcription-quantitative polymerase chain reaction and Western blot assay. The binding relationship between KLF2 and NLRP3 was verified by chromatin-immunoprecipitation and dual-luciferase assays. KLF2 inhibition or NLRP3 overexpression was achieved in mice to observe pathological changes.
Results: The decreased neurological function, increased water content, severe pathological damage, and inflammatory response were observed in mice after ICH, with increased levels of NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 and poorly-expressed KLF2 in brain tissue. After AS-IV treatment, the neurological dysfunction, high brain water content, inflammatory response, and pyroptosis were alleviated, while KLF2 expression was increased. KLF2 bonded to the NLRP3 promoter region and inhibited its transcription. Down-regulation of KLF2 or upregulation of NLRP3 reversed the effect of AS-IV on inhibiting pyroptosis and reducing inflammatory injury in mice after ICH.
Conclusion: AS-IV inhibited NLRP3-mediated pyroptosis by promoting KLF2 expression and alleviated inflammatory injury in mice after ICH.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
