Berberine Ameliorates Neuroinflammation by cGAS-STING-NLRP3 Axis in Cerebral Ischemia/Reperfusion Injury

Berberine Ameliorates Neuroinflammation by cGAS-STING-NLRP3 Axis in Cerebral Ischemia/Reperfusion Injury | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Berberine Ameliorates Neuroinflammation by cGAS-STING-NLRP3 Axis in Cerebral Ischemia/Reperfusion Injury Dan Wu, Tian Hu, Qi-Hong Lv, Han Xiao, Min-Zhen Deng, Ye-ling Ding, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8593386/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aims: This study aimed to investigate the protective mechanisms of berberine (BBR), the primary bioactive alkaloid of Coptidis rhizoma, against cerebral ischemia/reperfusion injury (CIRI), focusing on its integrated modulation of neuroinflammation and oxidative stress. Methods: A combination of in vivo and in vitro models was utilized. Neuroprotection was assessed in a rat model of transient middle cerebral artery occlusion (MCAO). Cytoprotective effects were further verified in SH-SY5Y neuroblastoma cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Molecular targets were identified through integrated analysis of in vivo and in vitro datasets. Results: BBR administration conferred significant neuroprotection in MCAO rats, evidenced by reduced cerebral infarct volume, improved neurological scores, enhanced antioxidant capacity (elevated GSH and SOD), and preserved mitochondrial integrity. In OGD/R-injured SH-SY5Y cells, BBR similarly increased GSH and SOD activity while decreasing levels of oxidized dsDNA, ROS, IL-1β, and TNF-α. Mechanistically, these benefits were attributed to the suppression of the cGAS/STING/NLRP3 signaling pathway. Notably, pharmacological inhibition of cGAS with RU.521 replicated the protective effects of BBR. Conclusion: These results demonstrate that BBR alleviates CIRI by attenuating neuroinflammation and oxidative stress via the cGAS‑STING‑NLRP3 axis, thereby identifying a novel mechanism and supporting the traditional use of Coptidis rhizome. Cerebral ischemia-reperfusion injury Berberine cGAS-STING Neuroinflammation Neuroprotection Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementarydata.docx WesternblotRAMDATA.pptx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8593386","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":580970285,"identity":"2c87c213-b357-4651-b6e9-c7c49e6b9069","order_by":0,"name":"Dan Wu","email":"","orcid":"","institution":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Dan","middleName":"","lastName":"Wu","suffix":""},{"id":580970286,"identity":"a0a82b79-6a72-4a98-b17c-65dd43eee70b","order_by":1,"name":"Tian Hu","email":"","orcid":"","institution":"The Second Affiliated Hospital of 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Injury","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cerebral ischemia-reperfusion injury, Berberine, cGAS-STING, Neuroinflammation, Neuroprotection","lastPublishedDoi":"10.21203/rs.3.rs-8593386/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8593386/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAims: This study aimed to investigate the protective mechanisms of berberine (BBR), the primary bioactive alkaloid of Coptidis rhizoma, against cerebral ischemia/reperfusion injury (CIRI), focusing on its integrated modulation of neuroinflammation and oxidative stress.\u003cbr\u003e\nMethods: A combination of in vivo and in vitro models was utilized. Neuroprotection was assessed in a rat model of transient middle cerebral artery occlusion (MCAO). Cytoprotective effects were further verified in SH-SY5Y neuroblastoma cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Molecular targets were identified through integrated analysis of in vivo and in vitro datasets.\u003cbr\u003e\nResults: BBR administration conferred significant neuroprotection in MCAO rats, evidenced by reduced cerebral infarct volume, improved neurological scores, enhanced antioxidant capacity (elevated GSH and SOD), and preserved mitochondrial integrity. In OGD/R-injured SH-SY5Y cells, BBR similarly increased GSH and SOD activity while decreasing levels of oxidized dsDNA, ROS, IL-1β, and TNF-α. Mechanistically, these benefits were attributed to the suppression of the cGAS/STING/NLRP3 signaling pathway. 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