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Dehydrocostus lactone (DHC) plays an anti\u2010inflammatory role in certain diseases. However, the role of DHC in neuroinflammation after ischemic stroke remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DHC was administered to lipopolysaccharide (LPS)\u2010treated BV2 cells and a middle cerebral artery occlusion (MCAO) model to detect the levels of inflammatory factors using quantitative real\u2010time PCR, western blotting, and behavioral tests. Morphological changes in microglia were observed using immunofluorescence. The Swiss Target Prediction database was used to predict the target of DHC. Finally, a specific inhibitor of the target protein was used to investigate its potential synergistic role in neuroinflammation, both with and without being combined with DHC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of inflammation\u2010related factors both in\u00a0vivo and in\u00a0vitro was improved by DHC, and the neurological deficits in mice after MCAO were improved in the DHC administration group. In addition, the Swiss Target Prediction showed that CYP2A6 was a target of DHC. Specifically, the combination of DHC with the CYP2A6 inhibitor showed that DHC exerts anti\u2010inflammatory effects in a CYP2A6\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Mechanistically, DHC inhibited neuroinflammation by binding to the target CYP2A6. Our study suggests that DHC is a promising new strategy for treating ischemic stroke.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70502","type":"journal-article","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T03:40:37Z","timestamp":1751686837000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dehydrocostus Lactone Inhibits Microglia\u2010Mediated Neuroinflammation by Targeting <scp>CYP2A6<\/scp> to Improve Ischemic Brain Injury"],"prefix":"10.1111","volume":"31","author":[{"given":"Xin","family":"Shu","sequence":"first","affiliation":[{"name":"Department of General Practice Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"},{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University  Nanjing 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