{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:08:40Z","timestamp":1789168120212,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The crosstalk between ferroptosis and neuroinflammation plays an important role in the pathogenesis of cerebral ischemia\u2013reperfusion injury. Toosendanin (TSN), a triterpenoid compound, exhibits a wide range of pharmacological activities in human diseases. Here we investigated the potential neuroprotective effects of TSN in cerebral ischemia\u2013reperfusion injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In our study, in\u00a0vivo murine middle cerebral artery occlusion (MCAO) model and in\u00a0vitro oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) model were constructed to mimic cerebral ischemia\u2013reperfusion injury. TTC staining, open\u2010field test, Morris water maze test, hanging wire test, rotarod test, foot\u2010fault test, hematoxylin and eosin (H&amp;E) staining, flow cytometry, western blot and reverse transcription\u2010quantitative PCR were conducted to evaluate the potential influence of TSN in cerebral ischemia\u2013reperfusion injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results indicated that post\u2010stroke administration of TSN significantly reduced infarct volume and improved long\u2010term functional recovery of MCAO mice. Mechanistically, TSN alleviated neural oxidative stress, lipid peroxidation, and ferroptosis in MCAO mice or in\u00a0vitro after OGD\/R. In addition, TSN modulated the infiltrating of immune cells in MCAO mice in\u00a0vivo and T cell differentiation in\u00a0vitro. Mechanistically, TSN directly interacted with ACSL4 and suppressed its enzymatic activity, thus suppressing the ACSL4\/LPCAT3 axis to reduce the incorporation of pro\u2010ferroptotic polyunsaturated fatty acids (PUFA) into phospholipids, and finally inhibiting lipid peroxidation and neural ferroptosis. In addition, the induction of ferroptosis abrogated the influence of TSN on immune infiltration and lipid metabolism in MCAO mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings identify TSN as a promising therapeutic agent for cerebral ischemia\u2013reperfusion injury via inhibiting ACSL4\u2010mediated ferroptosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70952","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T06:19:53Z","timestamp":1780121993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Toosendanin Alleviates Cerebral Ischemia\/Reperfusion Injury via Inhibiting Neural Ferroptosis Through Lipid Metabolic Reprogramming in\n                    <scp>MCAO<\/scp>\n                    Mice"],"prefix":"10.1002","volume":"32","author":[{"given":"Xinyun","family":"Li","sequence":"first","affiliation":[{"name":"School of Rehabilitation Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Children's Hospital, Zhejiang University School of Medicine National Clinical Research Center for Child Health  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangming","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou 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