{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T15:56:50Z","timestamp":1789833410720,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Tissue plasminogen activator (tPA)\u2013induced cerebral hemorrhagic transformation (HT) after ischemic stroke limits its clinical use widely. Pachymic acid, a main active component of\n                      <jats:italic>Poria cocos<\/jats:italic>\n                      , mitigates brain ischemia\/reperfusion injury, but its effect on tPA\u2010induced HT is unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A focal middle cerebral artery occlusion\/reperfusion model was established and administered with tPA and pachymic acid. Infarct volume and neurological function were assessed at 24\u2009h after reperfusion. Blood\u2013brain barrier (BBB) damage was evaluated using Evans blue leakage, immunofluorescence, and Western blot. Pachymic acid and PI3K protein interaction was identified using molecular docking, molecular dynamics (MD) simulation, and surface plasmon resonance (SPR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the tPA group, pachymic acid dose\u2010dependently improves neurological and motor functions, reduces infarct volume and hemorrhagic volume, and alleviates permeability and tight junction protein degradation of BBB after ischemic stroke, with the strongest effects observed at the highest dose. Molecular docking, MD simulation, and SPR results indicate that pachymic acid can directly bind to PI3K protein. Further experiments showed that the PI3K inhibitor LY294002 reversed pachymic acid's protective effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrated that pachymic acid protects the BBB by targeting PI3K to activate the PI3K\/Akt signaling pathway, thereby alleviating tPA\u2010induced HT after ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70782","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:51:10Z","timestamp":1771048270000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pachymic Acid Targets\n                    <scp>PI3K<\/scp>\n                    \/Akt Signaling Pathway to Attenuate\n                    <scp>tPA<\/scp>\n                    \u2010Induced Hemorrhagic Transformation After Ischemic Stroke"],"prefix":"10.1002","volume":"32","author":[{"given":"Yongshi","family":"Wu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8343-6787","authenticated-orcid":false,"given":"Ruoqi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yige","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Zhejiang Chinese Medical University  Hangzhou 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