{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:18:46Z","timestamp":1792185526829,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"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":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cerebral ischemic stroke (CIS) is a debilitating neurological condition lacking specific treatments. Cerebral ischemia\/reperfusion injury (CIRI) is a critical pathological process in CIS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to explore the protective effects of panaxadiol (PD) against oxidative stress\u2010induced neuronal apoptosis in CIS\/CIRI and its underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>An MCAO mouse model was established to investigate the therapeutic effects of PD in\u00a0vivo. Network pharmacology and molecular docking techniques were used to predict PD's anti\u2010CIS targets. The protective effects of PD were further validated in\u00a0vitro using oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R)\u2010treated HT22 cells. Finally, core targets were verified through combined in\u00a0vivo and in\u00a0vitro experiments to elucidate the mechanisms of PD in treating CIS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>PD exhibited significant neuroprotective activity, demonstrated by restoration of behavioral performance, reduced infarct volume, and decreased neuronal apoptosis in mice. Network pharmacology analysis identified 24 overlapping target genes between PD and CIS\u2010related targets. The hub genes, PTGS2, SERPINE1, ICAM\u20101, STAT3, MMP3, HMOX1, and NOS3, were associated with the HIF\u20101\u03b1 pathway, which may play a crucial role in PD's anti\u2010CIS effects. Molecular docking confirmed the stable binding of PD to these hub genes. Both in\u00a0vitro and in\u00a0vivo experiments further confirmed that PD significantly mitigates neuronal apoptosis and oxidative stress induced by CIS\/CIRI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PD significantly counteracts CIS\/CIRI by modulating the JAK3\/STAT3\/HIF\u20101\u03b1 signaling pathway, making it a promising therapeutic agent for treating CIS\/CIRI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70233","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T05:25:07Z","timestamp":1739769907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Panaxadiol Attenuates Neuronal Oxidative Stress and Apoptosis in Cerebral Ischemia\/Reperfusion Injury via Regulation of the\n                    <scp>JAK3<\/scp>\n                    \/\n                    <scp>STAT3<\/scp>\n                    \/\n                    <scp>HIF<\/scp>\n                    \u20101\u03b1 Signaling Pathway"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2262-866X","authenticated-orcid":false,"given":"Jiabin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei Province People's Republic of China"},{"name":"Wuhan University  Wuhan Hubei Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lei","sequence":"additional","affiliation":[{"name":"Wuhan University  Wuhan Hubei Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Naval Aviation University of Chinese People's Liberation Army  Yantai Shandong 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