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Astragaloside IV (AS\u2010IV), a primary bioactive component of\n                      <jats:italic>Astragali radix<\/jats:italic>\n                      , has demonstrated neuroprotective benefits in previous studies. This study aimed to explore the mechanisms through which AS\u2010IV may treat cerebral ischemia\u2013reperfusion injury (CIRI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Network pharmacology was employed to identify key targets and pathways of AS\u2010IV in CIRI therapy, combined with molecular docking to predict binding affinity. Male Sprague\u2013Dawley rats were randomly assigned to sham, MCAO\/R, AS\u2010IV, SP600125 (JNK inhibitor), AS\u2010IV\u2009+\u2009SP600125, and 3\u2010n\u2010Butylphthalide (NBP) groups. Neurobehavioral deficits were assessed, and brain tissue damage was visualized through 2,3,5\u2010triphenyltetrazolium chloride, H&amp;E, and TUNEL staining. Immunohistochemistry was employed to detect CytC\u2010 and caspase\u20103\u2010positive cells, while Western blotting, qPCR, and ELISAs were used to analyze apoptosis\u2010related markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 48 key targets of AS\u2010IV predicted to be involved in the treatment of CIRI were identified, enriched in 136 pathways. AS\u2010IV was effectively bound to the top five targets from 48 targets, and those associated with the c\u2010Jun N\u2010terminal kinase (JNK)\/Bid pathway, with binding energy values below \u22125.0\u2009kJ\u00b7mol\n                      <jats:sup>\u22121<\/jats:sup>\n                      . JNK inhibition reduced infarcted brain areas, improved neurological function, reduced pathological brain tissue damage, and inhibited apoptosis, with AS\u2010IV achieving similar neuroprotective effects. Both AS\u2010IV and SP600125 reduced p\u2010JNK, Bid, CytC, Apaf\u20101, caspase\u20103, and cleaved caspase\u20103 levels in rats while decreasing CytC, caspase\u20103, and caspase\u20109 levels in serum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AS\u2010IV may suppress apoptosis partly through the modulation of JNK\/Bid signaling, exerting neuroprotective effects. These findings support the potential development of AS\u2010IV\u2010based therapies for stroke treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70209","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T04:40:43Z","timestamp":1736224843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Investigation of Anti\u2010Apoptotic Effects and Mechanisms of Astragaloside\n                    <scp>IV<\/scp>\n                    in a Rat Model of Cerebral Ischemia\u2013Reperfusion Injury"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4133-5483","authenticated-orcid":false,"given":"Li","family":"Yu","sequence":"first","affiliation":[{"name":"Qingshan Lake Science and Technology Innovation Center Hangzhou Medical College  Hangzhou China"},{"name":"School of Basic Medical Sciences Zhejiang Chinese Medical University  Hangzhou 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