Investigation of Anti‐Apoptotic Effects and Mechanisms of Astragaloside <scp>IV</scp> in a Rat Model of Cerebral Ischemia–Reperfusion Injury
Li Yu, Weifeng Jin, Defang Deng, Yiru Wang, Qianqian Chen, Yangyang Zhang, Haitong Wan, Yunxiang Chen, Ying Chen, Yu He, Lijiang Zhang
Abstract
BACKGROUND: Ischemic stroke is a prevalent and life-threatening cerebrovascular disease that is challenging to treat and associated with a poor prognosis. Astragaloside IV (AS-IV), a primary bioactive component of Astragali radix, has demonstrated neuroprotective benefits in previous studies. This study aimed to explore the mechanisms through which AS-IV may treat cerebral ischemia-reperfusion injury (CIRI). METHODS: Network pharmacology was employed to identify key targets and pathways of AS-IV in CIRI therapy, combined with molecular docking to predict binding affinity. Male Sprague-Dawley rats were randomly assigned to sham, MCAO/R, AS-IV, SP600125 (JNK inhibitor), AS-IV + SP600125, and 3-n-Butylphthalide (NBP) groups. Neurobehavioral deficits were assessed, and brain tissue damage was visualized through 2,3,5-triphenyltetrazolium chloride, H&E, and TUNEL staining. Immunohistochemistry was employed to detect CytC- and caspase-3-positive cells, while Western blotting, qPCR, and ELISAs were used to analyze apoptosis-related markers. RESULTS: . JNK inhibition reduced infarcted brain areas, improved neurological function, reduced pathological brain tissue damage, and inhibited apoptosis, with AS-IV achieving similar neuroprotective effects. Both AS-IV and SP600125 reduced p-JNK, Bid, CytC, Apaf-1, caspase-3, and cleaved caspase-3 levels in rats while decreasing CytC, caspase-3, and caspase-9 levels in serum. CONCLUSION: AS-IV may suppress apoptosis partly through the modulation of JNK/Bid signaling, exerting neuroprotective effects. These findings support the potential development of AS-IV-based therapies for stroke treatment.