2. Academic Validation
  3. Investigation of Anti-Apoptotic Effects and Mechanisms of Astragaloside IV in a Rat Model of Cerebral Ischemia-Reperfusion Injury

Investigation of Anti-Apoptotic Effects and Mechanisms of Astragaloside IV in a Rat Model of Cerebral Ischemia-Reperfusion Injury

  • CNS Neurosci Ther. 2025 Jan;31(1):e70209. doi: 10.1111/cns.70209.
Li Yu 1 2 3,  Weifeng Jin 4,  Defang Deng 3,  Yiru Wang 3 5,  Qianqian Chen 2,  Yangyang Zhang 4,  Haitong Wan 2,  Yunxiang Chen 3,  Ying Chen 3,  Yu He 4,  Lijiang Zhang 1 3
Affiliations

Affiliations

  • 1 Qingshan Lake Science and Technology Innovation Center, Hangzhou Medical College, Hangzhou, China.
  • 2 School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
  • 3 Key Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, China.
  • 4 School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China.
  • 5 Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, China.
PMID: 39764606 DOI: 10.1111/cns.70209
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: A total of 48 key targets of AS-IV predicted to be involved in the treatment of CIRI were identified, enriched in 136 pathways. AS-IV was effectively bound to the top five targets from 48 targets, and those associated with the c-Jun N-terminal kinase (JNK)/Bid pathway, with binding energy values below -5.0 kJ·mol-1. 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.

Keywords

Apoptosis; Astragaloside IV; Cerebral ischemia–reperfusion injury; JNK/Bid; SP600125.

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