{"title":"黄芪甲苷对大鼠脑缺血再灌注损伤模型的抗凋亡作用及机制研究。","authors":"Li Yu, Weifeng Jin, Defang Deng, Yiru Wang, Qianqian Chen, Yangyang Zhang, Haitong Wan, Yunxiang Chen, Ying Chen, Yu He, Lijiang Zhang","doi":"10.1111/cns.70209","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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 <i>Astragali radix</i>, 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).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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<sup>−1</sup>. 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.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705586/pdf/","citationCount":"0","resultStr":"{\"title\":\"Investigation of Anti-Apoptotic Effects and Mechanisms of Astragaloside IV in a Rat Model of Cerebral Ischemia–Reperfusion Injury\",\"authors\":\"Li Yu, Weifeng Jin, Defang Deng, Yiru Wang, Qianqian Chen, Yangyang Zhang, Haitong Wan, Yunxiang Chen, Ying Chen, Yu He, Lijiang Zhang\",\"doi\":\"10.1111/cns.70209\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Ischemic stroke is a prevalent and life-threatening cerebrovascular disease that is challenging to treat and associated with a poor prognosis. 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引用次数: 0
摘要
背景：缺血性脑卒中是一种常见的危及生命的脑血管疾病，治疗具有挑战性，且预后较差。黄芪甲苷（Astragaloside IV, AS-IV）是黄芪的主要生物活性成分，在以往的研究中已证明具有神经保护作用。本研究旨在探讨AS-IV治疗脑缺血再灌注损伤（CIRI）的机制。方法：采用网络药理学方法鉴定AS-IV在CIRI治疗中的关键靶点和通路，结合分子对接预测结合亲和力。雄性Sprague-Dawley大鼠随机分为sham组、MCAO/R组、AS-IV组、SP600125 （JNK抑制剂）组、AS-IV + SP600125组和3-n-丁苯酞（NBP）组。评估神经行为缺陷，并通过2,3,5-三苯四氮氯化铵、H&E和TUNEL染色观察脑组织损伤。免疫组织化学检测CytC-和caspase-3阳性细胞，Western blotting、qPCR和elisa检测凋亡相关标志物。结果：共鉴定出48个AS-IV预测参与CIRI治疗的关键靶点，富集在136个通路中。AS-IV有效结合48个靶点中的前5个靶点，以及与c-Jun n -末端激酶(JNK)/Bid通路相关的靶点，结合能值低于-5.0 kJ·mol-1。JNK抑制可减少脑梗死面积，改善神经功能，减少病理性脑组织损伤，抑制细胞凋亡，AS-IV具有类似的神经保护作用。AS-IV和SP600125均能降低大鼠血清中p-JNK、Bid、CytC、Apaf-1、caspase-3和cleaved - caspase-3水平，同时降低血清中CytC、caspase-3和caspase-9水平。结论：AS-IV可能部分通过调控JNK/Bid信号通路抑制细胞凋亡，发挥神经保护作用。这些发现支持了基于as - iv的中风治疗的潜在发展。
Investigation of Anti-Apoptotic Effects and Mechanisms of Astragaloside IV in a Rat Model of Cerebral Ischemia–Reperfusion Injury
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.
期刊介绍：
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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