Zhang Shiyu, Li Shijie, Li Xue, Wan Chen, Cui Lin, Wang Youping
Division of Cardiology and Central Laboratory, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Pharm Biol. 2025 Dec;63(1):250-263. doi: 10.1080/13880209.2025.2488994. Epub 2025 Apr 22.
Myocardial fibrosis is a common manifestation of end-stage cardiovascular disease, but there is a lack of means to reverse fibrosis. Astragaloside IV (AS-IV), the major active component of Fisch. ex Bunge Fabaceae, possesses diverse biological activities that have beneficial effects against cardiovascular disease.
This systematic review aims to summarize the anti-fibrosis effect of AS-IV in animal models (rats or mice only) and its underlying mechanisms, and provide potential directions for the clinical use of AS-IV.
PubMed, EMBASE, Web of Science, CNKI, Wanfang database, and SinoMed were searched from inception to 31 December 2024. The following characteristics of the included studies were extracted and summarized: animal model, route of administration, dose/concentration, measurement indicators, and potential mechanisms. The quality of the included studies was assessed used a 10-item scale from SYRCLE.
AS-IV represents a promising multi-target candidate for myocardial fibrosis treatment in the 24 eligible studies included in the analysis. This systematic review is the first to comprehensively evaluate the anti-fibrosis mechanisms of AS-IV across heterogeneous cardiovascular disease animal models, including myocardial infarction, hypertension, ischemia-reperfusion injury, and myocarditis. The underlying mechanisms of the anti-fibrosis effects of AS-IV may include collagen metabolism, anti-apoptosis, anti-inflammation and, pyroptosis, antioxidants, improving mitochondrial function, regulating senescence, etc. Current evidence remains preclinical, with critical gaps in toxicological profiles, human safety thresholds, and clinical adverse reaction data. Future research must integrate robust toxicological evaluations, optimized combination therapies, and adaptive clinical trials to validate translational potential.
心肌纤维化是终末期心血管疾病的常见表现，但缺乏逆转纤维化的方法。黄芪甲苷（AS-IV）是豆科植物膜荚黄芪的主要活性成分，具有多种生物学活性，对心血管疾病有益。
本系统评价旨在总结AS-IV在动物模型（仅大鼠或小鼠）中的抗纤维化作用及其潜在机制，并为AS-IV的临床应用提供潜在方向。
检索了从创刊至2024年12月31日的PubMed、EMBASE、Web of Science、中国知网、万方数据库和中国生物医学文献数据库。提取并总结纳入研究的以下特征：动物模型、给药途径、剂量/浓度、测量指标和潜在机制。使用SYRCLE的10项量表评估纳入研究的质量。
在分析纳入的24项合格研究中，AS-IV是治疗心肌纤维化的一个有前景的多靶点候选药物。本系统评价首次全面评估了AS-IV在包括心肌梗死、高血压、缺血再灌注损伤和心肌炎在内的异质性心血管疾病动物模型中的抗纤维化机制。AS-IV抗纤维化作用的潜在机制可能包括胶原代谢、抗凋亡、抗炎、焦亡、抗氧化、改善线粒体功能、调节衰老等。目前的证据仍处于临床前阶段，在毒理学特征、人体安全阈值和临床不良反应数据方面存在关键差距。未来的研究必须整合强有力的毒理学评估、优化的联合治疗和适应性临床试验，以验证其转化潜力。
