Insight of action mechanism of Astragaloside IV for relieving of cerebral ischemic injury in a rat model of middle cerebral artery occlusion reperfusion via proteomics and network pharmacology

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines Pub Date : 2025-04-10 DOI:10.1007/s11418-025-01892-9

Xin-Hua Zhu, Xin Yu, Xiang-Wen Kong, Yi Zhang, Si-Liang Jiang, Jun-Hong Chai, Jun Liang, Hai-Xue Kuang, Yong-Gang Xia

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引用次数: 0

Abstract

Astragaloside IV (AS-IV) is the principal active component of Astragalus membranaceus (fisch.) Bge. var. mongholicus (Bge.) Hsiao. This study aims to explore action mechanism of AS-IV for relieving of cerebral ischemic injury in a rat model of middle cerebral artery occlusion reperfusion (MCAO) via proteomics and network pharmacology. Pharmacodynamics experiments showed that AS-IV could effectively alleviate MACO-induced cerebral infarction, preserve the structural integrity of neurons, and promote the formation of Sol bodies. In addition, TMT quantitative proteomics revealed differential proteins (DEPs), e.g., DGKQ, PPT1, Gnai3, Gnal, PLA2G4A, and Ppp2ca. These DEPs might be closely related to AS-IV for the therapeutic effects on ischemic stroke. In combination with network pharmacology, the PLA2G4A was further identified as key target protein of AS-IV ascribed to its involvement in the regulation of inflammatory mediators in the TRP pathway. Ultimately, in vitro validation demonstrated that AS-IV offers neuroprotective effects by targeting the PLA2G4A, reducing the release of arachidonic acid (AA) and COX-2, and facilitating Ca²⁺ inflow into cells. This study provided a scientific basis on development and application of AS-IV for treating ischemic stroke.

Graphical abstract

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通过蛋白质组学和网络药理学研究黄芪甲苷缓解大鼠大脑中动脉闭塞再灌注模型脑缺血损伤的作用机制

黄芪甲苷（Astragaloside IV, AS-IV）是黄芪的主要活性成分。知母。蒙古变种（大）萧。本研究旨在通过蛋白质组学和网络药理学方法探讨AS-IV对大鼠大脑中动脉闭塞再灌注（MCAO）模型脑缺血损伤的缓解作用机制。药效学实验表明，AS-IV能有效缓解maco诱导的脑梗死，保持神经元结构完整性，促进Sol小体的形成。此外，TMT定量蛋白质组学发现了差异蛋白（DEPs），如DGKQ、PPT1、Gnai3、Gnal、PLA2G4A和Ppp2ca。这些DEPs可能与AS-IV对缺血性脑卒中的治疗作用密切相关。结合网络药理学，进一步确定PLA2G4A参与TRP通路中炎症介质的调控，是as - iv的关键靶蛋白。最终，体外验证表明，AS-IV通过靶向PLA2G4A，减少花生四烯酸（AA）和COX-2的释放，促进Ca2+流入细胞，具有神经保护作用。本研究为AS-IV治疗缺血性脑卒中的开发和应用提供了科学依据。图形抽象

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.