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基于网络药理学的绝经后心肌梗死后更年安二仙合剂作用机制研究。

Mechanism of Action of NvZhen ErXian HeJi in Ovariectomized Rats with Myocardial Infarction based on Network Pharmacology.

机构信息

Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

Heart Center of Xinxiang Medical University, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

出版信息

Curr Pharm Des. 2024;30(39):3116-3130. doi: 10.2174/0113816128308824240719093114.

DOI:10.2174/0113816128308824240719093114
PMID:39161145
Abstract

OBJECTIVE

NvZhen ErXian HeJi (NZEXHJ) is used to treat perimenopausal syndrome (PS), but its effect on perimenopausal coronary heart disease is unclear. Furthermore, the aim of this research is to study the effect of NZEXHJ on perimenopausal coronary heart disease (PMCHD) in a rat model based on a network pharmacology approach.

MATERIALS AND METHODS

Based on network pharmacological analysis combined with molecular docking, we predicted the potential therapeutic target and pharmacological mechanism of NZEXHJ in the treatment of PMCHD. We used an ovariectomized rat (OVR) model to understand the effect of NZEXHJ on myocardial injury and further verified the target of NZEXHJ in the intervention of PMCHD.

RESULTS

We selected 52 active components of NZEXHJ against PMCHD and an intersection of their targets on network pharmacology, to which SCN5A, SER1, AR, and PGR were significantly correlated. The protein- protein interaction network revealed CASP3, CXCL8, IL6, MAPK1, TNF, TP53, and VEGFA in the treatment of PMCHD with NZEXHJ. Kaempferol, luteolin, and mistletoe presented good affinity towards the aforementioned targets by Molecular docking NZEXHJ exerted protecting cardiomyocytes for OVR. The mechanism was related to a reduction in the expression levels of the CXCL8, TNF, and regulating PI3K-Akt signaling pathways.

CONCLUSION

This study reveals the potential multi-component, multi-target, and multi-pathway pharmacological effects of NZEXHJ and predicts its protection against myocardial infarction in ovariectomized rats through the PI3K Akt pathway, providing a theoretical basis for the treatment of PMCHD.

摘要

目的

宁心安神合剂(NZEXHJ)用于治疗围绝经期综合征(PS),但其对围绝经期冠心病(PMCHD)的作用尚不清楚。此外,本研究旨在通过网络药理学方法研究 NZEXHJ 对大鼠围绝经期冠心病的影响。

材料和方法

基于网络药理学分析结合分子对接,预测 NZEXHJ 治疗 PMCHD 的潜在治疗靶点和药理机制。我们使用去卵巢大鼠(OVR)模型来了解 NZEXHJ 对心肌损伤的影响,并进一步验证 NZEXHJ 干预 PMCHD 的靶点。

结果

我们从 NZEXHJ 中选择了 52 种治疗 PMCHD 的活性成分及其网络药理学中的靶点交集,其中 SCN5A、SER1、AR 和 PGR 与 NZEXHJ 显著相关。蛋白质-蛋白质相互作用网络显示,在 NZEXHJ 治疗 PMCHD 中,CASP3、CXCL8、IL6、MAPK1、TNF、TP53 和 VEGFA 起重要作用。分子对接表明,NZEXHJ 对上述靶点具有良好的亲和力。NZEXHJ 对 OVR 具有保护心肌细胞的作用。其机制与降低 CXCL8、TNF 的表达水平以及调节 PI3K-Akt 信号通路有关。

结论

本研究揭示了 NZEXHJ 的潜在多成分、多靶点、多途径的药理作用,并通过 PI3K-Akt 通路预测其对去卵巢大鼠心肌梗死的保护作用,为治疗 PMCHD 提供了理论依据。

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Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?重新思考更年期激素治疗:针对谁、什么、何时以及多长时间?
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