Mechanism of action of NvZhen ErXian HeJi in ovariectomized rats with myocardial infarction based on network pharmacology

Abstract Purpose: NvZhen ErXian HeJi (NZEXHJ) is used to treat perimenopausal syndrome (PS), but its effect on perimenopausal coronary heart disease is unclear. To study the effect of NZEXHJ on perimenopausal coronary heart disease in a rat model based on a network pharmacology approach. Methods: Based on network pharmacological analysis combined with molecular docking, and that 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 verify 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, which SCN5A, SER1, AR, and PGR were significantly correlated. Protein-protein interaction network revealed CASP3, CXCL8, IL6, MAPK1, TNF, TP53, and VEGFA, in the treatment of PMCHD with NZEXHJ. The Kaempferol, luteolin, and mistletoe pre-sented 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 regulate PI3K-AKT signaling pathways. Conclusion: NZEXHJ may protect against myocardial injury after myocardial infarction in ovariectomized rats by regulating the PI3K-AKT signaling pathway through CXCL8, TNF, and other targets. Our study provides new ideas and targets for the treatment of perimenopausal coronary heart disease in the future.