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.