Integrated Network Pharmacology Analysis and Experimental Validation of Zadi-5 Against Coronary Heart Disease.

Abstract

This study aimed to investigate the potential molecular mechanisms underlying the therapeutic effects of the traditional Mongolian medicine Zadi-5 on coronary heart disease (CHD). The active compounds of Zadi-5 were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their corresponding targets were retrieved from HERB. The GSE42148 dataset was used to analyze differentially expressed genes (DEGs) associated with CHD. A compound-target network and a disease-gene-target network were constructed, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Molecular docking was performed to predict binding modes. Furthermore, we employed a CHD model with high-fat diet-fed ApoE^-/- mice to explore the protective effects of Zadi-5 in CHD. A total of 250 targets related to the active compounds in Zadi-5 were identified. Additionally, 480 DEGs were screened from the GSE42148 dataset, and seven key targets (MPO, IFNG, TOP2A, PTGS2, CYP2J2, F7, and PPARG) were identified. Molecular docking predicted strong binding affinities between PPARG and the main active components of Zadi-5. Furthermore, Zadi-5 markedly enhanced the heart performance and reduced fibrotic and inflammatory responses in vivo. Zadi-5 effectively suppressed the levels of HIF-1α and increased the PPARG levels in ApoE^-/- mice post-myocardial infarction. These findings suggest that the active components of Zadi-5 may exert therapeutic effects in CHD by targeting PPARG, as revealed by network pharmacology and molecular docking analyses.