Integrating network pharmacology and multidimensional bioinformatics: Mechanistic exploration of six food and medicine homology plants in coronary heart disease therapy.

Our study integrates network pharmacology with multiple bioinformatics approaches to systematically construct a framework for elucidating the therapeutic mechanisms of six food and medicine homology plants (FMHPs) in the treatment of coronary heart disease (CHD), with particular emphasis on their immunomodulatory potential and drug-like properties. Through network pharmacology, we identified 119 active ingredients and 951 associated targets by screening the TCMSP, SwissTargetPrediction, and Herb databases. Integrating differentially expressed genes (DEGs) from the GSE42148 dataset in the GEO database with weighted gene co-expression network analysis (WGCNA), 60 potential therapeutic targets were identified. Protein-protein interaction (PPI) network construction and functional enrichment analyses were then performed to characterize the interactions between FMHPs and CHD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed significant enrichment in pathways related to the lipopolysaccharide response and apoptotic signaling. Four hub genes were further identified using three independent machine learning algorithms. Mendelian randomization analysis validated their causal associations with CHD, while immune infiltration analysis suggested regulatory roles in activated the T cells CD4⁺ memory activated, naïve B cells, and other immune populations. Molecular docking confirmed favorable binding affinities between the core active ingredients and hub targets, and molecular dynamics simulations supported the stability of these complexes. Finally, ADMET predictions provided insights into the drug-likeness and pharmacological potential of these compounds. Collectively, this study provides novel insights into the multi-component and immunomodulatory mechanisms of FMHPs, potentially offering a theoretical foundation for their clinical application and future development as complementary therapeutic strategies for CHD.