Elucidating the Mechanism of Action of the Astragalus–Ginseng Herb Pair in Treating Coronary Heart Disease: A Network Pharmacology and Experimental Validation Approach

To elucidate the mechanism of action of the Astragalus membranaceus – Panax ginseng herb pair in treating coronary heart disease (CHD) through network pharmacology combined with molecular docking and experimental validation. Active ingredients and target proteins were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. CHD-related targets were obtained from GeneCards and DrugBank. Overlapping targets were identified with a Venn diagram, and a protein–protein interaction network was built in STRING. Core targets were screened via topological analysis in Cytoscape 3.9.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed in Metascape. AutoDock Vina was used for molecular docking. In vitro , tumor necrosis factor (TNF)-α levels in HL-1 cells subjected to oxygen-glucose deprivation (OGD) were measured by ELISA, and the effect of mangiferin pretreatment on cell viability was assessed with a CCK-8 assay. Forty-one active ingredients and 207 putative targets were identified for the herbal pair, and 1843 CHD-related targets were collected; 67 overlapping therapeutic targets were obtained. Topological analysis yielded 27 core targets. GO terms were enriched in responses to lipopolysaccharide, toxic substances, and organic cyclic compounds; molecular functions included cytokine-receptor binding and transcription-factor binding; and cellular components were mainly membrane rafts and extracellular matrix. KEGG analysis highlighted the TNF, fluid-shear-stress, and NF-κB signaling pathways. Docking showed strong binding between key components and targets. In vitro experiments demonstrated that formononetin pretreatment significantly reduced OGD-induced TNF-α levels and improved HL-1 cell viability. The A. membranaceus – P. ginseng combination herb pair exerts anti-CHD effects via multiple bioactive ingredients ( e.g., formononetin, quercetin, isorhamnetin, ginsenoside Rh2, kaempferol) by targeting TNF, AKT1, PTGS2, and JUN and modulating pathways including the TNF and NF-κB signaling pathways.