Study On The Mechanism Of Yangxin Tongmai Decotion In The Treatment Of Coronary Heart Disease Based On Bioinformatics

Objective: The study aimed to screen the active compounds and targets of Yangxin Tongmai Decoction using bioinformatics research methods,and to investigate the mechanisms of Yangxin Tongmai Decoction in the treatment of coronary heart disease(CHD).Methods: The active compounds and targets of Yangxin Tongmai Decoction,including twelve Chinese herbal medicines,were searched from the TCMSP and BATMAN-TCM databases,and the target genes were identified in the Uniprot database.Cytoscape was used to construct the Chinese herbal medicine-active compound-gene network,and the network topology analysis was used to screen the core active compounds.The CHD chip data set GSE66360 was obtained from GEO database,and the differentially expressed genes were screened and intersected with the target genes of the effective compounds of Yangxin Tongmai Decoction to obtain the target genes.A PPI network of intersecting targets was constructed in Cytoscape and then the core genes and key active compounds were screened.The target genes were analyzed by GO and KEGG enrichment and visualized using the Bioconductor database.Key active compounds were obtained from Pub Chem database,target protein structures were obtained from PDB database,molecular docking was performed by Vina software,binding free energy was calculated and finally the results were visualized by Py MOL software.Results: The 251 active compounds of Yangxin Tongmai Decoction act on493 target genes.414 differentially expressed genes associated with CHD were obtained in the GEO microarray dataset,and 36 target genes were available from the intersection.Quercetin,lignan,kaempferol,baicalin,nobiletin and naringenin were the key active compounds.IL1 B,MMP9,CXCL8,PTGS2,VEGFA and JUN were the key genes.The response to lipopolysaccharide,cellular response to external stimuli and leukocyte migration are the main biological processes of the target genes.NF-κB signaling pathway,TNF signaling pathway,Toll-like receptor signaling pathway and IL-17 signaling pathway are the KEGG signaling pathways associated with CHD.Molecular docking showed that quercetin-JUN,Tanshinone IIA-JUN,naringenin-MAPK3 and lignan-NFKBIA binding activities were more significant.Conclusions:(1)Preliminarily,the study explore the mechanism of Yangxin Tongmai Decoction on treating CHD through multi-component,multi-target and multi-pathway.(2)The effects of Yangxin Tongmai Decoction on treatment of CHD are the actions of multiple active compounds,among which quercetin,lignan,kaempferol,baicalin,Nobiletin and naringenin are the core active compounds.(3)Yangxin Tongmai Decoction treats CHD mainly through core target genes such as IL1 B,MMP9,CXCL8,PTGS2,VEGFA and JUN.(4)Yangxin Tongmai Decoction prevents and treats CHD mainly through interacting biological processes such as response to lipopolysaccharide,cellular response to external stimuli and leukocyte migration.Yangxin Tongmai Decoction affects the development of CHD mainly through NF-κB signaling pathway,TNF signaling pathway,Toll-like receptor signaling pathway and IL-17 signaling pathway.(5)Molecular docking proves the binding activity of core compounds to core genes has good activities and the docking complexes are more stable.