Exploration of the Mechanism of Warming Yang,Benefiting Heart,and Regulating Shen Therapy in the Treatment of Coronary Heart Disease and Depression Based on Oxidative Stress and Bioinformatics

HAN Huiying; LIU Zhaihua; CAO Hongxin

Abstract：Objective To study the molecular mechanism of warming heart prescription in the treatment of coronary heart disease with depression,and explore the action mechanism of warming Yang,benefiting heart,and regulating Shen therapy.Methods The active components of TCM were retrieved and screened through TCMSP,ETCM,Chemsrc,PubChem and SwissTarget Prediction databases to obtain drug targets.Gene Cards,DrugBank and TTD databases were used to obtain comorbidity targets.The construction of PPI network and obtaining core targets were carried out by STRING11.5.Cytoscape3.9.1 was used to establish the"drug-active ingredients-core targets"network to obtain the core components.Through Metascape,GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out,and visual charts were made by using microbioinformatics and synthetic analyzing important enrichment pathways.Cytoscape3.9.1 was used to analyze targets recruited to important pathways,obtain key genes,and correlated compounds.The molecular structures of protein receptors(key genes)and molecule ligands(correlated compounds)were obtained by RCSB PDB,TCMSP and PubChem databases.AutoDockTools1.5.6 and pymol,were used for molecular docking and visual presentation.Results There were 103 active components of Wenxin prescription and 5 core components,which were gomisin B,baicalein,naringenin,vitamin E and prostaglandin B1.There were 608 targets and 138 core targets,which were mainly recruited in AGE-RAGE pathway,JAK-STAT pathway,PI3K-AKT pathway and FOXO pathway.It may be involved in cell proliferation and apoptosis,cell morphology regulation and skeletal remodeling,cell cycle regulation,axonal transport,vascular endothelial growth,vascular tension and other cellular functions and biological processes.Between core gene and correlated compounds have reasonable docking conformation and feasible results.Conclusion Baicalein,naringenin and vitamin-E may be important components of Wenxin prescription in the treatment of coronary heart disease with depression.These compounds exert pharmacological effects by regulating AGE-RAGE pathway,JAK-STAT pathway,PI3K-AKT pathway and FOXO pathway through VEGFA,NFKB1,MAPK1 and other gene targets.In conclusion,warming Yang,benefiting heart,and regulating Shen therapy achieves the purpose of treating coronary heart disease with depression by reducing the oxidative stress reaction of myocardial cells and neurons to protect vascular endothelial growth and improve nerve function.It can promote anti-oxidation mechanism and scavenge oxidative stress as well as reduce the production of proinflammatory medium and inhibit inflammatory process by stabling redox reaction processes,thus adjusting the dynamic balance between cell proliferation and apoptosis to maintain homeostasis.At the same time,this study also indirectly indicated that the comorbidity mechanism of coronary heart disease and depression was related to oxidative stress.