Study on the Mechanism of Zhenwu Decoction in Treating Chronic Heart Failure Based on Network Pharmacology

OBJECTIVE To explore the mechanism of Zhenwu decoction in treating chronic heart failure(CHF) through network pharmacology. METHODS Candidate compounds in Zhenwu decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). SwissTargetPrediction platform was used to predict candidate targets, the targets of the corresponding compounds in TCMSP were supplemented. Uniprot database was used to convert target proteins into gene names. Genes related to CHF were obtained by CTD and TTD databases, taking the intersection of Zhenwu decoction target(gene) and CHF-related gene as the potential target of Zhenwu decoction in the treatment of CHF. The intersection gene was submitted to STRING11.0 online database for protein interchange analysis, the network diagram of protein interaction was drawn by using network visualization software Cytoscape 3.7.1. By using Excel, the network of Zhenwu decoction-potential compound-potential target was constructed, Cytoscape 3.7.1 was used for visualization. Path enrichment analysis was performed through RStudio's clusterProfiler package. Molecular docking techniques were used to validate the interactions between key targets and compounds. RESULTS There were 59 compounds of Zhenwu decoction which were screened by setting OB and DL values. After 36 intersection genes were obtained and chemical components without intersection genes (targets) were eliminated, 49 compounds were finally screened. A total of 36 articles were obtained by KEGG enrichment analysis, 13 of which were related to CHF. The results of molecular docking showed that the main active ingredients of Zhenwu decoction had a good combination with the key targets of heart failure. Deoxyaconitine, 3b-acetoxyatractylone, kaempferol, paeoniflorin, stigmasterol and b-sitosterol were the main active ingredients of Zhenwu decoction, interleukin 6, nitric oxide synthase 3, heme oxygenase 1, prostaglandin G/H synthase 2 and catalase were the main targets, main control cyclic guanylic acid-protein kinase G signaling pathway, renin secretion and calcium signaling pathway. CONCLUSION This study preliminarily clarified the mechanism of Zhenwu decoction in treating CHF through multi-component, multi-target and multi- pathway therapy, laying a foundation for further study on the pharmacodynamics basis and mechanism of Zhenwu decoction.