Study On The Potential Mechanism Of Xinkang Granule In The Treatment Of Dilated Cardiomyopathy (DCM) Based On Network Pharmacology

Objective: Dilated cardiomyopathy(DCM)is a common form of cardiomyopathy characterized by ventricular dilation and systolic dysfunction,and is the most common cause of heart failure(HF).Patients with DCM typically present with systolic heart failure on early,but diastolic dysfunction may develop as the disease progresses.Currently,despite the treatment’s success,some patients are still prone to refractory heart failure(HF)and sudden cardiac death(SCD),requiring costly heart transplants or mechanical support.This study explored the potential mechanism of Xinkang Granule in the treatment of DCM based on network pharmacology,and provided theoretical basis for subsequent studies.Methods: The main active ingredients and their action targets of Xinkang Granule were searched through TCMSP database and related literature.The active ingredients of the target could not be predicted in TCMSP database.After screening by Swissadme platform,the target prediction and supplement were made by Swinstargtprediction platform to construct the drug target database.DCM related targets were obtained through Gene Cards and OMIM databases,and a disease target library was established.The intersection of drug target library and disease target library was constructed by R language,and the Venn diagram was constructed.Compound-target network,PPI core network and pathway-gene network were constructed by String database,Cytoscape3.7.1 software and its internal plug-ins.Finally,GO enrichment and KEGG pathway annotation analysis were performed on the core network targets using David database.Results: 102 active components and 472 target genes of Xinkang Granule were screened out.2035 target genes of DCM were screened,160 key targets of Venn map of drugs and diseases were screened,and 12 genes in key position were screened by the construction of PPI core network.GO analysis(P <0.05 and target gene enrichment >10%)revealed 19 biological processes,19 cellular component expression processes,and 9 molecular function-related processes.KEGG analysis(P<0.05)showed 118 signaling pathways involved in oxidative stress,inflammatory response,immune response,glucose and lipid metabolism,regulation of cytoskeleton and other aspects.These include NF-κB signaling pathway,HIF-1 signaling pathway,PI3K-Akt signaling pathway,RAP1 signaling pathway,JAK-STAT signaling pathway,regulation of actin cytoskeleton,T cell receptor signaling pathway,starch and sucrose metabolism,inflammatory bowel disease(IBD),etc.Conclusion: Xinkang Granule plays a role in the treatment of DCM through multi-components,multi-targets and multi-channels,which will provide a reference for the mechanism of action,experimental research and new drug development of Xinkang Granule in the treatment of DCM.