To explore the mechanism of Zhigancao Decoction in treating arrhythmia based on network pharmacology.Methods:The active ingredients and targets of Zhigancao Decoction were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and BATMAN-TCM,and the disease targets of arrhythmia were screened out through GeneCards and OMIM.The common targets of the drug and the disease were obtained.String was used to construct a protein-protein interaction(PPI) network of targets,and Cytoscape 3.7.2 was used to screen key genes,which underwent topological data analysis by CytoNCA plug-in.Bioconductor and RX64 4.0.0 were adopted for GO enrichment and KEGG pathway enrichment analyses of common genes.The core proteins were subjected to molecular docking with core compound molecules in the PPI network using SwissDock.Results:A total of 171 compounds and 4 090 targets were screened out,and 435 targets related to arrhythmia were obtained.PPI results showed that in terms of degree,the top 6 genes were INS,KCNH2,SCN5A,CAV3,GJA1,and TNNI3.Topological data analysis revealed that in terms of degree,the top 5 genes were EGFR,HSPA8,NTRK1,ESR1,and HSP90AA1.Molecular docking results showed that most of the active ingredients and key targets of Zhigancao Decoction had high binding rates,with the lowest binding energy of SCN5A to lysine and KCNH2 to γ-aminobutyric acid.GO enrichment analysis showed that the therapeutic effect of Zhigancao Decoction was related to heart contraction,heart muscle contraction,heart process,striated muscle contraction,and heart contraction regulation.KEGG enrichment analysis showed that the therapeutic effect of Zhigancao Decoction was associated with adrenergic signal in cardiomyocytes,hypertrophic cardiomyopathy,cGMP-PKG signaling pathway,and dilated cardiomyopathy.Conclusion:Zhigancao Decoction is characterized by multi-component,multi-target,and multi-pathway in the treatment of arrhythmia.