Target-centered network pharmacology and molecular docking reveal potential mechanisms and bioactive compounds of Zhigancao Decoction in insomnia–Arrhythmia comorbidity

This study aimed to investigate the potential mechanisms of Zhigancao Decoction (ZGCT) in insomnia–arrhythmia comorbidity using a target-centered network pharmacology and molecular docking approach. In addition, a refined candidate bioactive compound library was constructed. Active components of ZGCT were retrieved from TCMSP and HERB databases, and target prediction was performed using SwissTargetPrediction. Disease-related targets for insomnia and arrhythmia were obtained from GeneCards, followed by identification of intersection targets. A protein–protein interaction (PPI) network was constructed using STRING, and hub genes were identified via topological analysis and Maximal Clique Centrality (MCC) in Cytoscape. Functional enrichment analysis was performed using Metascape, and molecular docking was used to evaluate ligand–target interactions. A total of 84 active compounds and 193 associated targets were identified for ZGCT. Intersection analysis yielded 41 common targets. PPI network analysis identified 10 hub targets, including AKT1, PPARG, and MMP9. Based on a target-centered reverse screening strategy, 22 candidate bioactive compounds were identified, and molecular docking showed computationally favorable binding energies between key compounds and core targets. These compounds are associated with neuroendocrine, inflammatory, and cardiovascular signaling pathways. ZGCT is predicted to exert therapeutic effects on insomnia–arrhythmia comorbidity through a systems-level multi-target regulatory network involving neuroendocrine modulation, renin–angiotensin system-related pathways, and cardiovascular remodeling. The proposed target-centered reverse screening strategy provides a refined and interpretable framework for constructing a disease-specific bioactive compound library, offering potential directions for further experimental validation and drug development.