Network pharmacology-based investigation of the mechanisms of Chrysanthemum indicum in treating insomnia

Objective: Using a network pharmacology approach, this study aimed to elucidate the molecular mechanisms of Chrysanthemum indicum (wild chrysanthemum flower) in alleviating insomnia. Methods: Insomnia-related targets were retrieved from GeneCards, the High-throughput Experiment- and Reference-guided database of Traditional Chinese Medicine (HERB), and the Encyclopedia of Traditional Chinese Medicine (ETCM). Overlapping targets between insomnia (6,181) and Chrysanthemum indicum (197) were identified. Protein–protein interaction (PPI) networks were constructed, and key genes were screened using CytoHubba, followed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Ultimately, a “disease–drug–key target–pathway” network was visualized, and literature review was conducted to confirm associations between candidate genes and insomnia. Results: 62 overlapping targets were identified, with ten hub genes highlighted: tumor protein p53 (TP53), tumor necrosis factor (TNF), Fos proto-oncogene (FOS), B-cell lymphoma 2 (BCL2), matrix metallopeptidase 9 (MMP9), transforming growth factor beta 1 (TGFB1), interleukin 6 (IL6), cyclin D1 (CCND1), caspase 3 (CASP3), and actin beta (ACTB). GO analysis indicated enrichment in γ-aminobutyric acid (GABA)-ergic (GABAergic) synaptic transmission and ion channel activity, while KEGG analysis revealed involvement in cancer-related, inflammatory, and metabolic pathways. Conclusions: Chrysanthemum indicum may improve sleep primarily by enhancing GABAergic signaling and attenuating neuroinflammation. These findings provide pharmacological evidence supporting its traditional use and potential development as a natural therapy for insomnia.