Role of chaihu yujin decoction in cholecystitis: a systematic investigation integrating multi-omics and experimental...

To investigate the mechanism and effects of Chaihu Yujin Decoction (CYD) in the treatment of cholecystitis. This study employed an integrated network pharmacology and experimental approach to investigate CYD's mechanism against cholecystitis. Active components and targets of CYD were identified from TCMSP, ETCM, and BATMAN-TCM databases, while disease targets were obtained from GeneCards, PharmMapper, OMIM, and TTD. These shared targets were used to construct a PPI network via STRING and a herb-component-target network via Cytoscape. GO and KEGG enrichment analyses were performed using DAVID. Key components and targets were selected for molecular docking, with interaction stability further assessed by molecular dynamics simulations and validated in animal experiments. This study identified 208 potential active components from CYD and 122 shared targets between CYD and cholecystitis (i.e., the intersection of CYD-predicted targets and cholecystitis-associated targets). Enrichment analysis suggested potential therapeutic mechanisms involving apoptosis regulation, gene expression, and the HIF-1/PI3K-Akt pathways, although these predictions await direct experimental confirmation at the protein level. Molecular docking demonstrated strong binding affinity of CYD components to these targets, and molecular dynamics simulations confirmed stable ligand-protein interactions. In guinea pig models, CYD significantly mitigated cholecystitis. It markedly reduced levels of inflammatory mediators (COX-2, TNF-α, IL-6, IL-1β; P < 0.0001) and decreased gallbladder enlargement (high-dose, P = 0.0025) compared to the model group. Histopathological examination revealed that high-dose CYD most effectively alleviated mucosal atrophy and inflammatory cell infiltration, with only slight lymphocyte infiltration remaining. This study demonstrates that CYD alleviated cholecystitis by reducing inflammatory mediators and improving gallbladder mucosal integrity, providing a mechanistic rationale supported by in vivo efficacy data and computational target predictions for further preclinical and clinical investigation.