Based on previous research conducted by our team on the components of Poria active ingredient (PAI),and utilizing the active ingredients identified from the TCMSP platform,network pharmacology was employed to predict the targets and signaling pathways of PAI in ulcerative colitis (UC) treatment.A protein-protein interaction network and an “PAI-target-disease-pathway” network were constructed,and molecular docking simulations using AutoDock were performed to verify the binding affinity between the key components of PAI and core targets.Subsequently,a mouse model of UC was induced using 3% dextran sulfate sodium for experimental validation.The network pharmacology results indicated that 52 active components,including Poria acid,were screened from PAI,which shared 256 common targets with UC,primarily involving cancer pathways,tumor necrosis factor (TNF) signaling,and mitogen-activated protein kinase (MAPK) signaling pathways.Animal experiments confirmed the successful establishment of a UC mouse model.Compared to the model group,PAI improved the weight loss and reduced colon length in UC mice,and significantly elevated the disease activity index (DAI) score.Hematoxylin and eosin staining showed that PAI effectively ameliorated colon tissue damage and restored intestinal barrier function.The treatment significantly reduced serum levels of lipopolysaccharide and D-lactate,improved intestinal permeability,and ameliorated intestinal mucosal injury.Real-time fluorescence quantitative PCR and Western blot analyses demonstrated that PAI significantly inhibited the gene expression of inflammatory cytokines such as interleukin-1β (IL-1β),interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α).Furthermore,they significantly upregulated the expression of tight junction proteins,including Occludin and Claudin-1,and downregulated the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylation of c-Jun N-terminal kinase (p-JNK) in the MAPK signaling pathway.In conclusion,PAI can improve ulcerative colitis by inhibiting the TNF/MAPK signaling pathway,suppressing the inflammatory response,and repairing intestinal barrier function.