Background: Ulcerative colitis (UC) is a diffuse nonspecific intestinal inflammation. Spleen-kidney Yang deficiency combined with liver stagnation is the most common symptom. Sishen Pills-Tongxie Yaofang (SSP-TXYF) is a traditional Chinese medicine (TCM) that is widely used in the treatment of this symptom. However, its pharmacological mechanism and active components remain unclear. Objective: This study elucidated the potential mechanism and active components of SSP-TXYF in the treatment of UC from the perspective of TCM syndrome. Methods: Metascape, STRING, and Cytoscape were used to explore the SSP-TXYF-compound-target-UC network and biological enrichment pathways, so as to screen the active compounds, key targets, and pathways of SSP-TXYF. Through the construction of a rat model with UC, the key targets and active components were verified after SSP-TXYF administration. Results: A total of 77 effective active chemical components, 208 potential targets, and 5 core target genes were screened out. Gene Ontology biological process items and Kyoto Encyclopedia of Genes and Genomes signaling pathways showed that SSP-TXYF played a role in regulating nerve-endocrine, cell proliferation and apoptosis, and immune-related pathways. The main compounds and the target protein exhibited a good binding ability in molecular docking. The results of animal experiments showed that SSP-TXYF could improve UC through IL-6, AKT1, PTGS2, CASP3, and JUN, and nobiletin and wogonin were identified as the main active components. Conclusions: This study suggests that nobiletin and wogonin are the main components of SSP -TXYF in the treatment of UC, which provides effective therapeutic targets and drugs for future clinical treatment of UC.

Influenza A virus (IAV) infection triggers excessive activation of PANoptosis—a coordinated form of programmed cell death integrating pyroptosis, apoptosis, and necroptosis—which contributes to severe immunopathology and acute lung injury. However, the molecular regulators that drive PANoptosis during IAV infection remain poorly understood. In this study, we integrated bulk and single-cell RNA sequencing (scRNA-seq) datasets to dissect the cellular heterogeneity and transcriptional dynamics of PANoptosis in the influenza-infected lung. PANoptosis-related gene activity was quantified using the AUCell, ssGSEA, and AddModuleScore algorithms. Machine learning approaches, including Support Vector Machine (SVM), Random Forest (RF), and Least Absolute Shrinkage and Selection Operator (LASSO) regression, were employed to identify key regulatory genes. scRNA-seq analysis revealed that PANoptosis activity was primarily enriched in macrophages and neutrophils. Integration of transcriptomic and computational data identified cathepsin B (CTSB) as a central regulator of PANoptosis. In vivo validation in an IAV-infected mouse model confirmed elevated expression of PANoptosis markers and upregulation of CTSB. Mechanistically, CTSB may facilitate NLRP3 inflammasome activation and promote lysosomal dysfunction-associated inflammatory cell death. These findings identify CTSB as a critical mediatoCTSBr linking lysosomal integrity to innate immune-driven lung injury and suggest that targeting CTSB could represent a promising therapeutic strategy to alleviate influenza-associated immunopathology.