A preclinical investigation into the potential associations of geraniin with ulcerative colitis alleviation through integrated multi-omics and in vivo analysis

Objective This study aims to investigate the potential molecular mechanisms and alleviating effects of geraniin, a natural polyphenol compound, within a murine model of ulcerative colitis (UC), thereby providing preclinical insights that may inform future translational strategies. Methods Potential targets of geraniin for UC were identified by screening databases such as the Comparative Toxicogenomics Database and SwissTargetPrediction. UC transcriptomic and single-cell data were sourced from GEO (GSE47908, GSE214695). Differential gene analysis used limma, co-expression modules via WGCNA, enrichment with ClusterProfiler for GO/KEGG, and immune cells via CIBERSORT. Single-cell analysis employed Seurat and AUCell to identify targeted subpopulations. In vivo , DSS-induced UC mice were grouped as control, model, and model + geraniin (30, 60 mg/kg). Effects were assessed by DAI, histopathology, Western blot, and immunofluorescence. Results Geraniin targeted 27 genes, which were integrated with 337 UC-related genes to construct a protein–protein interaction network. MCODE analysis identified a key subnetwork comprising 42 genes. GO and KEGG analyses suggested that the potential effects of geraniin may be linked to inflammatory pathways such as IL-17, TNF, and CXCR chemokine signaling. In the single-cell dataset GSE214695, AUCell scores indicated an enrichment of drug targets in macrophage and neutrophil clusters. In this murine model, in vivo experiments indicated that geraniin administration was associated with reduced DAI scores, improved colon length, and the alleviation of mucosal damage and inflammatory cell infiltration. Immunofluorescence analysis revealed that geraniin treatment was associated with a reduced presence of markers for M1 macrophages (F4/80+/CD86+), neutrophils, and NET formation (CitH3+/MPO+), while correlating with an increase in M2 macrophages markers (F4/80+/CD206+). Western blot analysis showed that geraniin treatment correlated with the downregulation of NOS2 and upregulation of PPARG expression, which may contribute to mitigating the inflammatory response observed in this model. Conclusion These findings suggest that geraniin is associated with the alleviation of DSS-induced UC in mice, potentially through the modulation of phenotypic markers related to macrophages and neutrophils.