Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a complex etiology and a protracted disease course. Active ingredients from traditional Chinese medicine (TCM), by leveraging the holistic regulatory advantages of anti-inflammatory activity, immune barrier preservation, and gut microbiota regulation, have shown unique therapeutic potential in the intervention of UC. Although bottlenecks such as unclear targets, fragmented mechanisms of action, and poor druggability constrain the clinical translation of TCM active ingredients, current research efforts are dedicated to overcoming these obstacles. This article reviews the latest research progress (2021–2026) on TCM active ingredients for UC treatment. It analyzes the anti-UC mechanisms from three core dimensions: chemical diversity and pharmacodynamic characteristics, validation of direct targets, and indirect regulation through the “gut microbiota–metabolite” axis. Moreover, it emphasizes recent breakthroughs in druggability optimization technologies, including carrier-based nano drug delivery systems (NDDS), carrier-free NDDS, co-delivery NDDS, and prodrug design strategy. Research demonstrates that TCM active ingredients achieve therapeutic effects by modulating inflammatory signaling networks, restoring intestinal immune homeostasis, repairing the mucosal barrier, and remodeling the gut microenvironment. Simultaneously, the application of novel delivery strategies effectively resolves issues such as poor solubility, low oral bioavailability, and insufficient colon targeting. Finally, this review suggests that future research on TCM active ingredients for UC therapy should concentrate on systematically clarifying multi-level mechanisms and designing clinically translatable smart drug delivery strategies, aiming to provide a theoretical basis and practical reference for promoting TCM modernization and innovative UC drug development.

Sojae Semen Praeparatum (SSP) is a traditional fermented soybean product with both dietary and medicinal uses in China. However, the dynamic metabolic changes and microbial community succession during SSP fermentation remain insufficiently characterized. In this study, untargeted metabolomics based on UHPLC-HRMS (Ultra-high-performance liquid chromatography-high-resolution mass spectrometry) was integrated with 16S rRNA gene and ITS amplicon sequencing to investigate metabolite remodeling, bacterial and fungal community succession, and their potential associations during SSP fermentation. Clear stage-dependent separation of metabolite profiles was observed, and 22,343 metabolic features were detected, of which 4281 were putatively annotated. Differential metabolites were mainly assigned to amino acids, dipeptides, lipids, carbohydrates, and isoflavones. Sucrose and other carbohydrates were progressively consumed during fermentation, while N-acetyl amino acids, short dipeptides, proline betaine and a range of lipid metabolites built up towards the later stages. The microbiota did not drift at random: amplicon sequencing resolved a clear successional sequence in both kingdoms. Bacteria converged on genera within the Enterobacteriaceae—mainly Enterobacter, Kosakonia and Citrobacter—whereas the fungi started out dominated by Rhizopus and ended in a co-dominant configuration of Aspergillus, Mucor and several minor taxa. When the two data sets were linked, the dominant taxa were associated with metabolites assigned to nitrogen, lipid and phenolic pathways. Procrustes analysis suggested a potential association between the fungal community and the metabolome, whereas the bacterial association was marginal; however, the difference in coupling strength between the two was not directly tested. These results provide preliminary evidence and a foundation for quality control and process optimization, but require validation across independent batches.