Multi-Dimensional Mechanisms and Druggability Optimization Strategies of Active Ingredients from Traditional Chinese Medicine in the Treatment of Ulcerative Colitis

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.