From intestine to liver: A review of the pathological mechanisms of ulcerative colitis-induced secondary liver injury and targeted therapies with medicinal.

This review systematically integrates the multi-level pathological mechanisms of the gut-liver axis (GLA) in ulcerative colitis (UC)-secondary liver injury (SLI) and the multi-target intervention network of natural bioactive compounds, elucidating the synergistic therapeutic logic of "barrier repair - inflammation suppression - microbiota remodeling - signal regulation." To systematically review the pathological mechanisms underlying UC-induced SLI and explore the targeted therapeutic effects and molecular mechanisms of natural bioactive compounds intervening through the GLA, this study adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines. A systematic search and analysis of literature published between 2015 and 2025 in the PubMed and Web of Science databases was conducted, focusing on the pharmacological effects of natural active ingredients such as polysaccharides, polyphenols, terpenoids, alkaloids, peptides, microbial extracts, and probiotics. Research indicates that natural bioactive compounds ameliorate UC and SLI through multi-target mechanisms, with key pathways including: (1) upregulating tight junction protein expression to restore intestinal barrier integrity; (2) modulating intestinal microbiota homeostasis to promote the production of short-chain fatty acids and secondary bile acids; (3) inhibiting TLR4/NF-κB and NOD-like receptor protein 3 inflammasome signaling pathways; (4) regulating the bile acid-FXR-TGR5 signaling axis and the tryptophan/AhR pathway; (5) balancing immune homeostasis of Th17/Treg and macrophage polarization, thereby blocking the pathological cascade of ``intestinal barrier disruption - microbial translocation - hepatic inflammation.'' By virtue of their multi-dimensional regulation of the GLA, natural bioactive compounds offer a safe and multi-targeted therapeutic strategy for UC-related liver injury. However, translational bottlenecks remain, including low oral bioavailability and efficacy heterogeneity, due to individual differences in microbiota. This review provides a theoretical basis for their further development as pharmaceuticals or functional foods and emphasizes the need for high-quality randomized controlled trials to validate their clinical efficacy and safety.