Mechanisms and Research Advances of Traditional Chinese Medicine Intervention for Primary Sclerosing Cholangitis Based on the Gut-Liver Axis Theory

Abstract

Background & Objective: Primary sclerosing cholangitis (PSC) is a refractory chronic cholestatic liver disease with limited disease-modifying therapies. Gut-liver axis dysregulation, characterized by gut microbiota dysbiosis, intestinal barrier impairment and bile acid metabolism disorder, serves as the core pathological driver of PSC progression. This review aims to systematically elucidate the pharmacological mechanisms and clinical staged strategies of traditional Chinese medicine (TCM) for PSC targeting the gut-liver axis, and to provide theoretical references for integrative PSC management. Methods: Relevant domestic and international studies on TCM interventions for PSC and cholestatic liver diseases were retrieved and synthesized. The pathological mechanisms of the gut-liver axis in PSC were summarized, and the scientific consistency between the gut-liver axis network and TCM theory of concurrent liver and intestinal disorders was analyzed. The multi-target mechanisms and clinical application strategies of TCM formulas, active components and extracts were sorted out from three dimensions: microbiota regulation, barrier repair and anti-fibrosis. Results: TCM exerts holistic therapeutic effects via multi-target regulation: it remodels gut microbiota structure and modulates bile acid metabolism to activate FXR/TGR5 receptors; upregulates tight junction proteins (ZO-1, Occludin) to repair the intestinal mucosal barrier and block endotoxin translocation; and inhibits the TLR4/NF-κB and TGF-β1/Smad pathways to suppress intrahepatic inflammatory cascade and biliary fibrosis. Clinically, a three-stage integrative strategy can be established: intestine-clearing and choleretic therapy in the early stage, spleen-fortifying and intestine-securing therapy in the middle stage, and stasis-resolving and collateral-dredging therapy in the late stage. Conclusion: TCM intervention targeting the gut-liver axis exerts unique multi-component and multi-target advantages against PSC, which compensates for the limitations of Western medicine monotherapy. Future studies should adopt multi-omics technologies to clarify the causal relationship between TCM-modulated microbiota and host metabolism, and carry out high-quality clinical trials to support precision integrative therapy.