Mechanistic Basis and Translational Potential of Traditional Chinese Medicine in the Treatment of Cholestasis: A Narrative Review.

Background: Cholestasis results from impaired bile formation, secretion, or flow and contributes to heterogeneous hepatobiliary disorders, including primary biliary cholangitis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cholestatic drug-induced liver injury, and cholestasis-associated fibrosis. Persistent bile acid retention drives hepatocyte and cholangiocyte injury, immune activation, gut-liver axis disruption, and fibrogenesis. Traditional Chinese medicine (TCM) has been investigated as a multi-component therapeutic approach, but its evidence strength and translational readiness remain uncertain. Objective: To synthesize mechanistic, clinical, and translational evidence on TCM-based interventions for cholestasis and identify evidence gaps relevant to future development. Methods: PubMed, Web of Science Core Collection, CNKI, Wanfang, VIP, and SinoMed were searched for publications from 1 January 2016 to 25 January 2026, supplemented by backward citation chasing. A sensitivity search of CNKI, Wanfang, VIP, and SinoMed was performed to reduce language bias. Eligible studies were mapped by cholestatic condition or model, intervention type, study design, mechanistic domain, clinical relevance, and evidence strength. Results: Eighty studies were included in the core evidence set. The evidence base was dominated by preclinical animal, in vitro, omics, pharmacokinetic, quality-control, and toxicology studies, with limited mature clinical evidence. Recurrent mechanisms involved FXR-centered bile acid homeostasis, transporter regulation, inflammatory and immune pathways, oxidative stress and regulated cell death, fibrogenic signaling, and gut-liver axis modulation. Clinical evidence was most developed for intrahepatic cholestasis of pregnancy, where adjunctive TCM plus ursodeoxycholic acid was associated with improvements in bile acids and pruritus. However, heterogeneity in formula composition, trial quality, endpoint selection, and safety reporting limits inference, particularly for maternal-fetal outcomes. Evidence for other cholestatic indications remains limited or largely preclinical. Conclusion: TCM provides pathway-linked therapeutic hypotheses and candidate compounds for cholestasis, but high-confidence translation requires standardized products, exposure-response characterization, causal target validation, robust safety and herb-drug interaction assessment, and adequately powered disease-specific trials using clinically meaningful endpoints.