Protective effects of Polygonum cuspidatum bioactive constituents against cholestatic liver injury: A mechanistic review.

Polygonum cuspidatum Sieb. et Zucc. has long been prescribed in Traditional Chinese Medicine for jaundice, hepatitis, and cholestasis. Its major stilbenes (polydatin, resveratrol) and anthraquinones (emodin, quercetin) exhibit clinically relevant hepatoprotective effects. To systematically summarize mechanistic evidence for P. cuspidatum and its bioactive constituents in experimental models of cholestatic liver injury (CLI) and to evaluate their translational potential. Materials and methods: Literature was retrieved from PubMed, Web of Science, Scopus, and CNKI through June 2025. Data on pharmacodynamics, signaling pathways, and efficacy endpoints were extracted and synthesized. Polydatin, resveratrol, emodin, and quercetin alleviate CLI by regulating bile-acid synthesis and transport via the farnesoid X receptor (FXR), pregnane X receptor (PXR), and bile salt export pump (BSEP); activating Nrf2-dependent antioxidant defenses; suppressing NF-κB–mediated inflammation; and inhibiting TGF-β-driven fibrogenesis. Multi-target effects were confirmed in α-naphthylisothiocyanate(ANIT), bile-duct-ligation, and genetic cholestasis models with dose-dependent biochemical and histological improvements. P. cuspidatum offers a multi-pathway therapeutic strategy for CLI. Rigorous clinical trials are warranted to define optimal dosing, safety profile, and efficacy in patients. [Display omitted]