Research Progress on Bilirubin Metabolism based on FXR Agonist Regulation and the Treatment of Jaundice in Traditional Chinese Medicine

Abstract

Jaundice is a common clinical symptom caused by bilirubin metabolism disorders and is closely related to diseases of the liver, biliary tract and blood system. As a core nuclear receptor regulating bile acid metabolism, farnesol X receptor (FXR) maintains metabolic homeostasis by regulating bile acid synthesis (inhibiting CYP7A1), transport (promoting BSEP, MRP2), and enterohepatic circulation (inducing IBABP and FGF19). Traditional Chinese medicine takes ‘dissolving dampness and facilitating urination’ as the core treatment principle, showing multi-target advantages in the treatment of jaundice. Emodin and gardenoside and other active ingredients of traditional Chinese medicine can directly activate FXR, reduce bile acid synthesis through “downregulation of FXR→SHP→CYP7A1”, and promote bile acid and bound bilirubin excretion by upregulation of BSEP and MRP2; some traditional Chinese medicines can also enhance bilirubin-binding conversion by regulating UGT1A1 activity, or indirectly affect the FXR signalling pathway by remodeling the intestinal flora (e.g., inhibiting BSH activity and enriching beneficial bacteria) and regulating the microbiota-bile acid-FXR axis. Studies have shown that FXR agonists (such as obeticholic acid) and traditional Chinese medicine have a multi-dimensional intersection in regulating bilirubin metabolism, and the combination of the two forms an innovative strategy of “targeted intervention and systematic regulation”. In the future, it is necessary to deeply explore the structure-activity relationship and synergistic mechanism between traditional Chinese medicine ingredients and FXR, verify the efficacy through multi-centre trials, promote the development of new drugs and the advancement of precision diagnosis and treatment of integrated traditional Chinese and Western medicine, and provide a scientific basis for the treatment of jaundice and related hepatobiliary diseases.