Bilirubin, as a major endogenous substance in the human body, plays anti-inflammatory, antioxidant, and cytoprotective roles within physiological ranges, serving a critical function in maintaining metabolic balance of endogenous substances. Bilirubin metabolism is a complex physiological process regulated by multiple factors, relying on UGT1A1 enzyme catalysis and transporter protein modulation to sustain substance homeostasis. Based on the theory of traditional Chinese medicine (TCM) channel tropism and the principle of visceral syndrome differentiation, liver-channel-tropic herbs can guide medications to specific viscera and meridians, exerting targeted therapeutic effects. These herbs regulate bilirubin metabolic disorders through multi-target mechanisms, including upregulating UGT1A1 enzyme activity to promote bilirubin conjugation, modulating MRP2/OATP expression to enhance bilirubin transport, attenuating oxidative stress to reduce hepatocyte damage, inhibiting inflammatory cytokines to restore metabolic enzyme activity, activating CAR signaling pathways to regulate bile acid homeostasis. This review summarizes the mechanisms by which TCM regulates bilirubin metabolism, focuses on the role of liver meridian-targeting TCM to provide a basis for its rational clinical use, and studies the effects of liver meridian-targeting TCM on bilirubin metabolism from its core mechanisms to guide its rational use and provide new ideas for the research and development of traditional Chinese medicine. This review summarizes the mechanisms by which TCM regulates bilirubin metabolism, focusing on the actions of herbs that enter the liver meridian. Starting from the core mechanisms, it explores how liver meridian-entering herbs significantly impact bilirubin metabolism. Some of these herbs demonstrate dual-directional regulatory effects on bilirubin metabolism. This understanding guides their rational clinical use, provides novel ideas for TCM research and development, and promotes the modernization of TCM studies.

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