Corylin induces UGT1A1 via PPARs/AhR and exerts hepatoprotection in mice

Uridine-5'-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) is a key enzyme in the regulation of bilirubin metabolism and detoxification of a variety of internal and external substances, and its insufficient function can lead to hyperbilirubinemia and affect the metabolic clearance of drugs, food additives, and environmental toxicants. However, there is a lack of safe and effective UGT1A1 inducers in the clinic. This study presents Corylin, an efficient UGT1A1 inducer identified from a series of natural flavonoids and isoflavonoids. Notably, Corylin demonstrated potent induction of intracellular UGT1A1. Furthermore, nuclear receptor reporter gene assays revealed that Corylin dose-dependently activated PPARs and AhR nuclear receptors, with the most robust activation observed in the PPARβ/δ subtype. Animal experiments indicated that Corylin exhibited favorable safety profiles and significant hepatoprotective effects in mice with APAP-induced liver injury, accompanied by marked UGT1A1 expression. Collectively, this study suggests that Corylin is a potential UGT1A1 inducer and a promising candidate for the intervention of liver-related disorders.