Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases

Chemico-biological Interactions
Xia LvLing Yang

Abstract

Amentoflavone (AMF), an abundant natural biflavonoid found in many medicinal plants, displays various beneficial effects including anti-inflammatory, anti-oxidative and anti-cancer. Despite the extensive studies on pharmacological activities, the toxicity or undesirable effects of AMF are rarely reported. In this study, the inhibitory effects of AMF on human UDP-glucuronosyltransferases (UGTs) were carefully investigated. AMF displayed strong inhibition towards most of human UGTs including UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4 and 2B17, with the IC50values ranging from 0.12 μM to 16.81 μM. Inhibition constants (Ki) of AMF against various human UGTs varied from 0.29 μM to 11.51 μM. Further investigation demonstrated that AMF was a noncompetitive inhibitor of UGT1A1 mediated NCHN-O-glucuronidation but functioned as a competitive inhibitor of UGT1A1 mediated 4-MU-O-glucuronidation. In addition, AMF was a competitive inhibitor of UGT1A4 mediated TFP-N-glucuronidation in both UGT1A4 and human liver microsomes, while functioned as a competitive inhibitor of UGT1A9 mediated propofol or 4-MU-O-glucuronidation. These findings demonstrated that AMF was a strong and broad-spectrum natural inhibitor of most human UGTs, which migh...Continue Reading

Citations

May 19, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yan Rong, Tony K L Kiang
Mar 6, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·José C J M D S Menezes, Marc F Diederich
Mar 9, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Yi KuangMin Ye
Mar 21, 2021·International Journal of Biological Macromolecules·Qi-Hang ZhouGuang-Bo Ge

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