Piceatannol exhibits potential food-drug interactions through the inhibition of human UDP-glucuronosyltransferase (UGT) in Vitro.

Abstract Piceatannol is a natural polyphenol compound found in passion fruit and blueberry with several biological activities. However, it is unclear whether piceatannol affects the activity of human UDP-glucuronosyltransferases (UGTs) enzymes. The present study aims to assess the potential inhibitory effect of piceatannol against UGTs enzymes, as well as to evaluate its potential food-drug interactions risk via UGTs inhibition. We systematically evaluated the inhibitory effects of piceatannol on UGTs using high-performance liquid chromatography by measuring the formation rates for 4-methylumbelliferoneglucuronide and imipramine N-glucuronide. The results indicated that piceatannol displayed broad-spectrum inhibition against human UGTs. Kinetic analysis showed that inhibition of piceatannol on UGT1A6 and UGT1A7 followed noncompetitive inhibition mechanism, while the inhibition on UGT1A8 and UGT1A9 obeyed competitive and mixed inhibition mechanism, respectively. The quantitative prediction of risks showed that the coadministration of piceatannol with drugs primarily cleared by UGT1A6, UGT1A7, UGT1A8, and UGT1A9 may result in potential food-drug interaction. In conclusion, additional caution should be taken when piceatannol and food containing piceatannol are co-administered with drugs metabolized by UGTs.