Conjugate Position of Glucuronide and Sulfate in Piceatannol\nDerivatives Affects the Stability and Hydrolytic Resistance of the\nConjugate in Biological Matrices

Piceatannol,\na stilbene compound, undergoes a comprehensive phase\nII metabolism mediated by UDP-glucuronosyltransferases (UGTs) and\nsulfotransferases (SULTs) in humans. Despite their well-documented\nbeneficial effects on health, their detailed pharmacokinetic fate,\nincluding the metabolite structure and properties, is poorly understood.\nThus, we determined the structure of seven glucuronides and six sulfates\ntransformed from piceatannol and its methylated derivatives in recombinant\nyeast cells expressing UGTs or SULTs. We evaluated their properties\nin human and rat plasma samples. The conjugate that was substituted\nat the 3′- or 4′-catecholic hydroxy moiety exhibited\nincreased stability. The sulfatase-mediated hydrolysis assay results\nin incomplete digestion or compound degradation of certain sulfates,\nsuggesting a potential risk of underestimation by using indirect quantification\nmethods. These findings emphasize the importance of an authentic standard\nfor accurate pharmacokinetic studies of phase II metabolites that\nwill be useful for understanding the mechanisms underlying the functional\ncontribution of piceatannol in the body.