In Vitro Glucuronidation and Sulfation of ?-Viniferin, a Resveratrol Dimer, in Humans and Rats.

ABSTRACT: ?-Viniferin is a resveratrol dimer that possesses antioxidant or anti-inflammatory activities. However little is known about the metabolism of this oligostilbene. This study was thus undertaken as a first approach to identify and characterize the metabolites of ?-viniferin and to describe the kinetic profile of their appearance in humans and rats. The glucuronides and sulfates of ?-viniferin were first obtained by chemical hemi-synthesis and were fully characterized by UPLC-MS and NMR spectroscopy. Then, ?-viniferin was incubated with human or rat S9 liver fractions that led to the formation of four glucuronoconjugates and four sulfoconjugates. In both species, ?-viniferin was subjected to an intense metabolism as 70 to 80% of the molecule was converted to glucuronides and sulfates. In humans, the hepatic clearance of ?-viniferin (V_max/K_m) for glucuronidation and sulfation were 4.98 and 6.35 µL/min/mg protein, respectively, whereas, in rats, the hepatic clearance for glucuronidation was 20.08 vs. 2.59 µL/min/mg protein for sulfation. In humans, three major metabolites were observed: two glucuronides and one sulfate. By contrast, only one major glucuronide was observed in rats. This strong hepatic clearance of ?-viniferin in human and rat could explain its poor bioavailability and could help to characterize its active metabolites.

SUBMITTER: Courtois A 

PROVIDER: S-EPMC6154661 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature