675139-61-4Relevant articles and documents
Stereoselective conjugation, transport and bioactivity of S- and R-hesperetin enantiomers in vitro
Brand, Walter,Shao, Jia,Hoek-Van Den Hil, Elisabeth F.,Van Elk, Kathelijn N.,Spenkelink, Bert,De Haan, Laura H. J.,Rein, Maarit J.,Dionisi, Fabiola,Williamson, Gary,Van Bladeren, Peter J.,Rietjens, Ivonne M. C. M.
, p. 6119 - 6125 (2010)
The flavanone hesperetin ((±)-4′-methoxy-3′,5,7- trihydroxyflavanone) is the aglycone of hesperidin, which is the major flavonoid present in sweet oranges. Hesperetin contains a chiral C-atom and so can exist as an S- and R-enantiomer, however, in nature 2S-hesperidin and its S-hesperetin aglycone are predominant. The present study reports a chiral HPLC method to separate S- and R-hesperetin on an analytical and semipreparative scale. This allowed characterization of the stereoselective differences in metabolism and transport in the intestine and activity in a selected bioassay of the separated hesperetin enantiomers in in vitro model systems: (1) with human small intestinal fractions containing UDP-glucuronosyl transferases (UGTs) or sulfotransferases (SULTs); (2) with Caco-2 cell monolayers as a model for the intestinal transport barrier; (3) with mouse Hepa-1c1c7 cells transfected with human EpRE-controlled luciferase to test induction of EpRE-mediated gene expression. The results obtained indicate some significant differences in the metabolism and transport characteristics and bioactivity between S- and R-hesperetin, however, these differences are relatively small. This indicates that for these end points, including intestinal metabolism and transport and EpRE-mediated gene induction, experiments performed with racemic hesperetin may adequately reflect what can be expected for the naturally occurring S-enantiomer. This is an important finding since at present hesperetin is only commercially available as a racemic mixture, while it exists in nature mainly as an S-enantiomer.
