Stereoselective conjugation, transport and bioactivity of S- and R-hesperetin enantiomers in vitro

Walter Brand, Jia Shao, Elisabeth F. Hoek-Van Den Hil, Kathelijn N. Van Elk, Bert Spenkelink, Laura H.J. De Haan, Maarit J. Rein, Fabiola Dionisi, Gary Williamson, Peter J. Van Bladeren, Ivonne M.C.M. Rietjens

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34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6119-6125
Number of pages7
JournalJournal of Agricultural and Food Chemistry
Volume58
Issue number10
DOIs
Publication statusPublished - 26 May 2010
Externally publishedYes

Keywords

  • Chirality
  • Conjugation
  • Flavonoid
  • HPLC
  • Stereoselectivity

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