Stereoselective Conjugation, Transport and Bioactivity of S- and R-Hesperetin Enantiomers in Vitro
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- 作者：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.
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2010
- 出版时间：May 26, 2010
- 年：2010
- 卷：58
- 期：10
- 页码：6119-6125
- 全文大小：808K
- 年卷期：v.58,no.10(May 26, 2010)
- ISSN：1520-5118
文摘
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.