Article

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

Division of Toxicology, Wageningen University, Tuinlaan 5, PO Box 8000, 6703 HE Wageningen, The Netherlands.
Journal of Agricultural and Food Chemistry (Impact Factor: 3.11). 05/2010; 58(10):6119-25. DOI: 10.1021/jf1008617
Source: PubMed

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.

0 Bookmarks
 · 
143 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: doi: 10.1021/ie300211e
    Industrial & Engineering Chemistry Research 04/2012; 51(18):6586-6590. · 2.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Identification of metabolites is a major challenge in biological studies and relies in principle on mass spectrometry (MS) and nuclear magnetic resonance (NMR) methods. The increased sensitivity and stability of both NMR and MS systems have made dereplication of complex biological samples feasible. Metabolic databases can be of help in the identification process. Nonetheless, there is still a lack of adequate spectral databases that contain high quality spectra, but new developments in this area will assist in the (semi-)automated identification process in the near future. Here, we discuss new developments for the structural elucidation of low abundant metabolites present in complex sample matrices. We describe how a recently developed combination of high resolution MS multistage fragmentation (MS n) and high resolution one dimensional (1D)-proton (1 H)-NMR of liquid chromatography coupled to solid phase extraction (LC-SPE) purified metabolites can circumvent the need for isolating extensive amounts of the compounds of interest to elucidate their structures. The LC-MS-SPE-NMR hardware configuration in conjunction with high quality databases facilitates complete structural elucidation of metabolites even at sub-microgram levels of compound in crude extracts. However, progress is still required to optimally exploit the power of an integrated MS and NMR approach. Especially, there is a need to improve and expand both MS n and NMR spectral databases. Adequate and user-friendly software is required to assist in candidate selection based on the comparison of acquired MS and NMR spectral information with reference data. It is foreseen that these focal points will contribute to a better transfer and exploitation of structural information gained from diverse analytical platforms.
    Metabolomics 03/2013; · 4.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study is to investigate the in vitro metabolism of hesperetin, a bioflavonoid. Hesperetin was incubated with rat liver microsomes in the presence of NADPH and UDP-glucuronic acid for 30 min. The reaction mixture was analyzed by liquid chromatography-ion trap mass spectrometer and the chemical structures of hesperetin metabolites were characterzed based on their MS/MS spectra. As a result, a total of five metabolites were detected in rat liver microsomes. The metabolites were identified as a de-methylated metabolite (eriodictyol), two hesperetin glucuronides, and two eriodictyol glucuronides.
    Mass Spectrometry Letters. 01/2011; 2(1).

Full-text

Download
75 Downloads
Available from
Jun 3, 2014