Stereoselective conjugation, transport and bioactivity of s- and R-hesperetin enantiomers in vitro.
Identifieur interne : 001996 ( Main/Exploration ); précédent : 001995; suivant : 001997Stereoselective conjugation, transport and bioactivity of s- and R-hesperetin enantiomers in vitro.
Auteurs : Walter Brand [Pays-Bas] ; 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. RietjensSource :
- Journal of agricultural and food chemistry [ 1520-5118 ] ; 2010.
English descriptors
- KwdEn :
- Animals, Biological Transport, Caco-2 Cells, Cell Line, Tumor, Citrus sinensis (chemistry), Cytosol (metabolism), Fruit (chemistry), Gene Expression (drug effects), Glucuronides (metabolism), Hesperidin (chemistry), Hesperidin (metabolism), Hesperidin (pharmacology), Humans, Intestine, Small (metabolism), Intestine, Small (ultrastructure), Liver Neoplasms, Experimental, Mice, Microsomes, Liver (metabolism), Response Elements (genetics), Stereoisomerism, Structure-Activity Relationship, Sulfonic Acids (metabolism), Transfection.
- MESH :
- chemical , chemistry : Hesperidin.
- chemical , metabolism : Glucuronides, Hesperidin, Sulfonic Acids.
- chemistry : Citrus sinensis, Fruit.
- drug effects : Gene Expression.
- genetics : Response Elements.
- metabolism : Cytosol, Intestine, Small, Microsomes, Liver.
- chemical , pharmacology : Hesperidin.
- ultrastructure : Intestine, Small.
- Animals, Biological Transport, Caco-2 Cells, Cell Line, Tumor, Humans, Liver Neoplasms, Experimental, Mice, Stereoisomerism, Structure-Activity Relationship, Transfection.
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.
DOI: 10.1021/jf1008617
PubMed: 20441166
Affiliations:
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Le document en format XML
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Walter.Brand@WUR.nl</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Toxicology, Wageningen University, Tuinlaan 5, PO Box 8000, 6703 HE Wageningen</wicri:regionArea><orgName type="university">Université de Wageningue</orgName><placeName><settlement type="city">Wageningue</settlement><region nuts="2">Gueldre (province)</region></placeName></affiliation></author><author><name sortKey="Shao, Jia" sort="Shao, Jia" uniqKey="Shao J" first="Jia" last="Shao">Jia Shao</name></author><author><name sortKey="Hoek Van Den Hil, Elisabeth F" sort="Hoek Van Den Hil, Elisabeth F" uniqKey="Hoek Van Den Hil E" first="Elisabeth F" last="Hoek-Van Den Hil">Elisabeth F. Hoek-Van Den Hil</name></author><author><name sortKey="Van Elk, Kathelijn N" sort="Van Elk, Kathelijn N" uniqKey="Van Elk K" first="Kathelijn N" last="Van Elk">Kathelijn N. Van Elk</name></author><author><name sortKey="Spenkelink, Bert" sort="Spenkelink, Bert" uniqKey="Spenkelink B" first="Bert" last="Spenkelink">Bert Spenkelink</name></author><author><name sortKey="De Haan, Laura H J" sort="De Haan, Laura H J" uniqKey="De Haan L" first="Laura H J" last="De Haan">Laura H J. De Haan</name></author><author><name sortKey="Rein, Maarit J" sort="Rein, Maarit J" uniqKey="Rein M" first="Maarit J" last="Rein">Maarit J. Rein</name></author><author><name sortKey="Dionisi, Fabiola" sort="Dionisi, Fabiola" uniqKey="Dionisi F" first="Fabiola" last="Dionisi">Fabiola Dionisi</name></author><author><name sortKey="Williamson, Gary" sort="Williamson, Gary" uniqKey="Williamson G" first="Gary" last="Williamson">Gary Williamson</name></author><author><name sortKey="Van Bladeren, Peter J" sort="Van Bladeren, Peter J" uniqKey="Van Bladeren P" first="Peter J" last="Van Bladeren">Peter J. Van Bladeren</name></author><author><name sortKey="Rietjens, Ivonne M C M" sort="Rietjens, Ivonne M C M" uniqKey="Rietjens I" first="Ivonne M C M" last="Rietjens">Ivonne M C M. Rietjens</name></author></analytic><series><title level="j">Journal of agricultural and food chemistry</title><idno type="eISSN">1520-5118</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Biological Transport</term><term>Caco-2 Cells</term><term>Cell Line, Tumor</term><term>Citrus sinensis (chemistry)</term><term>Cytosol (metabolism)</term><term>Fruit (chemistry)</term><term>Gene Expression (drug effects)</term><term>Glucuronides (metabolism)</term><term>Hesperidin (chemistry)</term><term>Hesperidin (metabolism)</term><term>Hesperidin (pharmacology)</term><term>Humans</term><term>Intestine, Small (metabolism)</term><term>Intestine, Small (ultrastructure)</term><term>Liver Neoplasms, Experimental</term><term>Mice</term><term>Microsomes, Liver (metabolism)</term><term>Response Elements (genetics)</term><term>Stereoisomerism</term><term>Structure-Activity Relationship</term><term>Sulfonic Acids (metabolism)</term><term>Transfection</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Hesperidin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glucuronides</term><term>Hesperidin</term><term>Sulfonic Acids</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Citrus sinensis</term><term>Fruit</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Gene Expression</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Response Elements</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cytosol</term><term>Intestine, Small</term><term>Microsomes, Liver</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Hesperidin</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Intestine, Small</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biological Transport</term><term>Caco-2 Cells</term><term>Cell Line, Tumor</term><term>Humans</term><term>Liver Neoplasms, Experimental</term><term>Mice</term><term>Stereoisomerism</term><term>Structure-Activity Relationship</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li></country><region><li>Gueldre (province)</li></region><settlement><li>Wageningue</li></settlement><orgName><li>Université de Wageningue</li></orgName></list><tree><noCountry><name sortKey="De Haan, Laura H J" sort="De Haan, Laura H J" uniqKey="De Haan L" first="Laura H J" last="De Haan">Laura H J. De Haan</name><name sortKey="Dionisi, Fabiola" sort="Dionisi, Fabiola" uniqKey="Dionisi F" first="Fabiola" last="Dionisi">Fabiola Dionisi</name><name sortKey="Hoek Van Den Hil, Elisabeth F" sort="Hoek Van Den Hil, Elisabeth F" uniqKey="Hoek Van Den Hil E" first="Elisabeth F" last="Hoek-Van Den Hil">Elisabeth F. Hoek-Van Den Hil</name><name sortKey="Rein, Maarit J" sort="Rein, Maarit J" uniqKey="Rein M" first="Maarit J" last="Rein">Maarit J. Rein</name><name sortKey="Rietjens, Ivonne M C M" sort="Rietjens, Ivonne M C M" uniqKey="Rietjens I" first="Ivonne M C M" last="Rietjens">Ivonne M C M. Rietjens</name><name sortKey="Shao, Jia" sort="Shao, Jia" uniqKey="Shao J" first="Jia" last="Shao">Jia Shao</name><name sortKey="Spenkelink, Bert" sort="Spenkelink, Bert" uniqKey="Spenkelink B" first="Bert" last="Spenkelink">Bert Spenkelink</name><name sortKey="Van Bladeren, Peter J" sort="Van Bladeren, Peter J" uniqKey="Van Bladeren P" first="Peter J" last="Van Bladeren">Peter J. Van Bladeren</name><name sortKey="Van Elk, Kathelijn N" sort="Van Elk, Kathelijn N" uniqKey="Van Elk K" first="Kathelijn N" last="Van Elk">Kathelijn N. Van Elk</name><name sortKey="Williamson, Gary" sort="Williamson, Gary" uniqKey="Williamson G" first="Gary" last="Williamson">Gary Williamson</name></noCountry><country name="Pays-Bas"><region name="Gueldre (province)"><name sortKey="Brand, Walter" sort="Brand, Walter" uniqKey="Brand W" first="Walter" last="Brand">Walter Brand</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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