Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels.
Identifieur interne : 000183 ( Main/Exploration ); précédent : 000182; suivant : 000184Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels.
Auteurs : Juan Antonio Giménez-Bastida [Espagne] ; Antonio González-Sarrías [Espagne] ; Fernando Vallejo [Espagne] ; Juan Carlos Espín [Espagne] ; Francisco A. Tomás-Barberán [Espagne]Source :
- Food & function [ 2042-650X ] ; 2016.
English descriptors
- KwdEn :
- Aorta (cytology), Cell Line, Cell Movement (drug effects), Citrus sinensis (chemistry), Endothelial Cells (physiology), Fruit (chemistry), Glucuronides (pharmacology), Hesperidin (metabolism), Hesperidin (pharmacology), Humans, Inflammation, Interleukin-6 (metabolism), Interleukin-8 (metabolism), Plasminogen Activator Inhibitor 1 (analysis), Sulfates (pharmacology), Tumor Necrosis Factor-alpha (antagonists & inhibitors), Tumor Necrosis Factor-alpha (pharmacology).
- MESH :
- chemical , analysis : Plasminogen Activator Inhibitor 1.
- chemical , antagonists & inhibitors : Tumor Necrosis Factor-alpha.
- chemical , metabolism : Hesperidin, Interleukin-6, Interleukin-8.
- chemical , pharmacology : Glucuronides, Hesperidin, Sulfates, Tumor Necrosis Factor-alpha.
- chemistry : Citrus sinensis, Fruit.
- cytology : Aorta.
- drug effects : Cell Movement.
- physiology : Endothelial Cells.
- Cell Line, Humans, Inflammation.
Abstract
Epidemiological, clinical and preclinical studies have reported the protection offered by citrus consumption, mainly orange, against cardiovascular diseases, which is primarily mediated by the antiatherogenic and vasculoprotective effects of the flavanone hesperetin-7-O-rutinoside (hesperidin). However, flavanone aglycones or glycosides are not present in the bloodstream but their derived phase-II metabolites could be the actual bioactive molecules. To date, only a few studies have explored the effects of circulating hesperetin-derived metabolites (glucuronides and sulfates) on endothelial cells. Herein, we describe for the first time the effects of hesperetin 3'-O-glucuronide, hesperetin 7-O-glucuronide, hesperetin 3'-O-sulfate, hesperetin 7-O-sulfate and hesperetin on human aortic endothelial cell (HAEC) migration upon pro-inflammatory stimuli as an essential step to angiogenesis. Hesperetin and its derived metabolites, at physiologically relevant concentrations (1-10 μM), significantly attenuated cell migration in the presence of the pro-inflammatory cytokine TNF-α (50 ng mL(-1)), which was accompanied and perhaps mediated by a significant decrease in the levels of the thrombogenic plasminogen activator inhibitor-1 (PAI-1). However, hesperetin metabolites did not counteract the TNF-α-induced production of pro-inflammatory interleukin-6 (IL-6) and IL-8. We also study here for the first time, the metabolism of hesperetin and its derived metabolites by HAEC with and without a pro-inflammatory stimulus. All these results reinforce the concept according to which circulating phase-II hesperetin metabolites are critical molecules contributing to the cardioprotective effects upon consumption of citrus fruits such as orange.
DOI: 10.1039/c5fo00771b
PubMed: 26456097
Affiliations:
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Le document en format XML
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Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain. agsarrias@cebas.csic.es.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia</wicri:regionArea><wicri:noRegion>Murcia</wicri:noRegion></affiliation></author><author><name sortKey="Gonzalez Sarrias, Antonio" sort="Gonzalez Sarrias, Antonio" uniqKey="Gonzalez Sarrias A" first="Antonio" last="González-Sarrías">Antonio González-Sarrías</name><affiliation wicri:level="1"><nlm:affiliation>Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain. agsarrias@cebas.csic.es.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia</wicri:regionArea><wicri:noRegion>Murcia</wicri:noRegion></affiliation></author><author><name sortKey="Vallejo, Fernando" sort="Vallejo, Fernando" uniqKey="Vallejo F" first="Fernando" last="Vallejo">Fernando Vallejo</name><affiliation wicri:level="1"><nlm:affiliation>Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain. agsarrias@cebas.csic.es.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia</wicri:regionArea><wicri:noRegion>Murcia</wicri:noRegion></affiliation></author><author><name sortKey="Espin, Juan Carlos" sort="Espin, Juan Carlos" uniqKey="Espin J" first="Juan Carlos" last="Espín">Juan Carlos Espín</name><affiliation wicri:level="1"><nlm:affiliation>Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain. agsarrias@cebas.csic.es.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia</wicri:regionArea><wicri:noRegion>Murcia</wicri:noRegion></affiliation></author><author><name sortKey="Tomas Barberan, Francisco A" sort="Tomas Barberan, Francisco A" uniqKey="Tomas Barberan F" first="Francisco A" last="Tomás-Barberán">Francisco A. Tomás-Barberán</name><affiliation wicri:level="1"><nlm:affiliation>Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain. agsarrias@cebas.csic.es.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia</wicri:regionArea><wicri:noRegion>Murcia</wicri:noRegion></affiliation></author></analytic><series><title level="j">Food & function</title><idno type="eISSN">2042-650X</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aorta (cytology)</term><term>Cell Line</term><term>Cell Movement (drug effects)</term><term>Citrus sinensis (chemistry)</term><term>Endothelial Cells (physiology)</term><term>Fruit (chemistry)</term><term>Glucuronides (pharmacology)</term><term>Hesperidin (metabolism)</term><term>Hesperidin (pharmacology)</term><term>Humans</term><term>Inflammation</term><term>Interleukin-6 (metabolism)</term><term>Interleukin-8 (metabolism)</term><term>Plasminogen Activator Inhibitor 1 (analysis)</term><term>Sulfates (pharmacology)</term><term>Tumor Necrosis Factor-alpha (antagonists & inhibitors)</term><term>Tumor Necrosis Factor-alpha (pharmacology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Plasminogen Activator Inhibitor 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Tumor Necrosis Factor-alpha</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Hesperidin</term><term>Interleukin-6</term><term>Interleukin-8</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Glucuronides</term><term>Hesperidin</term><term>Sulfates</term><term>Tumor Necrosis Factor-alpha</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Citrus sinensis</term><term>Fruit</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Aorta</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Movement</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Endothelial Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Humans</term><term>Inflammation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Epidemiological, clinical and preclinical studies have reported the protection offered by citrus consumption, mainly orange, against cardiovascular diseases, which is primarily mediated by the antiatherogenic and vasculoprotective effects of the flavanone hesperetin-7-O-rutinoside (hesperidin). However, flavanone aglycones or glycosides are not present in the bloodstream but their derived phase-II metabolites could be the actual bioactive molecules. To date, only a few studies have explored the effects of circulating hesperetin-derived metabolites (glucuronides and sulfates) on endothelial cells. Herein, we describe for the first time the effects of hesperetin 3'-O-glucuronide, hesperetin 7-O-glucuronide, hesperetin 3'-O-sulfate, hesperetin 7-O-sulfate and hesperetin on human aortic endothelial cell (HAEC) migration upon pro-inflammatory stimuli as an essential step to angiogenesis. Hesperetin and its derived metabolites, at physiologically relevant concentrations (1-10 μM), significantly attenuated cell migration in the presence of the pro-inflammatory cytokine TNF-α (50 ng mL(-1)), which was accompanied and perhaps mediated by a significant decrease in the levels of the thrombogenic plasminogen activator inhibitor-1 (PAI-1). However, hesperetin metabolites did not counteract the TNF-α-induced production of pro-inflammatory interleukin-6 (IL-6) and IL-8. We also study here for the first time, the metabolism of hesperetin and its derived metabolites by HAEC with and without a pro-inflammatory stimulus. All these results reinforce the concept according to which circulating phase-II hesperetin metabolites are critical molecules contributing to the cardioprotective effects upon consumption of citrus fruits such as orange.</div></front></TEI><affiliations><list><country><li>Espagne</li></country></list><tree><country name="Espagne"><noRegion><name sortKey="Gimenez Bastida, Juan Antonio" sort="Gimenez Bastida, Juan Antonio" uniqKey="Gimenez Bastida J" first="Juan Antonio" last="Giménez-Bastida">Juan Antonio Giménez-Bastida</name></noRegion><name sortKey="Espin, Juan Carlos" sort="Espin, Juan Carlos" uniqKey="Espin J" first="Juan Carlos" last="Espín">Juan Carlos Espín</name><name sortKey="Gonzalez Sarrias, Antonio" sort="Gonzalez Sarrias, Antonio" uniqKey="Gonzalez Sarrias A" first="Antonio" last="González-Sarrías">Antonio González-Sarrías</name><name sortKey="Tomas Barberan, Francisco A" sort="Tomas Barberan, Francisco A" uniqKey="Tomas Barberan F" first="Francisco A" last="Tomás-Barberán">Francisco A. Tomás-Barberán</name><name sortKey="Vallejo, Fernando" sort="Vallejo, Fernando" uniqKey="Vallejo F" first="Fernando" last="Vallejo">Fernando Vallejo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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