The effect of co‐administered flavonoids on the metabolism of hesperetin and the disposition of its metabolites in Caco‐2 cell monolayers
- 7 June 2010
- journal article
- research article
- Published by Wiley in Molecular Nutrition & Food Research
- Vol. 54 (6), 851-860
- https://doi.org/10.1002/mnfr.200900183
Abstract
Metabolism by phase II enzymes and transport from intestinal cells back into the lumen by ATP binding cassette (ABC) transporters limits the bioavailability of the flavanone hesperetin, the aglycone of hesperidin. This study investigates to what extent other flavonoids modulate the metabolism and transport of hesperetin by characterizing the effect of co-administrating a series of flavonoids using Caco-2 cell monolayers in a two-compartment transwell system. Flavonoids may interfere with hesperetin metabolism and can also inhibit the apically located ABC transporter breast cancer resistance protein (ABCG2) which was previously shown to be responsible for the apical transport of hesperetin metabolites. Co-exposure of Caco-2 cell monolayers to hesperetin with specific flavonoids reduced the ratio of apical efflux to basolateral transport of hesperetin metabolites, and in some cases, also reduced the amount of hesperetin metabolites detected extracellularly. As intracellular accumulation of hesperetin metabolites did not account for this decrease, inhibition of metabolism of hesperetin is likely the underlying mechanism for the reduced metabolite formation and excretion. In spite of the reduction in metabolism the amount of hesperetin metabolites transported to the basolateral side significantly increased upon co-exposure with specific flavonoids and therefore co-administration of specific flavonoids could be a strategy to improve the bioavailability of hesperetin.Keywords
Funding Information
- Nestle Research Center
This publication has 44 references indexed in Scilit:
- Metabolism and Transport of the Citrus Flavonoid Hesperetin in Caco-2 Cell MonolayersDrug Metabolism and Disposition, 2008
- Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact ratsJournal of Applied Physiology, 2008
- Flavanone plasma pharmacokinetics from blood orange juice in human subjectsBritish Journal of Nutrition, 2007
- Natural polyphenol disposition via coupled metabolic pathwaysExpert Opinion on Drug Metabolism & Toxicology, 2007
- Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjectsEuropean Journal of Clinical Nutrition, 2006
- Modulation of the age‐related nuclear factor‐κB (NF‐κB) pathway by hesperetinAging Cell, 2006
- Breast Cancer Resistance Protein (Bcrp1/Abcg2) Limits Net Intestinal Uptake of Quercetin in Rats by Facilitating Apical Efflux of GlucuronidesMolecular Pharmacology, 2005
- Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juiceEuropean Journal of Clinical Nutrition, 2003
- Flavanones, chalcones and dihydrochalcones - nature, occurrence and dietary burdenJournal of the Science of Food and Agriculture, 2000
- Flavanone absorption after naringin, hesperidin, and citrus administration*Clinical Pharmacology & Therapeutics, 1996