title: Molecular mechanisms of the naringin low uptake by intestinal Caco-2 cells.
abstract: Naringin, the main flavanone of grapefruit, was reported to display numerous biological effects: antioxidant, hypocholesteremic, anti-atherogenic and favoring drug absorption. Naringin absorption mechanisms were studied in Caco-2 cells (TC7 clone). We investigated the possible involvement of several membrane transporters implicated in polyphenolic compounds intestinal transport (sodium-dependent glucose transporter 1, monocarboxylate transporter, multidrug-associated resistance proteins 1 and 2, and P-glycoprotein). Naringin was poorly absorbed by Caco-2 cells, according to its low value of apparent permeability coefficient (P(app) = 8.1 +/- 0.9 x 10(-8) cm/s). In the presence of verapamil, a specific inhibitor of P-glycoprotein, cellular uptake was increased by almost threefold after 5 min, and P(app) was doubled after 30 min. Our results indicated the involvement of P-glycoprotein, an ATP-driven efflux pump, capable of transporting naringin from the Caco-2 cell to the apical side. This phenomenon could explain, at least in part, the low absorption of this flavanone at the upper intestinal level.
authors.affiliation: UMR U-476 INSERM/U-1260 INRA, Faculté de Médecine, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Tourniaire
authors.forename: Meryl
authors.initials: M
authors.lastname: Hassan
authors.forename: Marc
authors.initials: M
authors.lastname: André
authors.forename: Odette
authors.initials: O
authors.lastname: Ghiringhelli
authors.forename: Christian
authors.initials: C
authors.lastname: Alquier
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Amiot
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D044950:Flavanones / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D010539:Permeability; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D044950:Flavanones; D014700:Verapamil; C005274:naringin