Molecular mechanisms of the naringin low uptake by intestinal Caco-2 cells

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 (Papp = 8.1 ± 0.9×10–8 cm/s). In the presence of verapamil, a specific inhibitor of P‐glycoprotein, cellular uptake was increased by almost threefold after 5 min, and Papp 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.