Sodium-dependent glucose transporter 1 and glucose transporter 2 mediate intestinal transport of quercetrin in Caco-2 cells

Background: The role of glucose transporters in the transport of flavonoids remains ambiguous.

Objective: In this study, we examined whether quercitrin would be absorbed intactly in modeled Caco-2 cells, as well as determined the involvement of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in its transmembrane transport.

Design: The first experiment was conducted to examine the uptake of quercitrin into Caco-2 cells 24 h after they were seeded and the second experiment was conducted to determine the transport across the apical and basolateral membrane of Caco-2 cells after they were cultured for 21 days in a Millicell system. Quercitrin was administered at 3, 9, or 18 μg/mL; and the time points of sampling were 30, 60, 90, 120, and 150 min.

Results: In the uptake experiment, the highest intracellular quercitrin concentration was observed in the cells treated with 18 μg/mL quercitrin at 60 min, with a bell-shaped kinetic curve. Quercetin, isorhamnetin, and tamarixetin were detected inside the cells, particularly when treated with a high dose. In the transport experiment, quercitrin was transported from the apical to basolateral side and vice versa; its concentrations depended on dose, time, and transport direction (P < 0.0001). Only trace amounts of isorhamnetin and tamarixetin were detected in the apical chamber when quercitrin was added to the basolateral chamber. Phloridzin and phloretin, potent inhibitors of SGLT1 and GLUT2, respectively, significantly diminished quercitrin transport from the apical to basolateral side; and phloretin had a greater inhibitory effect compared to phloridzin.

Conclusion: Our results demonstrate that quercitrin is absorbed intactly and then effluxed out of Caco-2 cells through both apical and basolateral membranes probably via SGLT1 and GLUT2.