Cellular uptake of dietary flavonoid quercetin 4 '-beta-glucoside by sodium-dependent glucose transporter SGLT1

Although it has been suggested that the intestinal glucose transporter may actively absorb dietary flavonoid glucosides, there is a lack of direct evi dence for their transport by this system. In fact, our previous studies wit h the human Caco-2 cell model of intestinal absorption demonstrated that a major dietary flavonoid, quercetin 4'-beta-glucoside, is effluxed by apical ly expressed multidrug resistance-associated protein-2, potentially masking evidence for active absorption. The objective of this study was to test th e hypothesis that quercetin 4'-beta-glucoside is a substrate for the intest inal sodium-dependent D-glucose cotransporter SGLT1, Cellular uptake of que rcetin 4'-beta-glucoside was examined with Caco-2 cells and SGLT1 stably tr ansfected Chinese hamster ovary cells (G6D3 cells). Although quercetin 4'-b eta-glucoside is not absorbed across Caco-2 cell monolayers, examination of the cells by indirect fluorescent microscopy as well as by HPLC analysis o f cellular content revealed cellular accumulation of this glucoside after a pical loading. Consistent with previous observations, the accumulation of q uercetin 4'-beta-glucoside in both Caco-2 and G6D3 cells was markedly enhan ced in the presence of multidrug resistance-associated protein inhibition. Uptake of quercetin 4'-beta-glucoside was greater in SGLT1-transfected cell s than in parental Chinese hamster ovary cells. Uptake of the glucoside by Caco-2 and G6D3 cells was sodium-dependent and was inhibited by the monoval ent ionophore nystatin. In both Caco-2 and G6D3 cells, quercetin 4'-beta-gl ucoside uptake was inhibited by 30 mM glucose and 0.5 mM phloridzin. These results demonstrate for the first lime that quercetin 4'-beta-glucoside is transported by SGLT1 across the apical membrane of enterocytes.