Flavonoid glycosides are not transported by the human Na ⁺/glucose transporter when expressed in Xenopus laevis oocytes, but effectively inhibit electrogenic glucose uptake

There is controversy as to whether intestinal absorption of glycosylated flavonoids, and particularly quercetin glycosides, involves their uptake in intact form via the human sodium-coupled glucose transporter hSGLT1. We here describe studies using Xenopus oocytes that express hSGLT1 and the two-electrode voltage clamp technique to determine the transport characteristics of a variety of flavonoids carrying glucose residues at different positions as well as of their aglycones (altogether 27 compounds). Neither quercetin, luteolin, apigenin, naringenin, pelarginidin, daidzein, or genistein, nor any of their glycosylated derivatives generated significant transport currents. However, the inward current evoked by 1 mM of the hSGLT1 substrate α-methyl-D- glucopyranoside was potently reduced by the simultaneous application of not only various flavonoid glycosides but also by some aglycones. The inhibitory potency remained unchanged when the attached glucose was replaced by galactose, suggesting that these residues may bind to SGLT1. Kinetic analysis by Dixon plots revealed inhibition of competitive type with high affinities, particularly when the glucose was attached to the position 4′ of the aromatic ring of the flavonoids. The affinities became lower when the glucose was attached to a different position. Unexpectedly, the aglycone form of luteolin also inhibited the transport competitively with high affinity. These data show that hSGLT1 does not transport any of the flavonoids and seems therefore not involved in their intestinal absorption. However, not only glycosylated but also a few nonglycosylated flavonoids show a structure-dependent capability for effective inhibition of SGLT1.