Noncompetitive Inhibition of Sodium-Glucose Cotransporter by Unripe Apple Polyphenol Extract in the Mouse Small Intestine.

The health benefits of apple polyphenols are well-documented. Phlorizin (Pz), an apple-derived polyphenol, is a known inhibitor of sodium-glucose cotransporters (SGLTs); however, the effects of other apple constituents on SGLTs remain unclear. In this study, we examined the inhibitory effects of an unripe apple polyphenol extract, ApplePhenon® (AP), and its constituents-including Pz, phloretin, procyanidins B1 and B2, chlorogenic acid, gallic acid, catechin, epicatechin, epigallocatechin gallate, and quercetin-on SGLTs using the Ussing chamber in mouse small intestinal mucosa. AP exhibited noncompetitive inhibition of glucose-induced short-circuit current (Isc), reflecting electrogenic Na+ transport via SGLTs (apparent Ki = 22.23 ± 3.06 μg·mL-1). A similar inhibitory effect was observed in the case of Pz (Ki = 1.88 ± 0.32 μg·mL-1), phloretin (Ki = 18.82 ± 3.52 μg·mL-1), and quercetin (Ki = 220.9 ± 3.52 μg·mL-1) but not in other components. Based on the total Pz content of 6.2%, 86.0% of the inhibitory effect can be attributed to Pz. Although Pz is known to inhibit SGLT1 competitively, AP and its constituents, including Pz, phloretin, and quercetin, showed noncompetitive inhibition in this study. These findings warrant further investigation into the mechanisms underlying SGLT inhibition by AP.