Hydroxylated soy isoflavones exhibit anti-diabetic properties via the inhibition of alpha-glucosidase and sodium-dependent glucose transporter SGLT1

Background and objectives: The prevalence of type 2 diabetes (T2DM) is increasing globally. Controlling postprandial hyperglycemia by dietary means is crucial for the prevention of T2DM. Blood glucose levels are determined by various factors including food constituents and food matrix, carbohydrate hydrolyzing enzymes (e.g. alpha-amylase, alpha-glucosidase), glucose transporters and hormones. Although there is some evidence that soy-derived isoflavones such as genistein and glycitein may exhibit antidiabetic properties, little is known to what extent their corresponding hydroxylated metabolites including 8-hydroxy genistein (8OHGen) and 8-hydroxy glycitein (8OHGly) may affect glucose metabolism. Hydroxylation of isoflavones mainly occurs via food fermentation as well as phase I metabolism in the liver. Materials and Methods: Alpha-amylase and alpha-glucosidase inhibitory activity of a soy isoflavone extract rich in 8OHGen (34% of total isoflavones) and 8OHGly (9 % of total isoflavones) was determined in vitro by applying a disc and spectrophotometric assay, respectively. Acarbose was used as a positive control. By mounting Caco2 cells on Ussing chambers we determined the effect of the soy isoflavone extract on sodium-dependent glucose uptake via the glucose transporter SGLT1. Phlorizin was used as a positive control. Results: In vitro alpha-amylase activity was not changed due the soy isoflavone extract. However, we observed a concentration-dependent inhibitory effect of the soy isoflavone extract on alpha-glucosidase activity with statistical significance at a concentration of 10 µg/ml. The IC50 value of the isoflavone extract was estimated to be 78.6 µg/ml. Compared to the positive control acarbose (IC50 = 493 µg/ml) the soy isoflavone extract was six times more potent in inhibiting alpha-glucosidase. Adding the hydroxy-isoflavone-rich extract at a concentration of 1 µg/ml to Caco2 cells substantially lowered the glucose-induced short circuit current from 9.24 ± 1.73 to 3.63 ± 0.70 µA/cm2 in the Ussing chamber experiments. This represents a SGLT1 inhibition of approximately 60%. Conclusion: Our data indicate that a soy isoflavone extract rich in 8OHGen and 8OHGly exhibits potent antidiabetic properties by inhibiting alpha-glucosidase and SGLT1 in vitro. Present in vitro data should be verified in appropriate in vivo studies including laboratory rodents and humans.