Natural Sweetener, Glycyrrhetinic Acid 3-O-Mono-beta-d-glucuronide, for Postprandial Hyperglycemia Management

This study examines the inhibitory effects of a range of sweeteners on α-glucosidase. Our findings revealed that only one natural sweetener, namely, glycyrrhetinic acid 3-O-mono-beta-d-glucuronide (GAMG), derived from licorice, exhibited a mixed-type inhibition against α-glucosidase with a IC50 value of 0.73 ± 0.05 mg/mL. The fluorescence intensity of α-glucosidase was quenched by GAMG in the formation of an α-glucosidase–GAMG complex. GAMG has been shown to induce conformational changes in α-glucosidase, likely through hydrogen bonding, van der Waals force, and alkyl–alkyl interactions with amino acid residues, including Arg 281, Leu 283, Trp 376, Asp 404, Asp 443, Trp 481, Asp 518, Phe 525, Ala 555, and Asp 616. Additional animal validation experiments demonstrated that GAMG slowed starch digestion, thereby attenuating the postprandial glycemic response. Taken together, these findings provide evidence that GAMG is a natural sweetener with potent inhibitory activity that selectively targets α-glucosidase. This study supports the use of GAMG as a natural sweetener, which holds a high biological value and may be beneficial for managing postprandial hyperglycemia.