Astragalin Exerted Hypoglycemic Effect by Both Inhibiting α-Glucosidase and Modulating AMPK Signaling Pathway

The hypoglycemic activity of mulberry leaf polyphenols has been widely studied, while its mechanism of action needs further elucidation.

The inhibitory activity mechanism of astragalin on α-glucosidase was investigated with a combination of multispectroscopic techniques and molecular docking. The hypoglycemic pathway was further revealed with a high-glucose human hepatocellular carcinomas (HepG2) cell model.

The results indicated that astragalin inhibited α-glucosidase with IC₅₀ of 154.5 µM, which was the highest in potency among the main polyphenols from mulberry leaves. Astragalin could bind to α-glucosidase with a single inhibition site and quench its endofluorescence with a static quenching mechanism. Astragalin changed the secondary structure of α-glucosidase, and the decreased α-helix content, representing the un-folding conformation, resulted in the decreased activity. The molecular docking further indicated that two sustainable hydrogen bonds were generated between astragalin and α-glucosidase residue Ser-88 and Tyr-133. The main driving forces to form the astragalin-α-glucosidase complex were the van der Waals force and hydrogen bond. Astragalin at a concentration of 80 µg/mL obtained the best hypoglycemic effect by activating the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway.

This study provides new insights into the potential utilization of astragalin-rich foods in the improvement of diabetes mellitus.