In Vitro Inhibitory Effects of Polyphenols from Flos sophorae immaturus on α-Glucosidase: Action Mechanism, Isothermal Titration Calorimetry and Molecular Docking Analysis.

Abstract

Flos sophorae immaturus (FSI) is considered to be a natural hypoglycemic product with the potential for a-glucosidase inhibitory activity. In this work, the polyphenols with α-glucosidase inhibition in FSI were identified, and then their potential mechanisms were investigated by omission assay, interaction, type of inhibition, fluorescence spectroscopy, circular dichroism, isothermal titration calorimetry and molecular docking analysis. The results showed that five polyphenols, namely rutin, quercetin, hyperoside, quercitrin and kaempferol, were identified as a-glucosidase inhibitors with IC50 values of 57, 0.21, 12.77, 25.37 and 0.55 mg/mL, respectively. Quercetin plays a considerable a-glucosidase inhibition role in FSI. Furthermore, the combination of quercetin with kaempferol generated a subadditive effect, and the combination of quercetin with rutin, hyperoside and quercitrin exhibited an interference effect. The results of inhibition kinetics, fluorescence spectroscopy, isothermal titration calorimetry and molecular docking analysis showed that the five polyphenols were mixed inhibitors and significantly burst the fluorescence intensity of α-glucosidase. Moreover, the isothermal titration calorimetry and molecular docking analysis showed that the binding to α-glucosidase was a spontaneous heat-trapping process, with hydrophobic interactions and hydrogen bonding being the key drivers. In general, rutin, quercetin, hyperoside, quercitrin and kaempferol in FSI are potential α-glucosidase inhibitors.