Inhibition mechanism of different structural polyphenols against α-amylase studied by solid-state NMR and molecular docking

Polyphenol has the considerable effects for inhibition of digestive enzymes, however, inhibition mechanism of molecular size-dependent polyphenols on enzyme activity is still lacking. Herein, inhibition effect and binding interactions of three different structural polyphenols (catechol, quercetin and hesperidin) on alpha-amylase were studied. Inhibition assays proved that polyphenols significantly inhibited alpha-amylase and their effects were increased with their molecular sizes. Hesperidin showed the highest inhibition ability of alpha-amylase, which was determined as IC50 = 0.43 mg/mL. Fluorescence and FT-IR spectroscopy proved that inter-molecular interactions between polyphenols and alpha-amylase occurred through non-covalent bonds. Besides, the secondary structure of alpha-amylase was obviously changed after binding with polyphenols. Inter-molecular interactions were investigated using solid-state NMR and molecular docking. Findings proved that hydrogen bonds and it-it stacking interactions were the mainly inter-molecular interactions. We hope this contribution could provide a theoretical basis for developing some digestive enzyme inhibitors from natural polyphenols.