Inhibition mechanisms of α-glucosidase by eight catechins: Kinetic, molecular docking, and surface plasmon resonance analysis.

Abstract

α-Glucosidase is considered to be one of the effective targets for the treatment of type 2 diabetes. This study examined the inhibitory mechanisms of eight catechins on α-glucosidase, including both the free forms (C, EC, GC, EGC) and esterified forms (CG, ECG, GCG, EGCG). Enzyme kinetics and molecular docking studies demonstrated that catechins primarily inhibit α-glucosidase by binding through hydrogen bonds and hydrophobic interactions, with esterified catechins exhibiting stronger inhibitory effects. The structural changes of the proteins following binding were further explored using fluorescence spectroscopy and atomic force microscopy (AFM). Fluorescence spectroscopy revealed that catechins altered the microenvironment around the fluorescent amino acids within the enzyme (such as tyrosine and tryptophan), resulting in slight unfolding of the protein structure. AFM further confirmed that catechin binding to α-glucosidase induced protein aggregation, with esterified catechins exhibiting a more pronounced effect. All of the above findings were based on static model studies. Moreover, the binding kinetics of catechins with α-glucosidase were innovatively investigated using surface plasmon resonance (SPR), revealing that esterified catechins bound more rapidly and displayed higher affinity. The presence of the gallate group in esterified catechins was identified as crucial for their binding to α-glucosidase, resulting in a more significant inhibitory effect. These findings suggested that dietary intake of catechins, especially esterified form, may more effectively inhibit the activity of α-glucosidase.