Dietary natural products as inhibitors of α-amylase and α-glucosidase: An updated review of ligand-receptor correlations validated by docking studies

Abstract

A therapeutic strategy to treat Type 2 diabetes mellitus (T2D) is focused on controlling postprandial glucose levels by inhibiting α-amylase and α-glucosidase. These enzymes are essential to convert assimilable carbohydrates into glucose. Nutraceuticals contained in plant foods exert inhibitory properties on these enzymes, which are comparable to standard antidiabetic drugs. The present review aimed to compilate and discuss the hypoglycemic effectiveness of selected nutraceuticals by contrasting docking analysis and available experimental data. The binding energies for α-amylase and α-glucosidase inhibitors considered in our compilation were in the range from −19.19 to −5.20 kcal/mol and −14.50 to −4.35 kcal/mol, respectively. In vivo and in vitro experimental evidence, indicates that small molecules (mainly polyphenols) and biopeptides can be initially predicted as natural inhibitors of α-amylase and α-glucosidase by molecular docking. Detailed analysis sustains that the active site of α-amylase may experience more extensive ligand interactions at neighboring subsites stabilized under higher binding energies than α-glucosidase. Interestingly, higher binding energy is proportional to the ligand molecular weight for α-amylase with a moderate Pearson correlation coefficient of 0.5514. Derived from the analyzed scientific literature, recent findings suggest that several molecular properties and forces contribute to ligand stabilization in the active site of both enzymes. Despite our review provides concrete evidence on the use of dietary natural products as potential inhibitors of α-amylase and α-glucosidase, doses, toxicity, and pharmacokinetics data should endorse the reliability of in silico approaches to envision compound effectiveness.