In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

Abstract

Human pancreatic α-amylase (HPA), situated at the apex of the starch digestion hierarchy, is an attractive therapeutic approach to precisely regulate blood glucose levels, thereby efficiently managing diabetes. Polyphenols offer a natural and multifaceted approach to moderate postprandial sugar spikes, with their slight modulation in carbohydrate digestion and potential secondary benefits, such as antioxidant and antiinflammatory effects. Taking into consideration the unfavorable side effects of currently available commercial medications, we aimed to study a library of polyphenols attributed to their remarkable antidiabetic properties and screened the most potent HPA inhibitor via a comprehensive in silico study encompassing molecular docking, molecular mechanics with generalized Born and surface area solvation (MM/GBSA) calculation, molecular dynamics (MD) simulation, density functional theory (DFT) study, and pharmacokinetic properties followed by an in vitro assay. Significant hydrogen bonding with the catalytic triad residues of HPA, prominent MM/ GBSA binding energy of −27.03 kcal/mol, and the stable nature of the protein−ligand complex with regard to 100 ns MD simulation screened quercetin as the best HPA inhibitor. Additionally, quercetin showed strong reactivity in the substrate-binding pocket of HPA and exhibited favorable pharmacokinetic properties with a considerable inhibitory concentration (IC 50 ) of 57.37 ± 0.9 μg/mL against α-amylase. This study holds prospects for HPA inhibition and suggests quercetin as an approach to therapy for diabetes; however, it is imperative to conduct further research.

Assessment of Quercetin Antiemetic Properties: In Vivo and In Silico Investigations on Receptor Binding Affinity and Synergistic Effects

“…Typically, the bioavailability of QUA is seen to be rather low and exhibits considerable inter-individual variability, despite a limited understanding of the underlying processes [ 64 ]. QUA, when administered in vivo to rats and pigs, has been seen to result in the presence of relatively low concentrations (ranging from picomolar to nanomolar levels) in brain tissue [ 65 ]. One crucial concern about the possible in vivo use of QUA is its ability to traverse the blood–brain barrier (BBB) [ 66 ].…”