In-Silico Analysis and Antidiabetic Effect of α-Amylase and α-Glucosidase Inhibitory Peptides from Lupin Protein Hydrolysate: Enzyme-Peptide Interaction Study Using Molecular Docking Approach

The use of natural ingredients for managing diabetes is becoming more popular in recent times due to the several adverse effects associated with synthetic antidiabetic medications. In this study, we investigated the in vitro antidiabetic potential (through inhibition of alpha-glucosidase (AG) and alpha-amylase (AA)) of hydrolysates from lupin proteins pretreated with ultrasound and hydrolyzed using alcalase (ACT) and flavourzyme (FCT). We further fractionated ACT and FCT into three molecular weight fractions. Unfractionated ACT and FCT showed significantly (p < 0.05) higher AG (IC50 value = 1.65 mg/mL and 1.91 mg/mL) and AA (IC50 value = 1.66 mg/mL and 1.98 mg/mL) inhibitory activities than their ultrafiltrated fractions, where lower IC50 values indicate higher inhibitory activities. Then, ACT and FCT were subjected to peptide sequencing using LC-MS-QTOF to identify the potential AG and AA inhibitors. Molecular docking was performed on peptides with the highest number of hotspots and PeptideRanker score to study their interactions with AG and AA enzymes. Among the peptides identified, SPRRF, FE, and RR were predicted to be the most active peptides against AG, while AA inhibitors were predicted to be RPR, PPGIP, and LRP. Overall, hydrolysates prepared from lupin proteins using alcalase and flavourzyme may be useful in formulating functional food for managing diabetics.

Automated summary

The use of natural ingredients for managing diabetes has become increasingly popular due to the adverse effects of synthetic antidiabetic medications. This study investigated the potential of hydrolysates from lupin proteins treated with ultrasound and hydrolyzed using alcalase and flavourzyme to inhibit alpha-glucosidase and alpha-amylase, enzymes involved in diabetes management. Peptide sequencing and molecular docking analysis identified specific peptides with potential antidiabetic activity. These findings suggest that hydrolysates from lupin proteins could be useful in formulating functional food for managing diabetes.