Characterization and efficacy of α-glucosidase inhibitory peptides from enzymatically hydrolyzed Peanut meal

Natural substances with α-glucosidase inhibitory activity have emerged as promising agents for the effective treatment of diabetes. In this study, peanut meal (PM) was enzymatically hydrolyzed using three proteases and fractionated by ultrafiltration. Among the resulting fractions, peanut peptide (PEP) in the 3 kDa-500 Da range demonstrated superior α-glucosidase inhibitory activity (69.5 %), peptide yield (85.75 %), and peptide content (1.55 ± 0.05 mg/mL). In a high-fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetes (T2DM) mouse model, high-dose PEP (PEP-H) effectively reduced blood glucose and lipid levels, alleviated liver damage, and relieved the symptoms of T2DM. Immunohistochemical and western blot analyses revealed that PEP modulated hepatic glucose and lipid metabolism via the PI3K/Akt/GSK-3β signaling pathway. Finally, four peptides (AFPKFR, APPFDPNKPK, PFPIK, and FATPVPLPK) exhibiting the strongest α-glucosidase-binding ability were identified from PEP using LC-MS/MS and molecular docking analysis. Notably, APPFDPNKPK and FATPVPLPK exhibited the highest inhibitory activity (64.3 % and 75.4 %, respectively) via mixed-type inhibition. This study highlights a novel value-added strategy for the utilization of PM proteins and provides essential peptide candidates for developing innovative antidiabetic drugs and functional foods.