Seabuckthorn Seed Meal Protein-Based Inhibitory Peptides Targeting Multiple Hyperglycemic Enzymes: Optimization of Process and Probing of Mechanisms

This work utilized seabuckthorn seed meal protein (SSP) to develop hypoglycemic peptides via controlled protease catalyzed hydrolysis. Among the SSP hydrolysates (SSPHs) obtained by means of various proteases, the SSP hydrolyzed by dispase (SSPD) exhibited extraordinary inhibitory abilities against three key enzymes involved in glucose metabolism: α-glucosidase, α-amylase, and dipeptidyl peptidase-IV (DPP-IV). Following process optimization and purification, SSPD displayed remarkable inhibitions to <i>α</i>-glucosidase (IC₅₀: 3.45 ± 0.18 mg/mL) and DPP-IV (IC₅₀: 5.01 ± 0.21 mg/mL), respectively. Molecular docking analysis and in vitro verification revealed three peptides in the SSPD with <i>α</i>-glucosidase inhibition: FHF, FFI, and FGI (IC₅₀: 3.98 ± 0.16 mM, 8.21 ± 0.21 mM, 11.57 ± 0.20 mM), and three peptides with DPP-IV inhibition: IYF, IGF, and LFF (IC₅₀: 5.32 ± 0.15 mM, 7.17 ± 0.14 mM, 7.62 ± 0.19 mM). These findings demonstrate that SSP holds promise as a significant natural resource for the creation of multifunctional hypoglycemic peptides, which can be utilized in nutritional and functional food applications.