Food Chem. 2026 Nov 2;533(Pt 1):151808. doi: 10.1016/j.foodchem.2026.151808. Online ahead of print.
ABSTRACT
The escalating prevalence of type 2 diabetes mellitus necessitates the development of safe and effective α-glucosidase inhibitors from natural food sources. This study employed an integrated strategy combining peptidomics, computational screening, and molecular dynamics (MD) simulation to discover novel α-glucosidase inhibitory peptides from hemp seed protein hydrolysates. Nano-LC-MS/MS identified 4875 unique peptides, predominantly short-chain sequences (<1000 Da), from which 16 high-confidence candidates were selected through multi-parameter in silico filtering. Molecular docking prioritized seven peptides, with experimental validation confirming four potent inhibitors (YQF, YLY, FRF, and FGPE) exhibiting IC₅₀ values of 4.45-6.49 mg/mL. Kinetic analysis revealed mechanistic diversity: FRF displayed competitive inhibition, whereas YQF, YLY, and FGPE exhibited non-competitive inhibition. 200-ns MD simulations demonstrated stable peptide-enzyme complexes, with hydrogen bonding to catalytic residues and hydrophobic interactions driving sustained inhibition. These hemp-derived peptides represent candidate functional ingredients for potential glycemic management applications. While in vivo validation remains to be performed, the integrated workflow establishes a foundation for mechanism-based screening of antidiabetic food peptides.
PMID:42981942 | DOI:10.1016/j.foodchem.2026.151808