Identification and characterization of two novel dipeptidyl peptidase-IV inhibitory peptides from the simulated gastrointestinal digestion of Tartary buckwheat proteins.

This study analyzed dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides from Tartary buckwheat (Fagopyrum tataricum) protein hydrolysates, known for managing chronic diseases. Simulated gastrointestinal digestion enhanced the inhibitory activity of DPP-IV. Using anion-exchange resin DEAE-52, reverse high-performance liquid chromatography, and LC-MS/MS, eight novel peptides were identified. Among them, the peptides LAGQS (LA5) and LREIDDADK (LR9) exhibited the strongest inhibition in both competitive and noncompetitive modes. Molecular docking revealed electrostatic, hydrogen bond, and hydrophobic interactions for both peptides, with LR9 also engaging in π-cation interactions. Based on the Caco-2 model, the in situ DPP-IV inhibitory effect of LR9 was superior to that of LA5, likely because of LR9's greater stability during hydrolysis. Moreover, LA5 could not be transported through the Caco-2 monolayer, and LR9 demonstrated moderate transportability. These findings highlight Tartary buckwheat protein's potential for application in high-value plant-based products, including functional foods and pharmaceuticals targeting blood glucose regulation using DPP-IV inhibitory peptides.