Two novel peptides derived from oat with inhibitory activity against dipeptidyl peptidase-IV: the related mechanism revealed by molecular docking and in vitro and in situ effects

In recent years, the dipeptidyl peptidase IV (DPP-IV) inhibitors, an antidiabetic drug extending the half-life of incretin, have attracted the researchers’ attention. The current study aimed to explore the inhibitory peptides obtained from oat protein hydrolysates (OPHs) and their derivative peptides against DPP-IV. OPHs obtained by digestion with alcalase, papain, and trypsin exhibited DPP-IV inhibitory activities. Among them, the OPHs produced by digestion with alcalase exhibited the strongest inhibitory effects on DPP-IV (92.92 ± 0.13%). The inhibitory peptides obtained with alcalase digestion were isolated and purified using anion-exchange chromatography (DEAE-52) and volume-exclusion chromatography (Sephadex-G25) sequentially. Liquid chromatography-tandem mass spectrometry was used to identify 11 peptides in total. Molecular docking results showed that the SPVAEVPFLR (SP10, − 8.0 kcal/mol) and LDATDMVALVG (LD11, − 7.1 kcal/mol) had the lowest binding energies with DPP-IV and primarily bound by hydrogen bonds and hydrophobic interactions. Moreover, simulated digestion verified that SP10 and LD11 could resist gastrointestinal degradation. The inhibitory activities of SP10 and LD11 on DPP-IV were investigated in vitro using a monolayer intestinal model of Caco-2 cells. The results indicated that SP10 and LD11 had in situ IC₅₀ values of 167.8 and 269.1 µM, respectively. Therefore, OPHs can be considered promising natural sources of DPP-IV inhibitory peptides.