Abstract:The activity of inhibitory peptide (IPQVS) of dipeptidyl peptidase-4 (DPP-IV) was studied based on the Caco-2 cell model, and the effects of intestinal absorption and degradation on the inhibitory activity of DPP-IV were evaluated. The apparent absorption rate(Papp) values of IPQVS and their degraded peptide fragments were measured as (1.35±0.09)×10-6 cm/s, (1.46±0.18)×10-6 cm/s, (0.95±0.08)×10-6 cm/s and (3.01±0.15)×10-6 cm/s, respectively. IPQVS was mainly transported across Caco-2 cell monolayers through endocytosis. IPQVS inhibited the DPP-IV activity in the Caco-2 cell monolayer in a dose-dependent manner, and mRNA expression in DPP-IV was not affected (P>0.05). The IC50 value was (101.66±6.02) μmol/L, which was higher than that measured in vitro by chemical substrate method. The results of molecular docking showed that the binding of DPP-IV with the degradation products of IPQVS, i.e., PQVS and QVS, was weaker than binding with IPQVS, and the binding sites were also significantly reduced, which greatly restricted the DPP-IV inhibitory activity of IPQVS.
