LAUSR

BACKGROUND Type 2 diabetes mellitus (T2DM) is a serious threat to human health. Owing to the action of DPP-IV, the half-life of entero-insulin hormone after secretion is extremely short, causing insufficient insulin secretion in diabetic patients. Dipeptidyl peptidase-IV (DPP-IV) inhibitors can be used as a new treatment for T2DM. In this study, the proteins of eel (Anguilla rostrata) scraps hydrolyzed using Protamex® protease (EPHs) were found to have forceful DPP-IV inhibitory activity, and it also provided research ideas for the development and utilization of eel (Anguilla rostrata) scraps. RESULTS The IC50 value of EPHs was 5.455 ± 0.24 mg·mL-1 . The peptide fractions with the highest DPP-IV inhibitory activity were sequentially separated by ultrafiltration, gel filtration chromatography (GFC), and reversed-phase high performance liquid chromatography (RP-HPLC) in a continuous hierarchical manner and analyzed using matrix-assisted laser desorption/ionization time-of-flight/ time-of-flight mass spectrometry/ mass spectrometry (MALDI-TOF/TOF MS/MS). Three peptides revealed significant inhibitory activity were screened among the identified sequences, with sequences of Phe-Pro-Arg (IC50 = 62.14 ± 1.47 μM), Tyr-Pro-Pro-Ser-Phe-Ser (IC50 = 102.65 ± 4.57 μM), and Tyr-Pro-Tyr-Pro-Ala-Ser (IC50 = 68.30 ± 3.85 μM). Molecular docking simulations revealed that their inhibitory effect was mainly due to the formation of hydrogen bonds with amino acid residues in the active sites of DPP-IV. Analysis of the inhibition patterns of the synthetic peptides displayed that Phe-Pro-Arg and Tyr-Pro-Pro-Ser-Phe-Ser displayed competitive inhibition, while Tyr-Pro-Tyr-Pro-Ala-Ser showed mixed competitive/non-competitive inhibition. CONCLUSIONS The protein hydrolysates isolated from eel scraps are potential functional food ingredients for the treatment of T2DM. This article is protected by copyright. All rights reserved.