PMID- 36661748 OWN - NLM STAT- MEDLINE DCOM- 20230406 LR - 20230406 IS - 1097-0010 (Electronic) IS - 0022-5142 (Linking) VI - 103 IP - 7 DP - 2023 May TI - Purification and characterization of the dipeptidyl peptidase-IV inhibitory peptides from eel (Anguilla rostrata) scraps enzymatic hydrolysate for the treatment of type 2 diabetes mellitus. PG - 3714-3724 LID - 10.1002/jsfa.12462 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a serious threat to human health. Owing to the action of dipeptidyl peptidase-IV (DPP-IV), the half-life of entero-insulin hormone after secretion is extremely short, causing insufficient insulin secretion in diabetic patients. Dipeptidyl peptidase-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 strong DPP-IV inhibitory activity. The study also provided research ideas for the development and utilization of A. rostrata scraps. RESULTS: The median inhibition concentration (IC(50) ) 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 that revealed significant inhibitory activity were screened among the identified sequences, with sequences of Phe-Pro-Arg (IC(50) = 62.14 +/- 1.47 muM), Tyr-Pro-Pro-Ser-Phe-Ser (IC(50) = 102.65 +/- 4.57 muM), and Tyr-Pro-Tyr-Pro-Ala-Ser (IC(50) = 68.30 +/- 3.85 muM). 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, whereas 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. (c) 2023 Society of Chemical Industry. CI - (c) 2023 Society of Chemical Industry. FAU - Cao, Hongzhen AU - Cao H AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. FAU - Di, Nana AU - Di N AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. FAU - Jiang, Bo AU - Jiang B AUID- ORCID: 0000-0002-0638-6456 AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, China. FAU - Chen, Jingjing AU - Chen J AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, China. FAU - Zhang, Tao AU - Zhang T AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, China. LA - eng GR - Guangxi Zhongnan Fisheries Co., Ltd/ GR - Chongzuo Scientific Research Project/ PT - Journal Article DEP - 20230205 PL - England TA - J Sci Food Agric JT - Journal of the science of food and agriculture JID - 0376334 RN - 0 (Peptides) RN - EC 3.4.14.5 (Dipeptidyl Peptidase 4) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Animals MH - Humans MH - *Anguilla/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/veterinary MH - Tandem Mass Spectrometry MH - Molecular Docking Simulation MH - Peptides/chemistry MH - Dipeptidyl Peptidase 4/chemistry MH - *Dipeptidyl-Peptidase IV Inhibitors/chemistry OTO - NOTNLM OT - DPP-IV inhibitory peptides OT - T2DM OT - eel (Anguilla rostrata) scraps OT - hydrolysis OT - purification EDAT- 2023/01/21 06:00 MHDA- 2023/04/06 06:42 CRDT- 2023/01/20 09:35 PHST- 2023/01/06 00:00 [revised] PHST- 2022/09/01 00:00 [received] PHST- 2023/01/20 00:00 [accepted] PHST- 2023/04/06 06:42 [medline] PHST- 2023/01/21 06:00 [pubmed] PHST- 2023/01/20 09:35 [entrez] AID - 10.1002/jsfa.12462 [doi] PST - ppublish SO - J Sci Food Agric. 2023 May;103(7):3714-3724. doi: 10.1002/jsfa.12462. Epub 2023 Feb 5.