Dipeptidyl Peptidase-IV Inhibitory Activity of Katsuobushi-Derived Peptides in Caco-2 Cell Assay and Oral Glucose Tolerance Test in ICR Mice

J Agric Food Chem. 2020 Jun 10;68(23):6355-6367. doi: 10.1021/acs.jafc.0c01942. Epub 2020 May 27.

Abstract

Proteolytic products of bonito stock residue inhibit dipeptidyl peptidase-IV (DPP-IV). Here, we isolated, purified, and identified the components of its N5 fraction obtained after using neutral protease from Aspergillus oryzae. A 10% ethanol eluent (N5-2 fraction) from column chromatography was sequenced, yielding 18 peptides. Of these, Glu-Val-Phe, Ala-Val-Phe, and Gly-Val-Phe were identified as novel (IC50 values for DPP-IV inhibition were 525.56, 5466.49, and 2870.87 μM, respectively), whereas Trp-Val is the primary peptide (IC50 value of 36.99 μM, 1359 unit (mL/100 g N5-2 fraction) = (yield (mg)/100 g N5-2 fraction)/IC50 (μg/mL). Furthermore, the N5-2 fraction significantly decreased DPP-IV activity in Caco-2 intestinal epithelial cells (p < 0.05). From the oral glucose tolerance test using ICR mice, the N5-2 fraction significantly attenuated the rise in serum glucose levels compared with the control (p < 0.05) through cell-surface DPP-IV inhibition. We discuss the novelty, significance, and relevance of the findings in this study, as well as its broad applications for prevention of diabetes.

Keywords: Caco-2 cell peptide addition test; DPP-IV inhibition peptide; Katsuobushi peptide; dipeptidyl peptidase IV activity inhibition; peptide oral administration OGTT test; postprandial hyperglycemia; suppression of glucose increase.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Peptides / administration & dosage*
  • Peptides / chemistry

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Peptides
  • Dipeptidyl Peptidase 4
  • Glucose