Identification of a hepatoprotective peptide in wheat gluten hydrolysate against D-galactosamine-induced acute hepatitis in rats

J Agric Food Chem. 2013 Jul 3;61(26):6304-10. doi: 10.1021/jf400914e. Epub 2013 Jun 19.

Abstract

A hepatoprotective peptide, pyroglutamyl leucine (pyroGlu-Leu), was identified in wheat gluten hydrolysate through an in vivo activity-guided fractionation approach based on D-galactosamine-induced acute hepatitis in rats and fractionation of peptides with large-scale preparative ampholine-free isoelectric focusing. The active acidic fraction predominantly consisted of pyroglutamyl peptides and free pyroglutamic acid. Pyroglutamyl peptides were derivatized with phenyl isothiocyanate after removal of a pyroglutamyl residue by pyroglutamate aminopeptidase. The derivatives were purified by reversed-phase HPLC and subjected to sequence analysis. The active fraction contained pyroGlu-Ile, pyroGlu-Leu, pyroGlu-Gln, pyroGlu-Gln-Gln, and free pyroGlu. Ingestion of pyroGlu-Leu at 20 mg/kg body weight significantly decreased serum aspartate and alanine aminotransferases to approximately 30% and 20% of those values of the vehicle group, respectively, which were near the normal levels. Thirty minutes after ingestion of pyroGlu-Leu at 20 mg/kg, the concentration of pyroGlu-Leu in portal blood plasma increased to approximately 2 μM.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Dipeptides / chemistry
  • Dipeptides / isolation & purification
  • Dipeptides / metabolism
  • Dipeptides / therapeutic use*
  • Disease Models, Animal*
  • Galactosamine
  • Glutens / metabolism*
  • Hepatitis / blood
  • Hepatitis / prevention & control*
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Peptide Fragments / metabolism
  • Peptide Fragments / therapeutic use
  • Protective Agents / chemistry
  • Protective Agents / isolation & purification
  • Protective Agents / metabolism
  • Protective Agents / therapeutic use*
  • Protein Hydrolysates / chemistry
  • Pyrrolidonecarboxylic Acid / analogs & derivatives*
  • Pyrrolidonecarboxylic Acid / chemistry
  • Pyrrolidonecarboxylic Acid / isolation & purification
  • Pyrrolidonecarboxylic Acid / metabolism
  • Pyrrolidonecarboxylic Acid / therapeutic use
  • Rats
  • Triticum / chemistry*

Substances

  • Biomarkers
  • Dipeptides
  • Peptide Fragments
  • Protective Agents
  • Protein Hydrolysates
  • pyroglutamylleucine
  • Galactosamine
  • Glutens
  • Pyrrolidonecarboxylic Acid