Comparison of an angiotensin-I-converting enzyme inhibitory peptide from tilapia (Oreochromis niloticus) with captopril: inhibition kinetics, in vivo effect, simulated gastrointestinal digestion and a molecular docking study

J Sci Food Agric. 2020 Jan 15;100(1):315-324. doi: 10.1002/jsfa.10041. Epub 2019 Nov 7.

Abstract

Background: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking.

Results: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50 = 2.577 μmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE.

Conclusion: LSGYGP, with an IC50 value of 2.577 μmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.

Keywords: SHRs; angiotensin-I-converting enzyme; bioactive peptide; captopril; molecular docking.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / chemistry*
  • Angiotensin-Converting Enzyme Inhibitors / metabolism
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / chemistry*
  • Antihypertensive Agents / metabolism
  • Blood Pressure / drug effects
  • Captopril / administration & dosage
  • Captopril / chemistry*
  • Cichlids
  • Digestion
  • Fish Proteins / chemistry
  • Gastrointestinal Tract / metabolism
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Kinetics
  • Male
  • Molecular Docking Simulation
  • Peptides / chemistry*
  • Peptides / metabolism
  • Peptides / pharmacology
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / metabolism
  • Protein Hydrolysates / chemistry
  • Protein Hydrolysates / metabolism
  • Rats
  • Rats, Inbred SHR

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Fish Proteins
  • Peptides
  • Protein Hydrolysates
  • Captopril
  • Peptidyl-Dipeptidase A