Antihypertensive Effects in Vitro and in Vivo of Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Bovine Bone Gelatin Hydrolysate

J Agric Food Chem. 2020 Jan 22;68(3):759-768. doi: 10.1021/acs.jafc.9b05618. Epub 2019 Dec 31.


In this study, we investigated the antihypertensive effects in vitro and in vivo of novel angiotensin-converting enzyme inhibitory (ACEI) peptides purified and identified from bovine bone gelatin hydrolysate (BGH). Thirteen ACEI peptides were identified from BGH, and among which, RGL-(Hyp)-GL and RGM-(Hyp)-GF exhibited high ACE inhibition with IC50 values of 1.44 and 10.23 μM. Molecular docking predicted that RGM-(Hyp)-GF and ACE residues of Glu384, His513, and Lys511 formed hydrogen-bonding interactions at distances of 2.57, 2.99, and 2.42 + 3.0 Å. RGL-(Hyp)-GL formed hydrogen bonds with Lys511 and Tyr523 and generated hydrogen-bonding interactions with His387 and Glu411 in the zinc(II) complexation motif at distances of 2.74 and 3.03 + 1.93 Å. The maximal decrements in systolic blood pressure in spontaneously hypertensive rats induced by one-time gavage of RGL-(Hyp)-GL and RGM-(Hyp)-GF at 30 mg/kg were 31.3 and 38.6 mmHg. RGL-(Hyp)-GL had higher enzyme degradation resistance than that of RGM-(Hyp)-GF in vitro incubation in rat plasma, and they were sequentially degraded into pentapeptides and tetrapeptides within 2 h. Our results indicate that BGH can serve as a nutritional candidate to control blood pressure.

Keywords: ACE; SHRs; bovine bone gelatin; molecular docking; peptide.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / chemistry*
  • Angiotensin-Converting Enzyme Inhibitors / isolation & purification
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / chemistry*
  • Antihypertensive Agents / isolation & purification
  • Blood Pressure / drug effects
  • Bone and Bones / chemistry*
  • Cattle
  • Gelatin / chemistry*
  • Humans
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Male
  • Molecular Docking Simulation
  • Peptides / administration & dosage
  • Peptides / chemistry*
  • Peptides / isolation & purification
  • Peptidyl-Dipeptidase A / chemistry
  • Protein Hydrolysates / chemistry
  • Rats
  • Rats, Inbred SHR


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Peptides
  • Protein Hydrolysates
  • Gelatin
  • Peptidyl-Dipeptidase A