title: Ala-Val-Phe and Val-Phe: ACE inhibitory peptides derived from insect protein with antihypertensive activity in spontaneously hypertensive rats.
abstract: In this study, we evaluated the stability/bioavailability and in vivo antihypertensive activity of the tripeptide, Ala-Val-Phe, that was recently purified from insect protein (Spodoptera littoralis; Lepidoptera) and that showed in vitro angiotensin converting enzyme (ACE) inhibitory activity. This tripeptide is partly hydrolyzed by mucosal peptidases to Val-Phe, a more potent in vitro ACE inhibitor. In organ bath experiments using rat aorta, Val-Phe showed ACE inhibition, while Ala-Val-Phe did not. Single oral administration (5mg/kg body weight) to spontaneously hypertensive rats led to a significant decrease in blood pressure for both peptides. Docking experiments indicated an active character for Val-Phe and an inactive character for Ala-Val-Phe as potential inhibitors of human ACE. From our results, it can be suggested that after oral administration of Ala-Val-Phe, Val-Phe is released by in vivo peptidases and is responsible for in vivo activity of Ala-Val-Phe. To the best of our knowledge this is the first report of in vivo antihypertensive activity of peptides derived from insect protein.
authors.affiliation: Department of Crop Protection, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
authors.forename: Lieselot
authors.initials: L
authors.lastname: Vercruysse
authors.forename: John
authors.initials: J
authors.lastname: Van Camp
authors.forename: Nicole
authors.initials: N
authors.lastname: Morel
authors.forename: Pierre
authors.initials: P
authors.lastname: Rougé
authors.forename: Griet
authors.initials: G
authors.lastname: Herregods
authors.forename: Guy
authors.initials: G
authors.lastname: Smagghe
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019476:Insect Proteins / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D055550:Protein Stability; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D019476:Insect Proteins; D010455:Peptides; D007703:Peptidyl-Dipeptidase A