1. Identification of novel angiotensin converting enzyme (ACE) inhibitory peptides from Pacific saury: In vivo antihypertensive effect and transport route.
- Author
-
Wang S, Zhang L, Wang H, Hu Z, Xie X, Chen H, and Tu Z
- Subjects
- Rats, Humans, Animals, Angiotensin-Converting Enzyme Inhibitors chemistry, Peptidyl-Dipeptidase A metabolism, Molecular Docking Simulation, Tandem Mass Spectrometry, Caco-2 Cells, Rats, Inbred SHR, Peptides chemistry, Antihypertensive Agents chemistry, Hypertension drug therapy
- Abstract
Nature food-derived angiotensin converting enzyme inhibitory peptides (ACEIPs) can be potent and safe therapeutics for many medical illnesses, particularly hypertension. In this study, novel ACEIPs were screened and identified from Pacific saury by bio-activity guided approach through ultrafiltration membrane, Sephadex G-25 and RP-HPLC. The antihypertensive effect of ultrafiltration fraction was confirmed with spontaneous hypertensive rats' (SHRs) model. The peptides sequences of which gave the best activity was identified by Q-Orbitrap-MS/MS and selectively synthesized based on the binding energy of molecular docking. Five peptides VVLASLK, LTLK, LEPWR, ELPPK and LPTEK were synthesized, and the peptide LEPWR (IC
50 = 99.5 μM) showed the best ACE inhibitory ability. Furthermore, LEPWR against ACE in a mixed competitive pattern and formed six hydrogen bonds with ACE. Additionally, the apparent permeability coefficient (Papp ) of LEPWR was 3.56 ± 0.14 × 10-6 cm/s and paracellular transport across tight junctions was the main pathway across the Caco-2 monolayer. Therefore, the Pacific saury is a good material to prepare ACEIPs, but antihypertensive mechanism of peptide LEPWR on SHRs needs further investigation., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors of this manuscript have directly participated in the program execution and/or analysis of this study. The content of this manuscript has not been copyrighted or published before. The content of this manuscript is not currently considered for publication elsewhere., (Copyright © 2023. Published by Elsevier B.V.)- Published
- 2024
- Full Text
- View/download PDF