Mechanism Analysis of a Novel Angiotensin-I-Converting Enzyme Inhibitory Peptide from Isochrysis zhanjiangensis Microalgae for Suppressing Vascular Injury in Human Umbilical Vein Endothelial Cells

J Agric Food Chem. 2020 Apr 15;68(15):4411-4423. doi: 10.1021/acs.jafc.0c00925. Epub 2020 Apr 2.

Abstract

Microalgae are primary producers with multiple nutrients in aquatic environments and mostly have applications in biological feed and fuel industry. There are few studies assessing the angiotensin-I-converting enzyme (ACE) inhibition potential of Isochrysis zhanjiangensis, other than its antioxidant potential. In this study, we evaluated a peptide from I. zhanjiangensis (PIZ, FEIHCC) and its vascular endothelial factors and mechanism in human umbilical vein endothelial cells (HUVEC). The results reveal that PIZ (IC50 = 61.38 μM) acts against ACE in a non-competitive binding mode. In addition, PIZ inhibits angiotensin II (Ang II)-induced vascular factor secretion and expression by blocking inflammation and apoptosis through nuclear factor κB (NF-κB), nuclear erythroid 2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), and the serine/threonine kinase (Akt) signal pathways. This study reveals that PIZ has potential to be developed as a therapeutic agent for hypertension and provides a new method of high-value utilization of I. zhanjiangensis.

Keywords: HUVEC; Isochrysis zhanjiangensis; angiotensin-I-converting enzyme; in silico; peptide.

MeSH terms

  • Angiotensin II / genetics
  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / chemistry
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Apoptosis / drug effects
  • Haptophyta / chemistry*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Microalgae / chemistry*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Vascular System Injuries / drug therapy
  • Vascular System Injuries / genetics
  • Vascular System Injuries / metabolism*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • Peptides
  • Plant Extracts
  • Angiotensin II
  • Peptidyl-Dipeptidase A