Stability and Transport of Spent Hen-Derived ACE-Inhibitory Peptides IWHHT, IWH, and IW in Human Intestinal Caco-2 Cell Monolayers

Hongbing Fan, Qingbiao Xu, Hui Hong, Jianping Wu

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34 Scopus citations


Ile-Trp-His-His-Thr (IWHHT), initially identified as an ACE inhibitory peptide, was shown to have antioxidant and anti-inflammatory activities in cells and blood pressure lowering activity in animals. IWHHT was degraded into IWH and IW during simulated gastrointestinal digestion. The purpose of this study was to investigate the stability, permeability, and transport pathways of IWHHT, IWH, and IW across intestinal epithelium using human intestinal Caco-2 cell monolayers. IWHHT, IWH, and IW were partly degraded by aminopeptidase N or dipeptidyl peptidase IV, but they were transported intact, with apparent permeability coefficients of (22.0 ± 1.42) × 10-8, (37.5 ± 1.11) × 10-8, and (19.6 ± 0.62) × 10-8 cm s-1, respectively. The results firstly evidenced an important role of aminopeptidase N in cleaving small ACE inhibitory peptides during transport. IWH was transported via both peptide transporter 1 (PepT1) and paracellular route, while IW was via PepT1 and IWHHT was via paracellular route only. Transport of IW implied that hydrophobic peptides (even with a small size), consisting of only highly hydrophobic amino acid residues, might not be transported via paracellular diffusion. This study suggested that all three peptides could pass through the intestinal epithelium and that the degraded IWH and IW might also contribute to the antihypertensive activity of IWHHT.

Original languageEnglish
Pages (from-to)11347-11354
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Issue number43
StatePublished - 2018

Bibliographical note

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© 2018 American Chemical Society. All rights reserved.


  • ACE inhibitory peptides
  • Caco-2 cells
  • brush border membrane peptidase
  • spent hen
  • transepithelial transport

ASJC Scopus subject areas

  • General Chemistry
  • General Agricultural and Biological Sciences


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