Spent hen muscle protein-derived ras regulating peptides shows antioxidant activity in vascular cells

Hongbing Fan, Khushwant S. Bhullar, Jianping Wu

Research output: Contribution to journalArticlepeer-review

21 Citations (SciVal)


Spent hens are egg-laying hens reaching the end of their egg-laying cycles, being a major byproduct of the egg industry. Recent studies have been focusing on finding new value-added uses for spent hens. We have previously identified four bioactive peptides from spent hen muscle proteins, including three angiotensin-converting enzyme (ACE) inhibitory (ACEi) peptides (VRP, LKY, and VRY), and one ACE2 upregulating (ACE2u) peptide (VVHPKESF (V-F)). In the current study, we further assessed their antioxidant and cytoprotective activities in two vascular cell lines—vascular smooth muscle A7r5 cells (VSMCs) and endothelial EA.hy926 cells (ECs)—upon stimulation by tumor necrosis factor alpha (TNFα) and angiotensin (Ang) II, respectively. The results from our study revealed that all four peptides attenuated oxidative stress in both cells. None of the investigated peptides altered the expression of TNFα receptors in ECs; however, VRY and V-F downregulated Ang II type 1 receptor (AT1R), while V-F upregulated the Mas receptor (MasR) in VSMCs. Further, we found that the antioxidant effects of VRP, LKY, and VRY were likely through acting as direct radical scavengers, while that of V-F was at least partially ascribed to increased endogenous antioxidant enzymes (GPx4 and SOD2) in both cells. Besides, as an ACE2u peptide, V-F exerted antioxidant effect in a MasR-dependent manner, indicating a possible involvement of the upregulated ACE2-MasR axis underlying its antioxidant action. The antioxidant activities of VRP, LKY, VRY, and V-F in vascular cells indicated their multifunctional properties, in addition to their ACEi or ACE2u activity, which supports their potential use as functional food ingredients against hypertension.

Original languageEnglish
Article number290
Pages (from-to)1-14
Number of pages14
Issue number2
StatePublished - Feb 2021

Bibliographical note

Funding Information:
This research was funded by Natural Sciences and Engineering Research Council of Canada, Egg Farmers of Canada, and Burnbrae Farms Ltd.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • ACE
  • ACE2
  • Antioxidant enzymes
  • Antioxidant peptides
  • Chicken
  • Laying hen
  • Muscle protein
  • Oxidative stress

ASJC Scopus subject areas

  • Food Science
  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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