Structure and Function Study of Food Protein-Derived ACE Inhibitory Peptides

  • Author / Creator
    Gu, Yuchen
  • Hypertension affects one third of the population worldwide. It is a multifactorial, polygenic disorder which involves the interplay among various risk factors. A number of scientific studies have demonstrated that renin-angiotensin system (RAS), oxidative stress and inflammation interact with each other in regulating the hypertensive response and targeted organ injury. Inhibiting angiotensin I-converting enzyme (ACE) is the key target for controlling high blood pressure. Due to the inevitable adverse side effects of antihypertensive drugs, food-derived compounds, especially food protein-derived peptides have emerged as an alternative strategy in the prevention and management of hypertension. The objectives of this thesis were to 1) identify potent ACE inhibitory peptides from various food proteins by in silico digestion and quantitative structure-activity relationship (QSAR) modeling and to 2) explore their additional antioxidative and anti-inflammatory activities in endothelial cells. A systematic evaluation was performed on 15 food commodities as potential sources of ACE inhibitory peptides. In silico digestion of proteins by thermolysin generated 5709 peptides containing 2 to 6 amino acid residues, and their ACE inhibitory activity was predicted using QSAR modeling. Meat proteins from pork, beef and chicken contain the largest number of potent peptides (IC50 < 10 μM), followed by proteins from milk, egg, soybean and canola, whereas proteins from fish (with the exception of salmon) and cereals (oat and barley) contain the least number of potent peptides. This study has demonstrated that proteins from livestock meat, milk, egg, soybean and canola are good sources of ACE inhibitory peptides. Soybean, bovine latoferrin and spent hen were then selected to validate the prediction. Three tripeptides, LSW (IC50=2.7 µM), IVF (IC50=63.3 µM) and LLF (IC50=63.8 µM) with potent ACE inhibitory activity were characterized from soybean hydrolysates, while LRP (IC50=1.2 ± 0.05 µM) and IWHHT (IC50=9.93 ± 0.65 µM) were characterized from bovine lactoferrin and spent hen, respectively. IWHHT was not resistant to simulated gastrointestinal digestion and produced a mixture of IW, IWH, HHT and HT. IW showed a more potent ACE inhibitory activity (IC50=2.0 ± 0.06 µM). LSW, LRP and IWHHT were all predicted to be released from corresponding food proteins in the computational study. LRP significantly inhibited tumor necrosis factor-alpha (TNF-α) induced vascular inflammation by reducing the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) at 50 µM in endothelial cells. LRP, IWHHT, IWH and IW all significantly reduced the level of superoxide when the cells were subject to serum withdrawal to induce oxidative stress. While IWHHT and IWH significantly reduced the expression of VCAM-1 only in TNF-α induced inflammation. This thesis demonstrated the potential of various food proteins as sources of ACE inhibitory peptides. The ACE inhibitory peptides, with additional antioxidative and anti-inflammatory activities identified in the thesis may enhance their antihypertensive effects by interacting with different elements essential in the pathogenesis of hypertension.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Agricultural, Food, and Nutritional Science
  • Specialization
    • Food Science and Technology
  • Supervisor / co-supervisor and their department(s)
    • Wu, Jianping (Agricultural, Food, and Nutritional Science)
  • Examining committee members and their departments
    • Ozimek, Lech (Agricultural, Food, and Nutritional Science)
    • Jacobs, Rene (Agricultural, Food, and Nutritional Science)
    • Stothard, Paul (Agricultural, Food, and Nutritional Science)
    • FitzGerald, Richard J (Life Sciences)