egg-white and Hypertension

The avian egg is an important source of nutrients, containing all of the proteins, lipids, vitamins, minerals, and growth factors required by the developing embryo, as well as a number of defense factors to protect against bacterial and viral infection. Moreover, eggs are now understood to contain substances with biological functions beyond basic nutrition, and extensive research has been undertaken to identify and characterize these biologically active components. This review mainly focused on biological activities of proteins and peptides derived from egg components. Several biological activities have now been associated with egg components, including novel antimicrobial activities, antiadhesive properties, immunomodulatory, anticancer, and antihypertensive activities, antioxidant properties, protease inhibitors, nutrient bioavailability, and functional lipids, highlighting the importance of egg and egg components in human health and in disease prevention and treatment. Continued research to identify new and existing biological functions of hen egg components will help to define new methods to further improve the value of eggs as a source of numerous biologically active compounds with specific benefits for human and animal health and secure their role in the therapy and prevention of chronic and infectious disease.

Topics: Animals; Anti-Infective Agents; Antioxidants; Egg Proteins; Egg White; Egg Yolk; Eggs; Health Promotion; Humans; Hypertension; Immunity; Neoplasms; Nutritional Physiological Phenomena

The kidney is an important target organ in the treatment of hypertension, but the effect of peptide QIGLF with antihypertensive activity on kidneys remains unknown. In the work, we aimed to further understand the hypotensive effects of QIGLF in spontaneously hypertensive rats (SHRs) using widely targeted metabolomics technology to investigate the kidney metabolic profiling variations. After four weeks of oral administration, the results showed different renal metabolomics profiles between QIGLF and model groups. Besides, a total of 10 potential biomarkers were identified, that is, 3-hydroxybutanoate, 20-hydroxyeicosatetraenoic acid, 19(S)-hydroxyeicosatetraenoic acid, 15-oxoETE, L-ornithine, malonate, uridine, uridine 5'-monophosphate, argininosuccinic acid, and N-carbamoyl-L-aspartate. These metabolites might exhibit antihypertensive activity of QIGLF by regulating synthesis and degradation of ketone bodies, arachidonic acid metabolism, pyrimidine metabolism, and arginine biosynthesis. These findings suggest that QIGLF might alleviate hypertension by inhibiting renal inflammation, promoting natriuresis, and regulating renal nitric oxide production.

Topics: Animals; Antihypertensive Agents; Egg White; Hypertension; Kidney; Metabolomics; Peptides; Rats

Previous work has shown that egg white-derived peptide QIGLF has significant in vivo antihypertensive activity. This study aimed to clarify the antihypertensive mechanisms of QIGLF on spontaneously hypertensive rats (SHRs) by a serum proteomic approach. Here, the tandem mass tag (TMT) quantitative proteomic was performed to discover serum protein changes in SHRs with QIGLF. As a result, SHRs with 4 weeks of QIGLF treatment have distinct serum protein expression profiles by principal component and Pearson's correlation coefficient analysis. Based on Gene Ontology (GO) annotation, oxygen transport and organelle fusion were found to be a regulated major biological process. Besides, aldosterone regulated sodium reabsorption, mitophagy, gap junction, and tight junction were significantly regulated based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. QIGLF might exert antihypertensive effects in the SHRs by inhibiting Na

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Egg White; Hypertension; Peptides; Proteomics; Rats; Rats, Inbred SHR

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Egg White; Hypertension; Metabolomics; Peptides; Rats; Rats, Inbred SHR

The vasoconstricting effect of angiotensin II (Ang II) is mediated by Ang II type I receptor (AT1R); blocking or blunting AT1R is a key strategy for the development of antihypertensive drugs. Our previous study showed that the blood pressure lowering the activity of egg white hydrolysate (EWH) in spontaneously hypertensive rats was due to the downregulation of aortic AT1R expression, which promoted us to further identify the AT1R downregulating peptides in the present study. The protein expression of AT1R in a rat aortic vascular smooth muscle cell line A7r5 cells was used for the activity test. The hydrolysate was fractionated stepwise by C18 Sep-Pack cartridge and reverse-phase chromatography, and the peptide sequences were characterized by LC-MS/MS. Peptides including ITKPNDVYS, VVGSAEAGVDAAS, AVHAAHAEINEAGRE, AGREVVGSAEAGVD, and VVGSAEAGVD, were identified. ITKPNDVYS showed the most potent peptide for lowering the level of AT1R in A7r5 cells. These results suggested that ITKPNDVYS is the responsible peptide for lowering the AT1R level in EWH. PRACTICAL APPLICATIONS: A new peptide ITKPNDVYS was identified as a downregulator of AT1R from egg white hydrolysate, which provides a new approach for the development of food protein-derived antihypertensive peptides as nutraceuticals or functional food ingredients.

Topics: Angiotensin II; Animals; Chromatography, Liquid; Egg White; Hypertension; Peptides; Rats; Receptor, Angiotensin, Type 1; Tandem Mass Spectrometry

Egg proteins are recognized as excellent sources of bioactive peptides, such as angiotensin-converting enzyme inhibitory (ACEi) peptides. Oral administration of a thermolysin-digested egg white hydrolysate (T-EWH) caused a significant blood pressure reduction in spontaneously hypertensive rats; a further ACEi assay implied that its ACEi activity was enhanced after in vitro gastrointestinal (GI) digestion. These results indicated that T-EWH contained ACEi peptides resisting GI digestion and/or being further released during GI digestion. Therefore, the objective of this study was to identify these responsible ACEi peptides from T-EWH. The conventionally activity-guided fractionation was applied, coupled with a synchronized GI digestion throughout, during which both peptide yield and ACEi activity before and after the GI digestion were measured. Finally, six ACEi peptides (LAPYK, LKISQ, LKYAT, INKVVR, LFLIKH, and LGHWVY) with good GI resistance were identified with IC

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Chickens; Digestion; Egg Proteins; Egg White; Gastrointestinal Tract; Hypertension; Peptides; Peptidyl-Dipeptidase A; Protein Hydrolysates; Rats; Rats, Inbred SHR

Excessive proliferation, inflammation, oxidative stress, and migration induced by angiotensin II (Ang II), occurring in vascular smooth muscle cells (VSMCs) during vascular remodelling, are major pathogenesis of hypertension. Antihypertensive peptides derived from food proteins are promising alternatives in preventing/treating hypertension and associated complications. In addition to reducing high blood pressure in spontaneously hypertensive rats, egg white ovotransferrin-derived antihypertensive IRW (Ile-Arg-Trp) was shown to exert antiproliferative, antioxidant, and anti-inflammatory effects in A7r5 cells (a vascular smooth muscle cell line) against Ang II stimulation, further indicating its potential in retarding vascular remodelling. Since its regulatory role in migration of VSMC is unclear, the objective of this study was to evaluate the antimigrant activity of IRW in Ang II-stimulated A7r5 cells. It was found that IRW could downregulate matrix metallopeptidase 9 (MMP9) expression and inhibit migration of Ang II-stimulated A7r5 cells, which was associated with inactivation of p38/MAPK signaling. More importantly, the antimigrant activity of IRW in Ang II-stimulated A7r5 cells was dependent on angiotensin type I receptor (AT1R). Our study provided the first evidence that egg ovotransferrin-derived antihypertensive peptide IRW inhibited migration of VSMCs.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Cell Movement; Egg White; Humans; Hypertension; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Peptides; Rats; Receptor, Angiotensin, Type 1; Signal Transduction

In this study, a novel angiotensin-converting enzyme (ACE)-inhibitory tripeptide (IVR) was isolated and identified from unfertilized soft-shelled turtle egg white (SSTEW). The IC50 value of IVR was measured in vitro as low as 0.81 ± 0.03 μM, and its inhibition type was suggested as competitive according to the Lineweaver-Burk plot. This peptide can be generated from either thermolysin followed by trypsin digestion (two stages) or only trypsin digestion (one stage). Quantitative LC-MS/MS analysis indicated that two-stage digestion gave 3.14 ± 0.17 mg of IVR from 1 g of SSTEW, better than that from one-stage digestion (1.31 ± 0.12 mg). In vivo antihypertensive activity of the tripeptide IVR after single oral administration (0.1 and 1 mg/kg of body weight) led to a significant reduction in systolic blood pressure 2-4 h after administration in spontaneously hypertensive rats. In addition, the binding mechanism of IVR has been rationalized through docking simulations using the testicular ACE (tACE)-lisinopril complex at 2 Å resolution (PDB 108A ). The best docking pose was located at the tACE catalytic site resembling the mode of inhibition exerted by lisinopril, an effective hypertensive synthetic drug. The degree of inhibition of this peptide correlated with the H-bond interaction between the C-terminal of IVR and Lys511 and Tyr520 residues of tACE, a significant inhibitor registration for lisinopril. This study illustrated that IVR behaves as a transition-state analogue inhibitor and is useful in therapeutic intervention for blood pressure control. To the best of our knowledge, this is the first report of an efficient ACE-inhibitory tripeptide generated from the unfertilized egg of soft-shelled turtle.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Biocatalysis; Blood Pressure; Egg White; Humans; Hypertension; Kinetics; Male; Molecular Docking Simulation; Peptides; Peptidyl-Dipeptidase A; Rats; Rats, Inbred SHR; Trypsin; Turtles

We have previously characterized several antihypertensive peptides in simulated digests of cooked eggs and showed blood pressure lowering property of fried whole egg digest. However, the long-term effects of this hydrolysate and its fractions on blood pressure are not known. Therefore, the objectives of the study were to determine the effects of long term administration of fried whole egg hydrolysate and its fractions (i.e. egg white and egg yolk) on regulation of blood pressure and associated factors in cardiovascular disease such as plasma lipid profile and tissue oxidative stress.. We used spontaneously hypertensive rats (SHR), an animal model of essential hypertension. Hydrolysates of fried egg and its fractions were prepared by simulated gastro-intestinal digestion with pepsin and pancreatin. 16-17 week old male SHRs were orally administered fried whole egg hydrolysate, non-hydrolyzed fried whole egg, egg white hydrolysate or egg yolk hydrolysates (either defatted, or not) daily for 18 days. Blood pressure (BP) and heart rate were monitored by telemetry. Animals were sacrificed at the end of the treatment for vascular function studies and evaluating plasma lipid profile and tissue oxidative stress. BP was reduced by feeding fried whole egg hydrolysate but not by the non-hydrolyzed product suggesting a critical role for in vitro digestion in releasing anti-hypertensive peptides. Egg white hydrolysate and defatted egg yolk hydrolysate (but not egg yolk hydrolysate) also had similar effects. Reduction in BP was accompanied by the restoration of nitric oxide (NO) dependent vasorelaxation and reduction of plasma angiotensin II. Fried whole egg hydrolysate also reduced plasma levels of triglyceride although it was increased by the non-hydrolyzed sample. Additionally the hydrolyzed preparations attenuated tissue oxidative stress.. Our results demonstrate that fried egg hydrolysates exert anti-hypertensive effects, improve plasma lipid profile and attenuate tissue oxidative stress in vivo.

Topics: Angiotensin II; Animals; Blood Pressure; Egg White; Essential Hypertension; Humans; Hypertension; Nitric Oxide; Oxidative Stress; Protein Hydrolysates; Rats; Rats, Inbred SHR

There is a growing interest in using functional food components as therapy for cardiovascular diseases such as hypertension. We have previously characterized a tri-peptide IRW (Ile-Arg-Trp) from egg white protein ovotransferrin; this peptide showed anti-inflammatory, anti-oxidant and angiotensin converting enzyme (ACE) inhibitor properties in vitro. Given the pathogenic roles played by angiotensin, oxidative stress and inflammation in the spontaneously hypertensive rat (SHR), we tested the therapeutic potential of IRW in this well-established model of hypertension.. 16-17 week old male SHRs were orally administered IRW at either a low dose (3 mg/Kg BW) or a high dose (15 mg/Kg BW) daily for 18 days. Blood pressure (BP) and heart rate were measured by telemetry. Animals were sacrificed at the end of the treatment for vascular function studies and measuring markers of inflammation. IRW treatment attenuated mean BP by ~10 mmHg and ~40 mmHg at the low- and high-dose groups respectively compared to untreated SHRs. Heart rate was not affected. Reduction in BP was accompanied by the restoration of diurnal variations in BP, preservation of nitric oxide dependent vasorelaxation, as well as reduction of plasma angiotensin II, other inflammatory markers and tissue fibrosis.. Our results demonstrate anti-hypertensive effects of IRW in vivo likely mediated through ACE inhibition, endothelial nitric oxide synthase and anti-inflammatory properties.

Topics: Animals; Antihypertensive Agents; Blood Vessels; Blotting, Western; Circadian Rhythm; Egg White; Fluorescent Antibody Technique; Hypertension; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Nitrosation; Oligopeptides; Oxidative Stress; Rats; Rats, Inbred SHR; Telemetry

This paper evaluates the effects of the short- (1 g/kg) and long-term (0.5 and 1 g/kg/day) oral intake of egg white hydrolysed with pepsin (hEW) and the long-term oral intake (1 g/kg/day) of egg white (EW) on local angiotensin-converting enzyme (ACE) activities in plasma and other tissues of spontaneously hypertensive rats (SHR), as compared to the effect of the ACE inhibitor prototype captopril. The rats treated with hEW were classed in a different group than the control rats and the rats treated with EW by cluster analysis, taking into account their tissue ACE activities and their systolic blood pressure (SBP). Principal component analysis (PCA) showed that SBP in SHR was negatively related with ACE activity in plasma and positively related with ACE activity in aorta and kidney. ACE activity in plasma significantly increased after the long-term treatment with hEW (0.5 g/kg/day). ACE activity in aorta and kidney was significantly inhibited 4 h after the short-term administration of hEW. The long-term treatment with hEW caused local effects on ACE activity in aorta, kidney and lungs that followed a pattern similar, but less pronounced, than that caused by captopril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Captopril; Diet; Egg White; Hydrolysis; Hypertension; Kidney; Lung; Male; Pepsin A; Peptidyl-Dipeptidase A; Rats; Rats, Inbred SHR

This paper evaluates the effect of the long-term intake of a hydrolysate of egg white with pepsin (HEW), with a potent angiotensin converting enzyme inhibitory activity, on the development of hypertension of spontaneously hypertensive rats (SHR). After being weaned, male 3-week-old SHR were randomly divided into five groups that were given until the 20th week of life the following drinking fluids: (1) tap water, (2) non-treated egg white 1 g/kg/day, (3) captopril 100 mg/kg/day, (4) HEW 0.5 g/kg/day, and (5) HEW 1 g/kg/day. From the 20th to 25th week of life, animals from all groups were given tap water. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured weekly in the rats, from the 6th to 25th week of life, by the tail cuff method. Development of hypertension was attenuated in the groups treated with captopril and HEW (P<0.001 vs. the group that drunk tap water). At the 20th week of life, the arterial blood pressure values of the different groups of rats were: tap water (SBP = 219.5 +/- 5.7, DBP = 167 +/- 3.7), non-treated egg white (SBP = 206.4 +/- 1.43, DBP = 166.4 +/- 4.9), captopril (SBP = 131.7 +/- 2.74, DBP = 91.5 +/- 1.62), HEW 0.5 g/kg/day (SBP = 182.9 +/- 4.64, DBP = 127.5 +/- 2.1) and HEW 1 g/kg/day (SBP = 177.7 +/- 4.72, DBP = 120.1 +/- 2.4). SBP and DBP increased in the treated SHR when the corresponding antihypertensive treatment was removed. In spite of this, SBP remained lower in the SHR that had received captopril and HEW than in the SHR of the control groups (P<0.05). The present results suggest that HEW could be used as a functional food with antihypertensive activity.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Dose-Response Relationship, Drug; Egg White; Hypertension; Male; Protein Hydrolysates; Rats; Rats, Inbred SHR; Time Factors

In the present study we evaluate the blood pressure-lowering effect of the following products: the hydrolysate obtained from egg white (EW) by enzymatic treatment with pepsin (HEW), the peptide fraction of HEW with molecular mass lower than 3000 Da (HEW<3000 Da), and three peptide sequences isolated from HEW<3000 Da (Tyr-Ala-Glu-Glu-Arg-Tyr-Pro-Ile-Leu: YAEERYPIL); (Arg-Ala-Asp-His-Pro-Phe-Leu: RADHPFL); and (Ile-Val-Phe (IVF)). These peptides, and also HEW and HEW<3000 Da, had been characterized previously in vitro as potent inhibitors of angiotensin-converting enzyme (ACE). EW and the products mentioned earlier were orally administered by gastric intubation, to 17-20-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. We measured the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats by the tail cuff method before administration and also 2, 4, 6, 8 and 24 h post-administration. Distilled water served as negative control, and we used captopril (50 mg/kg) as positive control to carry out similar experiments with a known ACE inhibitor. HEW, HEW<3000 Da and the three peptide sequences decreased SBP and DBP in SHR but they did not modify these variables in WKY rats. The peptide sequences YAEERYPIL, RADHPFL and IVF showed a potency to decrease blood pressure greater than HEW or HEW<3000 Da. The results obtained suggest that the studied products could be used as a functional food with potential therapeutic benefit in the prevention and treatment of hypertension.

Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Dose-Response Relationship, Drug; Egg Proteins, Dietary; Egg White; Hypertension; Male; Molecular Weight; Peptide Fragments; Protein Hydrolysates; Rats; Rats, Inbred SHR; Rats, Inbred WKY