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Food Chemistry Nov 2023Angiotensin-I-converting enzyme (ACE) inhibitory activity and salt-reduction properties of umami peptides identified in chicken soup were investigated. The ACE...
Angiotensin-I-converting enzyme (ACE) inhibitory activity and salt-reduction properties of umami peptides identified in chicken soup were investigated. The ACE inhibition rate of TPLVDR (91.22%) and AEINKILGN (81.26%) was significantly higher than other umami peptides, and their semi-inhibitory concentration was 0.017 mM and 0.034 mM, respectively. After in vitro digestion, the inhibitory activity of AEINKILGN and TPLVDR decreased, but the original sequences were still detected. The docking results showed that AEINKILGN and TPLVDR mainly interacted with Zn and key sites (His353, Lys511and Glu411) in the active pockets of ACE through hydrogen bonds, which was crucial to the ACE inhibitory activity. Based on response surface methodology and sensory analysis, saltiness and palatability models were established to investigate the salt-reduction effect. The optimal level of AEINKILGN was about 1.16 mg/mL in 0.44% salt solution. And the TPLVDR was applicable to the low salt solution (0.1-0.2%) at a concentration from 0.23 to 0.29 mg/mL.
Topics: Animals; Angiotensin-Converting Enzyme Inhibitors; Chickens; Molecular Docking Simulation; Peptidyl-Dipeptidase A; Peptides; Sodium Chloride, Dietary; Sodium Chloride
PubMed: 37276669
DOI: 10.1016/j.foodchem.2023.136480 -
Journal of Microbiology, Immunology,... Dec 2023SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an...
BACKGROUND
SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an inflammatory process. Angiotensin-(1-7) may have an anti-inflammatory effect through activation of Mas receptor. This study aims to investigate whether SARS-CoV-2 SP can induce inflammation through ACE2 in the alveolar epithelial cells which can be modulated through angiotensin-(1-7)/Mas receptor axis.
METHODS
HPAEpiC were treated with SARS-CoV-2 SP in the presence or absence of ACE2 antagonist-dalbavancin and Mas receptor agonist-angiotensin-(1-7). Proinflammatory cytokine production (IL-6 and IL-8) were measured at mRNA and protein levels. MAP kinase phosphorylation and transcription factor activation was determined by Western Blot. Mas receptor was blocked by either antagonist (A779) or knockdown (specific SiRNA). Experiments were replicated using A549 cells.
FINDINGS
SARS-CoV-2 SP (5 μg/mL) significantly induced MAP kinase (ERK1/2) phosphorylation, downstream transcription factor (activator protein-1, AP-1) activation and cytokine production (IL-6 and IL-8) at both mRNA and protein levels. Pretreatment with dalbavancin (10 μg/mL), or angiotensin-(1-7) (10 μM) significantly reduced ERK1/2 phosphorylation, AP-1 activation, and cytokine production. However, these angiotensin-(1-7)-related protective effects were significantly abolished by blocking Mas receptor with either antagonist (A799,10 μM) or SiRNA knockdown.
INTERPRETATION
SARS-CoV-2 SP can induce proinflammatory cytokine production, which can be inhibited by either ACE2 antagonist or Mas receptor agonist-angiotensin-(1-7). Angiotensin-(1-7)-related protective effect on cytokine reduction can be abolished by blocking Mas receptor. Our findings suggest that ACE2/angiotensin-(1-7)/Mas axis may serve as a therapeutic target to control inflammatory response triggered by SARS-CoV-2 SP.
Topics: Humans; Alveolar Epithelial Cells; Angiotensin-Converting Enzyme 2; COVID-19; Cytokines; Interleukin-6; Interleukin-8; Peptidyl-Dipeptidase A; RNA, Messenger; RNA, Small Interfering; RNA, Viral; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Transcription Factor AP-1
PubMed: 37802686
DOI: 10.1016/j.jmii.2023.09.003 -
Foods (Basel, Switzerland) Nov 2023Hypertension is a widespread health risk, affecting over a billion people and causing 9 million deaths per year. The Renin-Angiotensin-Aldosterone System (RAAS) is a...
Hypertension is a widespread health risk, affecting over a billion people and causing 9 million deaths per year. The Renin-Angiotensin-Aldosterone System (RAAS) is a primary target for hypertension treatment, and it is primarily treated through drugs that inhibit the Angiotensin I-Converting Enzyme (ACE). In addition to pharmacological treatment, various plants are recommended in traditional medicine for blood pressure regulation. This study aimed to produce high-phenolic-content extracts with and without enzymatic assistance from red grape pomace and evaluate their antioxidant capacity and ACE inhibitory potential. The total phenolic content (TPC) was measured, and phenolic identification was performed using HPLC analysis. In addition, the antioxidant capacity and anti-hypertensive potential were determined via in vitro assays. There was no statistical difference in the TPC antioxidant capacity between the extraction methods. Otherwise, when considering the extraction yield, the enzymatic process recovered around 70% more phenolic compounds from the pomace, and the phenolic profile was changed. Enzymatic assistance also significantly increased the ACE inhibitory potential in the grape pomace extract. This study demonstrates the viability of upcycling grape pomace to obtain bioactive compounds and to reduce their environmental impact, and highlights the influence of the enzymatic extraction on the hypotensive potential of the extract.
PubMed: 38002167
DOI: 10.3390/foods12224109 -
Food & Function Sep 2023Donkey colostrum, due to its abundance of active ingredients, including lysozyme, proteins, and peptides, is essential for the growth and immune defence of newborns....
Donkey colostrum, due to its abundance of active ingredients, including lysozyme, proteins, and peptides, is essential for the growth and immune defence of newborns. However, research on endogenous peptides in donkey colostrum is inadequate. This study analysed the profiles of endogenous peptides, their potential bioactivity, and the enzymes that generated these peptides using two different strategies. A total of 6202 endogenous peptides were characterised through a database search, while an additional 2997 peptides were identified . Among the 1142 proteins identified, trypsin and plasmin demonstrated the highest bioactivities. Furthermore, a bioinformatics-based screening identified antioxidant peptides, angiotensin I-converting enzyme inhibitory peptides, and dipeptidyl peptidase IV inhibitory peptides as the three most active peptides. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted. These findings enhance our knowledge of endogenous peptides in donkey colostrum and provide crucial information regarding these peptides as nutritional factors for the future development of functional foods derived from donkey sources.
Topics: Female; Pregnancy; Humans; Colostrum; Peptides; Fibrinolysin; Antioxidants; Computational Biology
PubMed: 37602399
DOI: 10.1039/d3fo01703f -
Frontiers in Endocrinology 2023Twin gestation is related to a higher risk of hypertensive disorders in pregnancy with possible risk stratification depending on chorionicity. It may be related to... (Observational Study)
Observational Study
INTRODUCTION
Twin gestation is related to a higher risk of hypertensive disorders in pregnancy with possible risk stratification depending on chorionicity. It may be related to differences in plasma renin-angiotensin-aldosterone components between monochorionic and dichorionic twin pregnancies. The study aimed to analyze the plasma ANG II and ANG 1-7 concentrations in women with monochorionic and dichorionic twin gestation.
METHODS
A prospective observational study included 79 women between 32 and 34 weeks of gestation with twin pregnancy (31 with monochorionic gestation and 48 with dichorionic gestation). Angiotensin II and angiotensin 1-7 concentrations were measured in the collected blood samples.
RESULTS
No significant differences were observed in angiotensin II concentrations between the dichorionic and monochorionic group with significantly higher levels of angiotensin 1-7 being observed in the dichorionic group. Angiotensin 1-7 level was higher than angiotensin II in 20 women (64.5%) in the monochorionic group and in 42 women (87.5%, p=0.01) in the dichorionic group. Higher plasma concentrations of angiotensin II and lower concentrations of angiotensin 1-7 were found in 5 women with gestational hypertension and in 3 with preeclampsia compared to normotensive women.
DISCUSSION
It is the first study investigating angiotensin II and angiotensin 1-7 in twin pregnancies regarding chorionicity. Our results showed that plasma angiotensin 1-7 concentration was related to chorionicity, while plasma angiotensin II level was not. In most women with twin gestation angiotensin 1-7 concentration exceeded the concentration of angiotensin II. A switch in the relation between angiotensin II and angiotensin 1-7 was observed in hypertensive pregnant women.
Topics: Pregnancy; Female; Humans; Pregnancy, Twin; Angiotensin II; Pregnancy Trimester, Third; Peptide Hormones; Hypertension, Pregnancy-Induced; Angiotensin I; Peptide Fragments
PubMed: 38260128
DOI: 10.3389/fendo.2023.1329025 -
European Journal of Pharmacology Jan 2024Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disease characterized by diffuse alveolar inflammation, fibroblast differentiation, and the excessive...
Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disease characterized by diffuse alveolar inflammation, fibroblast differentiation, and the excessive deposition of extracellular matrix. During the progression of PF, redox imbalance caused by excessive reactive oxygen species (ROS) production can result in further destruction of lung tissue. At present, data on the role of NADPH oxidase-4 (Nox4)-nuclear factor erythroid 2-related factor 2 (Nrf2) redox imbalance in PF are limited. The angiotensin (1-7) [Ang-(1-7)]/Mas axis is a protective axis in the renin-angiotensin system (RAS) that exerts antifibrotic effects. Therefore, this study aimed to investigate the role of the Ang-(1-7)/Mas axis in PF and to explore its mechanism in depth. The results revealed that the Ang-(1-7)/Mas axis inhibited TGF-β1-induced lung fibroblast differentiation, inflammation and fibrosis in bleomycin (BLM)-treated lung tissue. A mechanistic study suggested that the Ang-(1-7)/Mas axis may restore Nox4-Nrf2 redox homeostasis by upregulating the level of p62, reducing oxidative stress and the inflammatory response and thus delaying the progression of lung fibrosis. This study provides a theoretical basis for exploring the mechanisms of PF and therapeutic targets for PF.
Topics: Mice; Animals; Pulmonary Fibrosis; NF-E2-Related Factor 2; Bleomycin; Peptidyl-Dipeptidase A; Lung; Inflammation; Oxidation-Reduction; Homeostasis; NADPH Oxidase 4
PubMed: 38043775
DOI: 10.1016/j.ejphar.2023.176233 -
Molecules (Basel, Switzerland) Oct 2023Angiotensin-converting enzyme 1 (ACE1) is a peptide involved in fluid and blood pressure management. It regulates blood pressure by converting angiotensin I to...
Detection of Various Traditional Chinese Medicinal Metabolites as Angiotensin-Converting Enzyme Inhibitors: Molecular Docking, Activity Testing, and Surface Plasmon Resonance Approaches.
Angiotensin-converting enzyme 1 (ACE1) is a peptide involved in fluid and blood pressure management. It regulates blood pressure by converting angiotensin I to angiotensin II, which has vasoconstrictive effects. Previous studies have shown that certain compounds of natural origin can inhibit the activity of angiotensin-converting enzymes and exert blood pressure-regulating effects. Surface Plasmon Resonance (SPR) biosensor technology is the industry standard method for observing biomolecule interactions. In our study, we used molecular simulation methods to investigate the docking energies of various herbal metabolites with ACE1 proteins, tested the real-time binding affinities between various herbal metabolites and sACE1 by SPR, and analyzed the relationship between real-time binding affinity and docking energy. In addition, to further explore the connection between inhibitor activity and real-time binding affinity, several herbal metabolites' in vitro inhibitory activities were tested using an ACE1 activity test kit. The molecular docking simulation technique's results and the real-time affinity tested by the SPR technique were found to be negatively correlated, and the virtual docking technique still has some drawbacks as a tool for forecasting proteins' affinities to the metabolites of Chinese herbal metabolites. There may be a positive correlation between the enzyme inhibitory activity and the real-time affinity detected by the SPR technique, and the results from the SPR technique may provide convincing evidence to prove the interaction between herbal metabolites and ACE1 target proteins.
Topics: Angiotensin-Converting Enzyme Inhibitors; Molecular Docking Simulation; Surface Plasmon Resonance; Biosensing Techniques; Angiotensins
PubMed: 37894610
DOI: 10.3390/molecules28207131 -
Clinical Science (London, England :... Aug 2023An unbalance in the renin-angiotensin (Ang) system (RAS) between the Ang II/AT1 and Ang-(1-7)/Mas axis appears to be involved in preeclampsia (PE), in which a reduction...
BACKGROUND
An unbalance in the renin-angiotensin (Ang) system (RAS) between the Ang II/AT1 and Ang-(1-7)/Mas axis appears to be involved in preeclampsia (PE), in which a reduction in Ang-(1-7) was observed. Here, we tested whether the reduction in the activity of the Ang-(1-7)/Mas axis could be a contributing factor for the development of PE, using Mas-deficient (Mas-/-) mice.
METHODS AND RESULTS
Cardiovascular parameters were evaluated by telemetry before, during pregnancy and 4 days postpartum in 20-week-old Mas-/- and wild-type (WT) female mice. Mas-/- mice presented reduced arterial blood pressure (BP) at baseline (91.3 ± 0.8 in Mas-/- vs. 94.0 ± 0.9 mmHg in WT, Diastolic, P<0.05). However, after the 13th day of gestation, BP in Mas-/- mice started to increase, time-dependently, and at day 19 of pregnancy, these animals presented a higher BP in comparison with WT group (90.5 ± 0.7 in Mas-/- vs. 80.3 ± 3.5 mmHg in WT, Diastolic D19, P<0.0001). Moreover, pregnant Mas-/- mice presented fetal growth restriction, increase in urinary protein excretion as compared with nonpregnant Mas-/-, oliguria, increase in cytokines, endothelial dysfunction and reduced ACE, AT1R, ACE2, ET-1A, and eNOS placental mRNA, similar to some of the clinical manifestations found in the development of PE.
CONCLUSIONS
These results show that Mas-deletion produces a PE-like state in FVB/N mice.
Topics: Pregnancy; Female; Mice; Animals; Humans; Peptidyl-Dipeptidase A; Proto-Oncogene Proteins; Proto-Oncogene Mas; Pre-Eclampsia; Placenta; Renin-Angiotensin System; Receptors, G-Protein-Coupled; Angiotensin II; Phenotype; Angiotensin I; Peptide Fragments
PubMed: 37527493
DOI: 10.1042/CS20220819 -
Plant Foods For Human Nutrition... Mar 2024Angiotensin I-converting enzyme (ACE)-inhibiting peptides were isolated from walnut protein isolate (WPI) using ultrasound-assisted extraction. This study aimed to...
Screening and Constructing of Novel Angiotensin I-Converting Enzyme Inhibiting Peptides from Walnut Protein Isolate and Their Mechanisms of Action: A Merged In Silico and In Vitro Study.
Angiotensin I-converting enzyme (ACE)-inhibiting peptides were isolated from walnut protein isolate (WPI) using ultrasound-assisted extraction. This study aimed to assess the impact of ultrasonic pretreatment on the physicochemical properties of WPI. The optimal extraction conditions for WPI were determined as a 15-min ultrasonic treatment at 400 W. Subsequently, the hydrolysate exhibiting the highest in vitro ACE-inhibiting activity underwent further processing and separation steps, including ultrafiltration, ion exchange chromatography, liquid chromatography-tandem mass spectrometry, ADMET screening, and molecular docking. As a result of this comprehensive process, two previously unidentified ACE-inhibiting peptides, namely Tyr-Ile-Gln (YIQ) and Ile-Tyr-Gln (IYQ), were identified. In addition, a novel peptide, Ile-Lys-Gln (IKQ), was synthesized, demonstrating superior ACE-inhibiting activity and temperature stability. In silico analysis estimated an in vivo utilization rate of 21.7% for IKQ. These peptides were observed to inhibit ACE through an anti-competitive mechanism, with molecular docking simulations suggesting an interaction mechanism involving hydrogen bonding. Notably, both IYQ and IKQ peptides exhibited no discernible toxicity to HUVECs cells and promoted nitric oxide (NO) generation. These findings underscore the potential of ultrasonicated WPI in the separation of ACE-inhibiting peptides and their utility in the development of novel ACE inhibitors for functional food applications.
Topics: Juglans; Peptidyl-Dipeptidase A; Molecular Docking Simulation; Peptides; Angiotensin-Converting Enzyme Inhibitors; Protein Hydrolysates
PubMed: 37962805
DOI: 10.1007/s11130-023-01122-1 -
International Journal of Molecular... Dec 2023Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling...
Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling processes that lead to right-ventricular heart failure and, ultimately, death. Although our understanding of its pathophysiology has advanced and several treatment modalities are currently available for the management of PAH patients, none are curative and the prognosis remains poor. Therefore, further research is required to decipher the molecular mechanisms associated with PAH. Angiotensin-converting enzyme 2 (ACE2) plays an important role through its vasoprotective functions in cardiopulmonary homeostasis, and accumulating preclinical and clinical evidence shows that the upregulation of the ACE2/Angiotensin-(1-7)/MAS1 proto-oncogene, G protein-coupled receptor (Mas 1 receptor) signaling axis is implicated in the pathophysiology of PAH. Herein, we highlight the molecular mechanisms of ACE2 signaling in PAH and discuss its potential as a therapeutic target.
Topics: Humans; Pulmonary Arterial Hypertension; Angiotensin-Converting Enzyme 2; Hypertension, Pulmonary; Peptidyl-Dipeptidase A; Familial Primary Pulmonary Hypertension; Receptors, G-Protein-Coupled; Angiotensin I; Peptide Fragments; Renin-Angiotensin System
PubMed: 38139269
DOI: 10.3390/ijms242417441