Angiotensin I-converting Enzyme Activity Research Articles

The Pharmacogenetic Footprint of ACE Inhibition: A Population-Based Metabolomics Study.

Angiotensin-I-converting enzyme (ACE) inhibitors are an important class of antihypertensives whose action on the human organism is still not fully understood. Although it is known that ACE especially cleaves COOH-terminal dipeptides from active polypeptides, the whole range of substrates and products is still unknown. When analyzing the action of ACE inhibitors, effects of genetic variation on metabolism need to be considered since genetic variance in the ACE gene locus was found to be associated with ACE-concentration in blood as well as with changes in the metabolic profiles of a general population. To investigate the interactions between genetic variance at the ACE-locus and the influence of ACE-therapy on the metabolic status we analyzed 517 metabolites in 1,361 participants from the KORA F4 study. We replicated our results in 1,964 individuals from TwinsUK. We observed differences in the concentration of five dipeptides and three ratios of di- and oligopeptides between ACE inhibitor users and non-users that were genotype dependent. Such changes in the concentration affected major homozygotes, and to a lesser extent heterozygotes, while minor homozygotes showed no or only small changes in the metabolite status. Two of these resulting dipeptides, namely aspartylphenylalanine and phenylalanylserine, showed significant associations with blood pressure which qualifies them—and perhaps also the other dipeptides—as readouts of ACE-activity. Since so far ACE activity measurement is substrate specific due to the usage of only one oligopeptide, taking several dipeptides as potential products of ACE into account may provide a broader picture of the ACE activity.

Wine pomace seasoning attenuates hyperglycaemia-induced endothelial dysfunction and oxidative damage in endothelial cells

Dietary antioxidants such as phenolic phytochemicals may prevent/improve endothelial function impairment observed in cardiovascular diseases. This study investigates the specific protective effects of a vegetal seasoning obtained from seedless wine pomace against hyperglycaemia-induced oxidative damage and dysfunction in human umbilical vein endothelial cells EA.hy926. Non-cytotoxic doses of the bioactive compounds obtained following in vitro digestion of the seasoning were used as treatments. Digested compounds, especially colonic bacterial metabolites, restored a more balanced redox environment, prevented lipid peroxidation and cell membrane damage, ameliorated protein oxidation, and improved the balance between endothelial reactive oxygen species and nitric oxide production in hyperglycaemic cells. Reduction of angiotensin I-converting enzyme activity and gene modulation of superoxide dismutase, haem oxygenase-1, β-nicotinamide adenine dinucleotide phosphate oxidase-4, and endothelial nitric oxide synthase are proposed as the mechanisms underlying this protection. These results support the potential benefits of functional wine pomace seasonings in vascular complications associated with oxidative stress.

Identification of four new angiotensin I-converting enzyme inhibitory peptides from fermented anchovy sauce

The inhibitory activity of an angiotensin I-converting enzyme (ACE), a key regulatory enzyme of blood pressure from the fermented anchovy sauce, was evaluated, and ACE inhibitory peptides were purified. The ACE activity significantly increased with an increase in salt concentration. In addition, the ACE inhibitory activity of the fermented anchovy sauce containing high salt content (25 %) significantly increased with an increase in fermentation time. The maximum activity (96 %) was reached after 15 months of fermentation. Four ACE inhibitors [Pro-Lys (PK), Gly-Cys-Lys (GCK), Asn- His-Pro (NHP), and Asp-Gly-Gly-Pro (DGGP)] in the fermented anchovy sauce were purified through various chromatographic techniques and identified by electrospray ionization tandem mass spectrometer analysis. Four newly identified peptides were synthesized and analyzed for ACE inhibitory activity in order to confirm that the purified peptides were actually ACE inhibitors. The IC50 values for ACE inhibitory activities of synthesized peptides DGGP, GCK, NHP, and PK were 164, 178, 1172, and 4092 μM, respectively.

Importance of ACE polymorphisms for endurance performance

The skeletal muscle renin-angiotensin system (RAS) plays an important role in exercise metabolism. A functional insertion (I)/deletion (D) polymorphism in the angiotensin I- converting enzyme (ACE) gene (rs4646994) has been associated with ACE activity. The ACE DD genotype is associated with increased circulating ACE levels, which are generally two times as high as those found for II genotypes. Although most reports suggest that the I allele predisposes to human endurance (1) the literature also contains some opposite data (2). These inconsistencies from genetic association studies relating to the ACE gene and its I/D polymorphism maybe attributable, partially, to epigenetic factors that have been reported to influence ACE activity. Indeed, if both copies of the ACE D/D gene are transiently methylated, ACE increased levels associated with this polymorphism, may be down-regulated. However, there have not been any reports that address whether epigenetic regulation of the ACE gene is specifically involved in modifying human endurance, but, importantly, the human ACE gene promoter has been shown to harbor CpG islands. It is well established that environmental factors may modify the epigenetic profile and that nutrition training, muscle unloading and mechanical stimulation significantly impact on performance, playing an epigenetic role . Hence, it is conceivable that some of these factors might influence the CpG islands within the ACE promoter affecting its expression. The present study is aimed at modulating the epigenetic pattern of the ACE promoter by administering arginine to professional soccer players. ACE (DD, ID, and II) will be genotyped by PCR, then the epigenetic profile of ACE (gene promoter methylation) will be determined by bisulfite method, the serum levels of angiotensin 2 will be measured by ELISA. Hence, we compare the performance capacity of soccer players exhibiting different ACE polymorphisms, by strength, speed, and endurance tests. Subsequently, we will split the subjects under study in 2 groups: group 1 will follow a mediterrean diet, group 2 will follow the same mediterrean diet supplemented with arginine. After six months we will analyze if an epigenetic regulation of the ACE gene has occurred, modulating endurance performance.

ACE insertion/deletion polymorphism and restenosis events after coronary stent placement in East Azerbaijan Province of Iran

Renin-angiotensin system is thought to play a role in coronary thrombosis and restenosis. Plasma angiotensin I-converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. The association among restenosis within coronary stents, the D/I polymorphism is analyzed in the present study. We are selected 50 patients who had undergone successful percutaneous transluminal coronary angioplasty, and angiography during 1 year after it for some reason. The I/D alleles were identified on the basis of polymerase chain reaction (PCR) amplification of the respective fragments from intron 16 of ACE gene. The differences between groups were tested by Chi-square test or Fisher exact test. Result from chi-square test and Fisher exact test shows the lack of differences between two groups with respect to sex, age, diabetes, hypertension, cholesterol, hyperlipidemia, stent type, length of stented segment, stent diameter and target vessel. In the second set of analysis, the relationship between genotypes and the outcome variable was tested. These analyses indicated that there were no statistically significant differences the three groups (χ2 (2) = 1.40, p=0 .47). The ACE D/D genotype or D allele does not influence the clinical and angiographic outcome of patients undergoing coronary stent placement. These data suggest that routine determination of the ACE genotype may not help identify patients who are at a higher risk of thrombotic and restenosis events after coronary stent placement.

Identification of active substances for dually modulating the renin–angiotensin system in Bidens pilosa by liquid chromatography–mass spectrometry–based chemometrics

Bidens pilosa is used as a functional food and a traditional Chinese medicine to treat hypertensive disease. In this study, based on a bioactivity-guided fractionation of renin- and angiotensin I-converting enzyme (ACE)-inhibitory activities, a method of liquid chromatography–mass spectrometry (LC–MS)-based chemometrics analysis was used to identify bioactive compounds from the ethanol extract of B. pilosa. Polyphenol-containing fraction exhibited the highest dual inhibitions towards renin and ACE activities. A total 18 marker metabolites were positively or tentatively identified by LC–MS/MS, five of which contributed most to distinguishing between active and inactive portions and were confirmed to possess in vitro dual inhibitory activities against renin and ACE. This is the first study to demonstrate the active constituents of B. pilosa for dually regulating the renin–angiotensin system (RAS) in vitro. This established method represents a rapid and effective method for the identification of bioactive compounds from functional foods and nutraceuticals.

Do whey protein-derived peptides have dual dipeptidyl-peptidase IV and angiotensin I-converting enzyme inhibitory activities?

Inhibition of dipeptidyl-peptidase IV (DPP-IV) and angiotensin I-converting enzyme (ACE) are useful strategies for managing, respectively, diabetes and hypertension, two conditions often occurring together. In this study, debittered and non-debittered whey protein hydrolysates (WPHs) were assessed for their in vitro inhibitory activity against ACE and DPP-IV and characterized for their constituent peptides. All WPHs and several fractions obtained from them had ACE and DPP-IV inhibitory activities, with ACE being generally more strongly inhibited than DPP-IV. Among the identified peptides tested, GYGGVSLPEW derived from α-lactalbumin and LKPTPEGDLE from β-lactoglobulin were, respectively, the most effective at inhibiting ACE (IC50 = 2 µM) and DPP-IV (IC50 = 42 µM). Although some identified peptides were able to inhibit both enzymes, the majority did not show a dual inhibitory effect. This research provides new insight on the active peptides responsible for the ACE and DPP-IV inhibitory activities of whey protein hydrolysates.

Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia.

In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=−5.216; P<0.001). ACE activity significantly correlated to Hopkins delayed recall measures (r=−0.247; P=0.004) and Hopkins total (r=−0.214; P=0.012). Subjects grouped as high ACE activity (above average) had worse performance compared with low ACE activity level group for Hopkins delayed recall measure, even after correction for clinical condition, age, gender and years of education (P=0.029). The adjusted R squared for this final model was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (P<0.05) compared with two copies of wild-type animals. The results observed in SCZ patients and animal model suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations.

Kinetics of in vitro enzyme inhibition and blood pressure-lowering effects of salmon (Salmo salar) protein hydrolysates in spontaneously hypertensive rats

A salmon protein hydrolysate (SPH) was produced from consecutive enzymatic hydrolysis of salmon muscle proteins with pepsin followed by trypsin + chymotrypsin. The SPH was separated into four (SF1-SF4) reverse-phase HPLC peptide fractions. The SF3 peptide fraction was the most active against both angiotensin I-converting enzyme (ACE) and renin activities during in vitro tests. SPH and SF3 inhibited ACE activity uncompetitively but renin inhibition was non-competitive. SPH and SF3 were orally administered (200 and 30 mg/kg body weight, respectively) to spontaneously hypertensive rats, followed by systolic blood pressure (SBP) measurements. The SF3 significantly (p < 0.05) reduced SBP by a maximum value of −42.1 ± 3.4 mmHg when compared to −21.1 ± 4.5 mmHg for SPH 2 h after oral administration. Mass spectrometry analysis showed some differences in the peptide ion composition, which may have contributed to the observed differences in SBP-reducing effects of SPH and SF3.

A comparative study on antihypertensive and antioxidant properties of phenolic extracts from fruit and leaf of some guava (Psidium guajava L.) varieties

Investigation of antihypertensive and antioxidant properties of fruit and leaf extracts from four varieties (giant white, small white, stripped and pink) of guava (Psidium guajava L.) in vitro was the focus of this study. Consequently, methanol/1 M HCl (20:1 v/v) extraction of fruit and leaf of the guava varieties were carried out. Thereafter, the extracts were assayed for their angiotensin I converting enzyme (ACE) inhibitory effect, total phenol and flavonoid contents, reducing property, radicals (DPPH, ABTS•+, hydroxyl and nitric oxide) scavenging ability, Fe2+ chelating ability, and inhibition of Fe2+ and Sodium nitroprusside (SNP) induced lipid peroxidation reactions (in vitro). Furthermore, the phenolic constituents of the extracts were characterised with gas chromatography (GC). The results showed that all the extracts significantly (P < 0.05) inhibited ACE activity, scavenged (DPPH, ABTS•+, nitric oxide and hydroxyl) radicals, chelated Fe2+ and also inhibited Fe2+ and SNP induced lipid peroxidation in rat heart (in vitro). Nevertheless, the pink guava variety had the highest ACE inhibitory and antioxidant properties. In addition, Rosmarinic acid, eugenol, carvacrol, catechin and caffeic acid were the dominant phenolics found in the extracts. The ACE inhibitory effects and antioxidant properties of the guava extracts, which correlates significantly with their phenolic constituents, could largely contribute to their antihypertensive properties as obtained in traditional medicine.

Impact of Elicitation on Antioxidant and Potential Antihypertensive Properties of Lentil Sprouts

The aim of this study was to investigate the application of elicitors (500 μM ascorbic acid, 50 μM folic acid, 5 mM glutamic acid and 50 ppm chitosan in 5 mM glutamic acid) during lentil germination up to 8 days as a strategy to increase germination rate and to enhance the accumulation of γ-aminobutyric acid (GABA) and phenolic compounds. The effect of elicitation on the protein profile and antioxidant and angiotensin I converting enzyme (ACE) inhibitory activities of sprouted lentils was also evaluated. The application of elicitors did not negatively affect the germination yield of lentils and no significant changes on the protein pattern of lentils germinated in the presence of elicitors were observed. Chitosan/glutamic acid increased by 1.6-fold the GABA content in lentil sprouts, whilst ascorbic and folic acids as well as chitosan/glutamic acid were highly effective to enhance the total content of phenolic compounds and the antioxidant activity of sprouted lentils. All elicited lentil sprouts showed ability to inhibit ACE activity (IC50: 9.5-11.9 μg peptides/mL). Therefore, elicitation can be considered a promising approach to improve the content of compounds with antioxidant and potential antihypertensive activities in lentil sprouts.

Purification and identification of antioxidant and ACE-inhibitory peptide from Saccharomyces cerevisiae protein hydrolysate

Yeast protein hydrolysate may be considered as a good source of bioactive peptides. Yeast hydrolysate was prepared by two different physical-enzymatic and autolysis treatments to identify the most active angiotensin I-converting enzyme (ACE) inhibitory and antioxidant peptides. The most active hydrolysate was obtained after sonication-trypsin hydrolysis. The hydrolysate was subjected to fractionation by ultrafiltration. Fraction with molecular weight of <3 kDa exhibited the highest activity. Reverse phase high performance liquid chromatography (RP-HPLC) resolved this fraction into five fractions, one of which (fraction F3) with amino acid sequence of Tyr-Gly-Lys-Pro-Val-Ala-Val-Pro-Ala-Arg (MW:1057.45 Da) exhibited ACE inhibitory (IC50 = 0.42 ± 0.02 mg/ml) and antioxidant activities (26.25 ± 0.13 µM TE/µg protein). Taken together, the results of this study show that S. cerevisiae proteins contain specific peptides in their sequences which can be released by enzymatic hydrolysis. These peptides have excellent bioactive properties that can potentially replace the antioxidant and antihypertensive agents with chemical origin.

Effects of Metabolites Produced from (-)-Epigallocatechin Gallate by Rat Intestinal Bacteria on Angiotensin I-Converting Enzyme Activity and Blood Pressure in Spontaneously Hypertensive Rats.

Inhibitory activity of angiotensin I-converting enzyme (ACE) was examined with (-)-epigallocatechin gallate (EGCG) metabolites produced by intestinal bacteria, together with tea catechins. All of the metabolites showed ACE inhibitory activities and the order of IC50 was hydroxyphenyl valeric acids > 5-(3,4,5-trihydroxyphenyl)-γ-valerolactone (1) > trihydroxyphenyl 4-hydroxyvaleric acid ≫ dihydroxyphenyl 4-hydroxyvaleric acid ≫ 5-(3,5-dihydroxyphenyl)-γ-valerolactone (2). Among the catechins, galloylated catechins exhibited stronger ACE inhibitory activity than nongalloylated catechins. Furthermore, the effects of a single oral intake of metabolites 1 and 2 on systolic blood pressure (SBP) were examined with spontaneously hypertensive rats (SHR). Significant decreases in SBP were observed between 2 h after oral administration of 1 (150 mg/kg in SHR) and the control group (p = 0.002) and between 4 h after administration of 2 (200 mg/kg in SHR) and the control group (p = 0.044). These results suggest that the two metabolites have hypotensive effects in vivo.

Screening, discovery, and characterization of angiotensin-I converting enzyme inhibitory peptides derived from proteolytic hydrolysate of bitter melon seed proteins

In this study, new angiotensin-I converting enzyme (ACE) inhibitory peptides were comprehensively identified from a thermolysin digest of bitter melon (Momordica charantia) seed proteins. The hydrolysate was fractionated by reversed-phase high performance liquid chromatography (RP-HPLC), and the inhibitory activities of the resulting fractions were evaluated using ACE inhibitory assay. Two novel ACE inhibitory peptides (VY-7 and VG-8) were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and database-assisted peptide sequencing. VY-7 and VG-8 were derived from momordin A and MAP30, respectively, and their IC50 values were as low as 8.64±0.60 and 13.30±0.62μM, respectively. Lineweaver–Burk plots further indicated that VY-7, which showed the best IC50 value, acts as a competitive inhibitor. Notably, the content of VY-7 in crude thermolysin digest was determined to be as high as 14.89±0.88μg/mg using LC-MS/MS quantification. In the spontaneously hypertensive rat (SHR) model, oral administration of VY-7 at 2mg/kg body weight significantly decreased the systolic blood pressure. The interaction between VY-7 and ACE was examined using molecular docking calculations and the results suggested that certain residues of VY-7 can fit perfectly into the S1, S1’ and S2’ regions of the binding pocket of ACE. Biological significanceOne of the most common supportive therapies for treating hypertension is the use of synthetic drugs to inhibit ACE activity. Synthetic ACE inhibitors possess good antihypertensive effects, but come with accompanying side effects. Therefore, food-derived ACE inhibitory peptides are regarded as safer alternatives and are attracting much attention for hypertension treatment. In this study, we comprehensively identified peptides derived from bitter melon (Momordica charantia) seed proteins (BMSPs) using a shotgun proteomics approach. Based on results from an in vitro ACE inhibitory assay, two peptides (VY-7 and VG-8) derived from momordin A and MAP30 proteins, respectively, showed good ACE inhibitory activities. For VY-7, which showed the best IC50 value (8.64±0.60μM), the inhibition type was determined to be competitive inhibition, as found using a Lineweaver–Burk plot. The novel ACE inhibitory peptide VY-7 (at 2mg/kg body weight) as well as the crude hydrolysate of BMSPs (at 10mg/kg body weight) showed significant and moderate antihypertensive effects, respectively, in an animal model of hypertension, spontaneously hypertensive rats (SHRs). The present work demonstrated the screening of ACE inhibitory peptides from BMSPs and, as far as we know, VY-7 is the first well-characterized antihypertensive peptide derived from bitter melon seeds.

A Novel ACE Inhibitory Peptide Ala-His-Leu-Leu Lowering Blood Pressure in Spontaneously Hypertensive Rats.

Ala-His-Leu-Leu (AHLL) was isolated and purified from the loach (Misgurnus anguillicaudatus) hydrolysate in our previous study. The aim of this study was to investigate the antihypertensive effects of angiotensin-I-converting enzyme (ACE) inhibitory peptide AHLL in spontaneously hypertensive rats (SHRs). AHLL showed good antihypertensive effects in SHRs during the long-term oral administration and no allergic reactions or coughing were observed. After 2 months of oral administration of AHLL, the body weight growth was normal. The decrements in systolic blood pressure of the high dose (5 mg/kg bw) and the low dose of AHLL (1 mg/kg bw) treatment groups were 22.1 and 5.0 mmHg at week 8, respectively. Compared to the control group, the concentrations of triglyceride and sodium in serum were reduced significantly in the high-dose group after 2 months. The ACE activity of kidney and lung decreased significantly, which indicated that AHLL exerted an antihypertensive effect on kidney and lung and they were the target sites of AHLL. These results strongly supported the in vivo antihypertensive mechanism of AHLL.

Angiotensin converting enzyme activity is positively associated with IL-17a levels in patients with schizophrenia

Previous studies of our group showed increased plasmatic Angiotensin-I Converting Enzyme (ACE) activity in schizophrenia (SCZ) patients compared to healthy controls, which was also associated to poor cognitive functioning. The ACE main product angiotensin II (Ang-II) has pro-inflammatory properties. Activated immune-inflammatory responses in SCZ and their association with disease progression and cognitive impairments are also well-described. Therefore, we examined here the association of plasma ACE activity and inflammatory mediators in 33 SCZ patients and 92 healthy controls. Non-parametric correlations were used to investigate the association of the enzyme activity and the peripheral levels of immune inflammatory markers as interleukins, tumor necrosis factor (TNF-α), and interferon (IFN-γ). Although no significant correlations could be observed for ACE activity and measured cytokines levels in healthy controls, a significant positive correlation for ACE enzymatic activity and IL-17a levels was observed in SCZ patients. Correcting for gender did not change these results. Moreover, a significant association for ACE activity and IFN-γ levels was also observed. To our knowledge, this is the first study to show a significant association between higher ACE activity and the levels of cytokines, namely IL-17a and IFN-γ, in patients with SCZ.

Characterization of the renal renin-angiotensin system in transgenic mice that express rat tonin.

Tonin is an enzyme that is able to generate angiotensin II (Ang II) from angiotensin I (Ang I) or directly from angiotensinogen. Our goal was to characterize the renal renin-angiotensin system in transgenic mice that express rat tonin (TGM`(rTon)). Mice were euthanized and the kidneys removed for analysis. Tonin activity was evaluated by radioimmunoassay and angiotensin I-converting enzyme (ACE) activity by HPLC. Tonin, ACE and angiotensin II-converting enzyme (ACE2) expression was analyzed by Western blotting. Tonin activity was significantly increased in TGM`(rTon) compared to their respective wild-type (WT) littermates (1.7 ± 0.21 vs 0.11 ± 0.02 nmol of Ang II/min/mg of protein). Tonin activity had a strong positive correlation with tonin expression in both TGM`(rTon) and their respective wild-type littermates. The ACE activity and expression levels of 65-kDa N-domain angiotensin I-converting enzyme isoform were significantly increased in the TGM`(rTon) when compared with WT. ACE2 expression levels were statistically significantly higher in the TGM`(rTon) when compared with WT. Angiotensin 1-7 (Ang(1-7)) and Ang I levels were significantly lower in the TGM`(rTon). We suggest that the environment of tonin abundance may increase N-domain ACE activity liberated by a secretase able to cleave somatic ACE.

Biological activities, antioxidant properties and phytoconstituents of essential oil from sweet basil (Ocimum basilicum L.) leaves

This study investigated the biological activities of essential oil from sweet basil leaves via its effect on α-amylase, α-glucosidase and angiotensin-I-converting enzyme (ACE) activities, inhibition of Fe2+ and sodium nitroprusside (SNP)-induced lipid peroxidation in rats’ pancreas and heart homogenates. The phytoconstituents of the oil were analysed using gas chromatography (GC). The essential oil exhibited a dose-dependent inhibition of α-amylase (IC50 = 3.21 mg/mL), α-glucosidase (IC50 = 3.06 mg/mL) and ACE (IC50 = 0.89 mg/mL) activities in vitro. The oil also inhibited both Fe2+- and SNP-induced lipid peroxidation in rats’ pancreas and heart. The GC analysis revealed the presence of about 28 phytoconstituents, with limonene (47.40 %), borneol (8.66 %), geranial (6.93 %), neral (5.71 %), myrcene (4.68 %), β-caryophyllene (4.68 %), α-terpineol (4.60 %), 1,8-cineole (4.17 %), linalool (3.53 %), β-elemene (3.05 %), germacrene D (2.68 %), and terpinen-4-ol (2.21 %) being the most prominent. Thus, the antioxidant and enzyme inhibitory effects of the essential oil could be attributed to the presence of these phytochemicals, which could be the principle responsible for the antidiabetic and antihypertensive properties of the essential oil. This study therefore, could provide the possible rationale for the application of essential oil from sweet basil leaves as functional foods and nutraceutical ingredient in the management of type 2 diabetes and hypertension.

In silico investigation of action mechanism of four novel angiotensin-I converting enzyme inhibitory peptides modified with Trp

To potentiate activities of angiotensin-I converting enzyme (ACE) inhibitory peptides VK, YA, KY and TAY from oyster hydrolysate, four novel tripeptides VKW, YAW, KYW and TAW were designed by modification with Trp at the C-terminus. The tripeptides were synthesized, and their 50% ACE inhibitory concentrations (IC50) were measured to be 0.020, 0.49, 0.43 and 0.63 µM, respectively. Their activities increased 27–1450 times compared to their corresponding original peptides. All peptides did not show toxicity on the Chang cell. Molecular docking and molecular dynamics simulation showed that modification with Trp can enhance the stability of ACE/derived peptide complexes by increasing binding affinity and interaction sites with important amino acid residues. Interactions between peptides with amino acid residues of ACE GLN281, ALA354, GLU411, PHE457 and LYS511 played an important role in activity improvement of derived peptides. Modification with Trp at the C-terminus was an effective way for designing novel ACE inhibitory peptides.

Nandrolone increases angiotensin-I converting enzyme activity in rats tendons

INTRODUCTION: The renin-angiotensin system (RAS) has been associated with several biological processes of the human body, regulating, among others blood pressure and water and electrolytes balance. Moreover, RAS also regulates connective tissue growth. Recently, studies have shown that the use of nandrolone modifies the angiotensin-I converting enzyme (ACE) activity and increases collagen deposition in the heart. OBJECTIVE: The aim of study was to evaluate the Angiotensin-I converting enzyme (ACE) activity in the superficial flexor tendon (SFT) and in serum after load exercise in combination with anabolic androgenic steroid (AAS) administration after training session and six weeks of detraining. METHODS: Forty-eight Wistar rats were used into two groups (G1 and G2) subdivided into four subgroups: Sedentary (S); trained (T); AAS-treated (Deca-Durabolin(r), 5mg/kg, twice a week) sedentary rats (AAS) and AAS-treated and trained animals (AAST). Trained groups performed jumps in water: four series of 10 jumps each, followed by a 30 sec interval between the series, for seven weeks. RESULTS: Training increased ACE activity in the SFT compared to the control group (p &lt;0.05). Both AAS and AAST groups presented higher ACE activity levels (p &lt; 0.05). The AAST increased the ACE activity only compared to the trained animals. Only the AAST group presented significant higher levels of ACE in the serum. In the G2 group, all experimental groups presented decreased ACE activity in the serum and in the tendon, as compared to the control group. CONCLUSION: This study indicates that AAS administration and its combination with exercise increased ACE activity of tendons. AAS abuse could compromise tendon adaptation causing maladaptive remodeling.