Angiotensin I-converting Enzyme Activity Research Articles

Inhibitory activity of Angiotensin-I converting enzyme (ACE-I) from partially purified Phaseolus lunatus peptide fractions

Phaseolus lunatus have proven to be a likely source of peptides with bioactivities that could be used to prevent and treat chronic degenerative diseases like arterial hypertension (AHT). Angiotensin-I converting enzyme (ACE-I) inhibition is essential for the AHT pathophysiology. In this work, the kinetic study of inhibition and inhibitory activity of ACE-I from peptide fractions partially purified from a protein hydrolysate from Phaseolus lunatus was performed. Hydrolysis was done by sequential enzymatic treatments with Pepsin-Pancreatin. The hydrolysates were ultrafiltered with 3 kDa and 5 kDa membranes, obtaining a fraction of 3–5 kDa which was later purified by gel filtration chromatography (GFC) and high-performance liquid chromatography (HPLC). The GFC fractions exhibited ACE-I inhibitory activities (ACE-I_I) up to 37.86% with an IC50 of 6.34 μg/mL. From HPLC purification, ACE-I_I up to 26.23% were obtained with an IC50 of 2.69 μg/mL. The kinetic parameters of the inhibition indicated that the peptides inhibit ACE-I through a competitive mechanism. The amino acids of the fractions evaluated presented Pro, Ala, Leu, and Ile, which can be part of the peptide fractions with ACE-I_I; with these results obtained these peptides could be used as functional foods related to the control and prevention of diseases related to AHT.

Carriers of Heterozygous Loss-of-Function ACE Mutations Are at Risk for Alzheimer's Disease.

We hypothesized that subjects with heterozygous loss-of-function (LoF) ACE mutations are at risk for Alzheimer's disease because amyloid Aβ42, a primary component of the protein aggregates that accumulate in the brains of AD patients, is cleaved by ACE (angiotensin I-converting enzyme). Thus, decreased ACE activity in the brain, either due to genetic mutation or the effects of ACE inhibitors, could be a risk factor for AD. To explore this hypothesis in the current study, existing SNP databases were analyzed for LoF ACE mutations using four predicting tools, including PolyPhen-2, and compared with the topology of known ACE mutations already associated with AD. The combined frequency of >400 of these LoF-damaging ACE mutations in the general population is quite significant-up to 5%-comparable to the frequency of AD in the population > 70 y.o., which indicates that the contribution of low ACE in the development of AD could be under appreciated. Our analysis suggests several mechanisms by which ACE mutations may be associated with Alzheimer's disease. Systematic analysis of blood ACE levels in patients with all ACE mutations is likely to have clinical significance because available sequencing data will help detect persons with increased risk of late-onset Alzheimer's disease. Patients with transport-deficient ACE mutations (about 20% of damaging ACE mutations) may benefit from preventive or therapeutic treatment with a combination of chemical and pharmacological (e.g., centrally acting ACE inhibitors) chaperones and proteosome inhibitors to restore impaired surface ACE expression, as was shown previously by our group for another transport-deficient ACE mutation-Q1069R.

ACE inhibitory peptides from enzymatic hydrolysate of fermented black sesame seed: Random forest-based optimization, screening, and molecular docking analysis

In this study, black sesame seeds were fermented by Lactobacillus Plantarum NCU116 and then hydrolyzed using acid protease to improve Angiotensin-I-converting enzyme (ACE) inhibitory activity. The random forest-particle swarm optimization (RF-PSO) model was applied to predict the ACE inhibitory activity during the hydrolysis process based on the experimental data. After separating by adsorption chromatography, gel filtration chromatography, and reversed phased-high performance liquid chromatography and then screening in silico method, eight peptides were identified from fermented black sesame seed hydrolysates as ITAPHW, SLPNYHPSPR, QYLPR, IRPNGL, YHNAPIL, LSYPR, GFAGDDAPRA, and LDPNPRSF with IC50 values of 51.69 μM, 146.67 μM, 655.02 μM, 752.60 μM, 1.02 mM, 2.01 mM, 1.97 mM, and 3.43 mM, respectively. ITAPHW and SLPNYHPSPR exhibited high antioxidant activity and inhibited the ACE activity in a non-competitive pattern. Molecular docking revealed that the strong ACE inhibition of ITAPHW and SLPNYHPSPR is probably attributed to the interaction with Zn2+ of ACE.

Identification and In Silico Analysis of ACE-Inhibitory Peptides Derived from Milk Fermented by Lacticaseibacillus paracasei.

Inhibition of angiotensin I-converting enzyme (ACE) activity is an effective way to treat hypertension. In the present study, the ability to produce ACE-inhibitory peptides during fermentation of skimmed milk by the Lacticaseibacillus paracasei M3 strain was evaluated, and the inhibitory mechanism and stability were studied by bioinformatics analysis. The results showed that the ACE inhibition activity of fermented milk was 71.94 ± 1.39%. After digestion with gastric juice and pancreatic juice, the ACE inhibitory activities of the fermented milk were 78.40 ± 1.93 and 74.96 ± 1.73%, respectively. After the fermented milk was purified using ultrafiltration and gel chromatography, 11 peptides from milk proteins were identified and sequenced by Nano LC-MS/MS. Molecular docking displayed that peptide PWIQPK had a high affinity, with ACE showing a binding energy of -6.10 kcal/mol. Hydrogen bonds were formed between PWIQPK and Glu384 in the S1 active pocket of ACE and Asp358. In addition, van der Waals forces were observed. In silico proteolysis suggested that PWIQPK could resist the digestion of pepsin and trypsin, indicating that it is relatively stable in the digestive tract. All results indicate that milk fermented by L. paracasei M3 has the potential to be used as a functional food having antihypertensive effects.

A screening strategy for identifying umami peptides with multiple bioactivities from Stropharia rugosoannulata using in silico approaches and SPR sensing

Umami peptides from natural resources have garnered considerable attention for their potential bioactivities and flavor-enhancing characteristics. In this study, we constructed a database comprising 123 peptides from Stropharia rugosoannulata and screened for umami peptides with both angiotensin I-converting enzyme (ACE) and dipeptidyl peptidase-4 (DPP-IV) inhibitory activities using online prediction tools and molecular docking, and further confirmed by SPR sensing, intelligent sensory and activities test. Five peptides with varying chain lengths were synthesized and by evaluations analyses they exhibited strong umami, with thresholds ranging from 0.105 mmol/L to 0.547 mmol/L. According to the targeted SPR molecular interaction analysis, umami peptides and hT1R3 receptor exhibited a “fast-on/fast-off” binding mode with stronger intensity and persistence than MSG. Furthermore, in vitro experiments revealed that five peptides showed potent ACE and DPP-IV inhibitory activities. Notably, the EAF inhibitory activity was the most significant among the peptides. This comprehensive screening strategy provides a rapid approach for identifying high-sensitivity umami peptides with bioactivities.

Inhibitory effects of the anthocyanins from Lycium ruthenicum Murray on angiotensin-I-converting enzyme: in vitro and molecular docking studies.

Lycium ruthenicum Murray (LRM), a perennial shrub plant belonging to the Solanaceae family, is rich in anthocyanins, which have anti-inflammatory, antioxidant, lipid-lowering, intestinal flora regulating, and other pharmacological qualities. This study was primarily aimed to investigate the inhibitory effect of different anthocyanin purities from LRM on angiotensin-I-converting enzyme (ACE) activity in vitro. Moreover, the inhibitory mechanism was further analyzed by molecular docking technology. Two main anthocyanin isomers were identified by ultra-performance liquid chromatography-tandem mass spectrometry and proton/carbon-13 nuclear magnetic resonance, namely petunidin-3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(β-d-glucopyranoside) (trans-Pt3R5G) and petunidin-3-O-[rhamnopyranosyl-(cis-p-coumaroyl)]-5-O-(β-d-glucopyranoside) (cis-Pt3R5G), with a molar ratio of 9:1. Three purification grades of Pt3R5G all showed excellent inhibitory effects on ACE, with the half maximal inhibitory concentration (IC50 ) values being 0.562, 0.421, and 0.106 mg·mL-1 . Increasing the purity may reduce the IC50 within a certain concentration range. An enzymatic kinetic experiment showed that the inhibitory effect of Pt3R5G on ACE was reversible and non-competitive: Pt3R5G and substrate were not in competition for the active sites of ACE. Molecular docking technology further revealed the possible mechanism was that Pt3R5G and ACE amino acid residues were interacting by hydrogen bonds to exert the inhibitory effect. The results indicated that Pt3R5G from LRM was highly effective at inhibiting ACE activity in vitro, with the hydrogen bonds of Pt3R5G and ACE amino acid residues exerting the inhibition. As a potential plant-based ACE inhibitor, Pt3R5G can be used as a functional ingredient for antihypertensive effects. © 2023 Society of Chemical Industry.

Angiotensin I-Converting Enzyme Inhibitory and Antioxidative Activities of the Bioactive Peptides in the Crude Salt-Soluble Protein Hydrolysates of Pili Nut (Canarium ovatum Engl.) cv. Mayon Kernel

The in silico enzyme digestion and peptide function annotation of pili nut (Canarium ovatum Engl.) 11S globulin protein sequence revealed the presence of bioactive peptides with antihypertensive and antioxidative activities. Molecular docking simulations showed that the proline-histidine (PH) ligand can better inhibit angiotensin I-converting enzyme (ACE) activity than captopril. This result was verified through biochemical assays. Pili kernel protein was extracted with 0.5 M NaCl buffer using the modified Osborne fractionation method, which yielded 100 mg of protein per gram of defatted pili kernel determined via Bradford assay. SDS-PAGE suggested that the protein extract had a major legumin-like (11S) globulin structure with an approximately 57 kDa molecular weight. Enzymatic hydrolysis using pepsin, thermolysin, α-chymotrypsin, and trypsin was used to release the potential antihypertensive and antioxidative peptides with an average rate of 0.03869 mm2 h-1, estimated from band intensity. The hydrolysates were tested for ACE inhibition and free radical scavenging. Captopril and enalapril had %ACE inhibitions of 74.02 and 83.57 %, respectively, whereas the 6 h hydrolysates had a peak %ACE inhibition of 99.73%. These same hydrolysates however, only had 51.32% 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity compared to ascorbic acid, which had 75.59%. These results showed the potential of pili nut as a functional food, especially for preventing high blood pressure and other cardiovascular diseases.

Anchovy’s protein as a potential precursor of Angiotensin-I Converting Enzyme (ACE) inhibitory peptide and Dipeptidyl Peptidase-IV (DPP-IV) inhibitory peptide by an in silico approach

Protein from fish is known as the precursor of biologically active peptides that exert various health benefits such as antihypertensive, antitumor, and immunomodulatory properties. Hence, this study aimed to perform an extraction of anchovy, LC-MS/MS analysis and in silico evaluation of the major proteins in anchovies as potential precursors of biologically active peptides in addition to determining whether such peptides can be released by selected proteolytic enzymes. Anchovy was subjected to protein extraction followed by total soluble protein concentration determination using Bradford assay. The sample was subjected to in-solution trypsin digestion, which was then analysed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). A bioinformatic approach by PEAKS Studio was used to identify the protein. A total of four anchovy’s proteins which are myosin light chain 1, V(D)J recombination-activating protein, 60 kDa chaperonin and heat shock protein 90AA1 were identified. Then, the identified proteins were subjected to in silico approach using the BIOPEP database. The biological potential of the theoretically released angiotensin-I converting enzyme (ACE) inhibitory peptides and dipeptidyl peptidase (DPP)-IV inhibitory peptides were predicted by determining the frequency of occurrence of fragments with a given activity. 60 kDa chaperonin and heat shock protein 90AA1 predicted the highest number of biological activities for ACE inhibitory peptides (284 and 264 fragments) and DPP-IV inhibitory peptides (395 and 409 fragments). The most promising enzyme for the generation of bioactive peptides from anchovy protein was anticipated to be pepsin (pH > 2), which theoretically released a high number of DPP-IV inhibitory peptides and ACE inhibitory peptides through the action of in silico proteolysis. Overall, this work highlighted that anchovy protein could be a promising precursor of bioactive peptides that have ACE and DPP-IV inhibitory activities for developing functional food or nutraceutical products.

Dual antidiabetic and antihypertensive activity of fucoxanthin isolated from Sargassum wightii Greville in in vivo rat model

In a previous study from our laboratory, fucoxanthin purified from brown algae, Sargassum wightii Greville has found to exhibit antioxidant activity and inhibition of angiotensin-I-converting enzyme (ACE) in vitro. The present study aims in understanding the protective effect of fucoxanthin purified from S. wightii against diabetes with hypertension in in vivo. Diabetes and hypertension were induced in rat by streptozotocin and sodium chloride treatment, respectively. In diabetes with hypertension rat, the blood pressure was increased along with hyperglycemia. Administration of fucoxanthin significantly reduced the blood pressure and ACE activity in diabetes with hypertension rat. Furthermore, administration of fucoxanthin significantly reduced the hyperglycemic state. The activity of various enzymes in the liver (hexokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase and fructose-1,6-phosphatase) and serum (creatine kinase) were normalized to that of control level. The level of glycogen, glycoprotein component and lipid profile were equivalent to control level by fucoxanthin administration in diabetes with hypertension rats. Fucoxanthin ameliorated the oxidative stress by preserving the endogenous antioxidant levels in diabetes with hypertension rats. Also, the pancreatic histological integrity was similar to that of control level in diabetes with hypertension rats by fucoxanthin treatment. Altogether, fucoxanthin showed dual antidiabetic and antihypertensive activity in vivo.

Development of lentil peptides with potent antioxidant, antihypertensive, and antidiabetic activities along with umami taste.

Lentil peptides have shown promising bioactive properties regarding the antioxidant activity and also inhibitory activity of angiotensin-I-converting enzyme (ACE). Sequential hydrolysis of proteins has shown a higher degree of hydrolysis with enhanced antioxidant and ACE-inhibitory activities. The lentil protein concentrate (LPC) was sequentially hydrolyzed using Alcalase and Flavourzyme at 2% w/w. The hydrolysate (LPH) was cross-linked (LPHC) or sonicated (LPHUS) and sequentially cross-linked (LPHUSC). Amino acid profile, molecular weight (MW) distribution, DPPH and ABTS radical scavenging activities (RSA; 7mg/mL), ACE (0.1-2mg/mL), α-glucosidase, and α-amylase inhibitory activities (10-500 μg/mL), and umami taste were determined. The highest DPPH RSA was obtained for LPH (68.75%), followed by LPHUSC (67.60%), and LPHUS (67.49%) while the highest ABTS RSA values were obtained for LPHC (97.28%) and LPHUSC (97.20%). Cross-linking and sonication led to the improvement of the ACE-inhibitory activity so that LPHUSC and LPHC had IC50 values of 0.23 and 0.27 mg/mL, respectively. LPHC and LPHUSC also indicated higher α-glucosidase inhibitory activity (IC50 of1.2 and 1.23 mg/mL) compared to LPH (IC50 of1.74 mg/mL) and LPHUS (IC50 of1.75 mg/mL) whilethe IC50 value of acarbose indicated 0.51 mg/mL. Moreover, LPHC and LPHUSC exhibited higher α-amylase inhibitory activities (IC50 of 1.35 and 1.16 mg/mL) than LPHUS (IC50 of 1.95 mg/mL), and LPH (IC50 of 2.51 mg/mL) while acarbose had an IC50 value of 0.43 mg/mL. Umami taste analysis revealed that LPH and LPHC due to MW of 1.7 and 2.3kDa and also high umami amino acids could be well considered as representative of meaty and umami analog flavors while indicating stronger antioxidant, antihypertension, and antidiabetic attributes.

Renal angiotensin I-converting enzyme-deficient mice are protected against aristolochic acid nephropathy

The renal renin-angiotensin system (RAS) is involved in the development of chronic kidney disease. Here, we investigated whether mice with reduced renal angiotensin I-converting enzyme (ACE−/−) are protected against aristolochic acid nephropathy (AAN). To further elucidate potential molecular mechanisms, we assessed the renal abundances of several major RAS components. AAN was induced using aristolochic acid I (AAI). Glomerular filtration rate (GFR) was determined using inulin clearance and renal protein abundances of renin, angiotensinogen, angiotensin I-converting enzyme (ACE) 2, and Mas receptor (Mas) were determined in ACE−/− and C57BL/6J control mice by Western blot analyses. Renal ACE activity was determined using a colorimetric assay and renal angiotensin (Ang) (1–7) concentration was determined by ELISA. GFR was similar in vehicle-treated mice of both strains. AAI decreased GFR in controls but not in ACE−/− mice. Furthermore, AAI decreased renal ACE activity in controls but not in ACE−/− mice. Vehicle-treated ACE−/− mice had significantly higher renal ACE2 and Mas protein abundances than controls. AAI decreased renal ACE2 protein abundance in both strains. Furthermore, AAI increased renal Mas protein abundance, although the latter effect did not reach statistical significance in the ACE−/− mice. Renal Ang(1–7) concentration was similar in vehicle-treated mice of both strains. AAI increased renal Ang(1–7) concentration in the ACE−/− mice but not in the controls. Mice with reduced renal ACE are protected against AAN. Our data suggest that in the face of renal ACE deficiency, AAI may activate the ACE2/Ang(1–7)/Mas axis, which in turn may deploy its reno-protective effects.

Dual Bioactivity of Angiotensin Converting Enzyme Inhibition and Antioxidant Novel Tripeptides from Sipunculus nudus L. and Their Related Mechanism Analysis for Antihypertention

The pathogenesis of hypertension is related to many factors including active angiotensin-I-converting enzyme (ACE) and excess reactive oxygen species (ROS), the combination of ACE inhibition and antioxidant activity in one compound might be useful for the treatment of hypertension. Sipunculus nudus L contain high protein content, which can be used as a valuable raw material to prepare bio-active peptides. In this study, two novel tripeptides, LPK and PRP, with dual bioactivity of ACE inhibition and antioxidant were purified and identified from the worm. The antioxidant activities of LPK and PRP are dose-dependent, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion and hydroxyl radical scavenging activities. Moreover, the antioxidant activity of PRP was stronger than that of LPK. In addition, LPK and PRP also show higher ACE inhibitory activity, with IC50 of 6.54 and 0.42 mM, respectively. Molecular docking simulation showed that both the peptides could interact with the active ACE sites via hydrogen bonds, which can reduce the production of Ang II, thereby; LPK and PRP treatment could decrease Ang II-triggered superoxide production, and meanwhile, the peptides treatment could directly remove excess reactive oxygen species. The above-mentioned advantageous effects appeared to involve the stress of the RAS and scavenging ROS, both were benefit to treat hypertension. This research showed that LPK and PRP had potential to be developed as antihypertension agents, which might be a new strategy for high value utilization of Sipunculus nudus L as functional food material.

Effects of dietary inclusion of Bambara groundnut and sweet orange peels on streptozotocin/HFD type-2 induced diabetes mellitus complications and related biochemical parameters.

The effects of dietary inclusion of Bambara groundnut and sweet orange peels composite bread on low-dose streptozotocin and high-fat diet (HFD)-induced type-2 diabetes mellitus (T2D) complications was evaluated in the present study. Male experimental rats-induced T2D were administered with acarbose (standard) and fed with Bambara groundnut and sweet orange peels composite bread for a period of 14 days while monitoring their blood glucose levels. More so, the activities of angiotensin-I-converting enzyme (ACE), serum aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase activities, as well as nitric oxide (NO), reactive oxygen species (ROS), albumin, total bilirubin, creatinine, urea, and uric acid serum concentrations were assayed for. Diabetic untreated rats showed disorders in ACE, AST, ALT, and ALP activities, and NO, ROS, glucose, albumin, bilirubin, creatinine, urea, uric acid levels, as well as lipid profiles. Interestingly, these disorders were significantly ameliorated in composite bread diet-fed rats in comparison to the diabetic untreated rats. Meanwhile, the presence of polyphenols in the Bambara groundnut and sweet orange peels composite bread diet could have aided the amelioration of these metabolic disorders after the 14th day of administration. Finally, it was proposed that the ability of Bambara groundnut-wheat and sweet orange peel composite bread to treat T2D and its complications makes it a more successful therapy than medications that just target one of the diseased states. PRACTICAL APPLICATIONS: Diabetes mellitus is a global and chronic disease that presently affects 536.6 million people alongside 1.5 million deaths directly attributed to it yearly. Several drug and medicinal agents have been employed for the management of diabetes but those drugs are mostly limited to the management of diabetes while the associated complications are most untreated, while drugs that can manage diabetes and its related complications mostly come at high prices. Therefore, there is an urgent need to evaluate legumes, such as Bambara groundnut, with proven therapeutic potential in the management of diabetes and its complications. However, the Bambara groundnut takes a long period to prepare for a meal, therefore including it in a ready-to-eat product will not only improve its acceptability but also add to economic improvement. Furthermore, adding a waste product, sweet orange peels, will both add flavor and source of additional antioxidant attributes.

Angiotensin I converting enzyme (ACE) inhibitory activity and antihypertensive effects of rice peptides

In this paper, the antihypertension effect of rice peptide (RP) was studied. With spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) as the research objects, RP disposable gastric and long-term gastric irrigation experiments were carried out and systolic blood pressure (SBP) was measured. At the end of the long-term gastric irrigation experiment, the content of nitric oxide (NO), angiotensin-converting enzyme (ACE), angiotensin II (Ang II) and renin in the plasma and the activity of ACE were determined. The results showed that RP could reduce systolic pressure of SHR and had time-dose dependence while high-dose RP significantly reduced systolic pressure by 24.6 and 17.2 mmHg, respectively after a single and long-term gastric irrigation test. RP also could inhibit the activity of ACE and increase the release of NO. These results suggested that the decompression mechanism of RP is likely to be related to the regulation of the renin-angiotensin system (RAS) and NO.

Effects of Inherent Lactic Acid Bacteria on Inhibition of Angiotensin I-Converting Enzyme and Antioxidant Activities in Dry-Cured Meat Products.

The aim of this study was to investigate the inherent bacteria that contribute to expressing the angiotensin I-converting enzyme (ACE) inhibitory activity and the antioxidant activity of dry-cured meat products without a bacterial starter. Among the ten dry-cured meat product samples, Coppa and Milano salami exhibited high ACE inhibitory activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, and oxygen radical absorbance capacity (ORAC). No consistent trend was observed in the pH values or the total peptide and imidazole dipeptide concentration of the products that exhibited high ACE inhibitory and antioxidant activities in the tested samples. To investigate the bacteria contributing to the ACE inhibitory and antioxidant activities of the product, 16S rRNA sequencing analysis, isolation, and identification of bacteria were performed using not only Coppa and Milano salami but also the Jamon Serrano and Parma prosciutto products that had low functional activities. Results suggest the Lactobacillales order, particularly the species Latilactobacillus sakei and Pediococcus pentosaceus, were the main inherent bacteria in Coppa and Milano salami, respectively, compared with the Jamon Serrano and Parma prosciutto products. Therefore, the inherent lactic acid bacteria in dry-cured meat products without bacterial starter is important for ACE inhibitory and antioxidant activities of the products.

Codonopsis pilosula and fish collagen yogurt: Proteolytic, potential Angiotensin-I converting enzyme (ACE) inhibitory activity and sensory properties

The effects of Codonopsis pilosula (CP) and/or fish collagen (FC) on post-acidification, proteolysis of milk proteins, angiotensin-I converting enzyme (ACE) inhibitory activity, and sensory evaluation were investigated in yogurt during 0, 7, & 21 days of storage at 4 °C. Two groups of yogurt samples were prepared: group 1 included plain yogurt (control) and CP-yogurt; group 2 included plain yogurt + FC (control) and CP-yogurt + FC. CP- yogurt showed a significant increase in total titratable acidity (TTA) on day 7 of storage. The presence of FC in yogurt significantly improved (p < 0.05) the content of free amino acids (FAA) compared to the absence. O-phthaldialdehyde (OPA) peptide concentration increased (p < 0.05) to the highest amount for CP-yogurt ± FC on day 7 of storage. In addition, more degradation was observed in bovine serum albumin (BSA), α-, β-, & κ-caseins, β-lactoglobulin, and α-lactalbumin of CP- yogurt + FC than its control on day 7 of storage. CP- yogurt with/without FC showed higher (p < 0.05) inhibitory ACE activity than their respective controls on day 7 of storage. The addition of fish collagen in CP- yogurt seemed to have good scoring in sensory evaluation. In conclusion, the presence of C. pilosula and fish collagen in the yogurt can bring about promising health benefits such as anti-ACE activity.

P607. Effect of Antipsychotics in the Angiotensin Converting Enzyme-1 (ACE) Activity in First-Episode Psychosis Patients and Animal Models for Schizophrenia

Angiotensin-I converting enzyme (ACE) is a key component of renin-angiotensin system (RAS), and its association with cognitive impairments in brain disorders has been recently recognized. Higher ACE activity in plasma of chronic patients with schizophrenia (SCZ) compared with healthy controls (HCs) paired by sex and age, and the relevance of ACE activity in SCZ was suggested by us. We now propose a translational analysis to understand how SCZ pharmacotherapy with antipsychotics can affect the ACE activity in clinical samples and animal model for SCZ studies.

Novel ACE inhibitory peptides derived from whey protein hydrolysates: Identification and molecular docking analysis

Angiotensin I-converting enzyme (ACE) plays a significant role in the regulation of blood pressure via generating angiotensin II (Ang II). Using natural inhibitors to block the activity of ACE is an alternative method to minimize the side effects of commercial drugs, and is a major goal of hypertension management. This study detected the presence of ACE inhibitory peptides in whey protein hydrolysate. The whey protein hydrolysate was separated sequentially by ultrafiltration and RP-HPLC. LC-MS/MS revealed the amino acid sequences of the fractions and four potential ACE inhibitory peptides were selected (PQVSTPTL, MPGP, PMHIR, PPLT) for synthesis. IC50 values of these four peptides were 86 ± 8, 179 ± 4, 90 ± 6, and 168 ± 4 μM, respectively. Then, molecular docking analysis was used to assess how these peptides interact with ACE. PQVSTPTL exhibited the lowest binding energy (−6.64 kcal/mol) with the ACE molecule. These four reported peptides were with no allergenicity nor toxicity. These results indicated that whey protein hydrolysate could be a suitable resource for obtaining novel inhibitory peptides against ACE and provides information for obtaining novel ACE inhibitors for hypertension management.

Alchemilla viridiflora Rothm.: the potent natural inhibitor of angiotensin I-converting enzyme.

Alchemilla viridiflora Rothm., Rosaceae is a herbaceous plant widespread in central Greece, Bulgaria, North Macedonia and Serbia with Kosovo. Liquid chromatography-mass spectrometry analysis leads to the identification of 20 compounds in methanol extract, mainly ellagitannins and flavonoid glycosides. Given that various plant extracts have traditionally been used to treat hypertension and that some of the analyzed methanol extract constituents have beneficial cardiovascular effects, we hypothesized that some of these effects are achieved by inhibiting angiotensin I-converting enzyme (ACE). The dose-dependent ACE inhibitory activities of A. viridiflora and miquelianin were observed with an IC50 of 2.51 ± 0.00µg/mL of A. viridiflora extract compared to the IC50 of 5.4139 ± 0.00µM for miquelianin. The contribution of the single compounds to the tested activity was further analyzed through the in silico experimental approach. Computational docking results showed that tiliroside, ellagic acid pentose and galloyl-hexahydroxydiphenoyl-glucose exhibited even better binding affinity for the ACE active site than miquelianin, for which ACE activity was confirmed by an in vitro assay.

Recent findings on the cellular and molecular mechanisms of action of novel food-derived antihypertensive peptides

Hypertension impacts negatively on the quality of life of sufferers, and complications associated with uncontrolled hypertension are life-threatening. Hence, many research efforts are exploring the antihypertensive properties of bioactive peptides derived from food proteins using in vitro ACE-inhibitory assay, experimentally-induced and spontaneous hypertensive rats, normotensive and hypertensive human models. In this study, the cellular and molecular mechanisms of blood pressure-lowering properties of novel peptides reported in recent studies (2015-July 30, 2021) were discussed. In addition to common mechanisms such as the inhibition of angiotensin I-converting enzyme (ACE) and renin activities, recently recognized mechanisms through which bioactive peptides exert their antihypertensive properties including the induction of vasodilation via upregulation of cyclo-oxygenase (COX) and prostaglandin receptor and endothelial nitric oxide synthase expression and L-type Ca2+ channel blockade were presented. Similarly, emerging mechanisms of blood pressure-lowering by bioactive peptides such as modulation of inflammation (TNF-α, and other cytokines signaling), oxidative stress (Keap-1/Nrf2/ARE/HO-1 and related signaling pathways), PPAR-γ/caspase3/MAPK signaling pathways and inhibition of lipid accumulation were discussed. The review also highlighted factors that influence the antihypertensive properties of peptides such as method of hydrolysis (type and number of enzymes, and chemical used for hydrolysis, and microbial fermentation), and amino acid sequence and chain length of peptides.