ACE-inhibitory Activity Research Articles

Angiotensin-Converting Enzyme (ACE)-Inhibitor Activity of Novel Peptides Derived from Porcine Liver and Placenta

Peptides isolated from various biological materials are potential sources for novel angiotensin-converting enzyme (ACE) inhibitors. Here, the ACE-inhibitory activity of peptides derived from papain-digested hydrolysates of porcine liver and placenta were investigated. A high-throughput method was developed to identify potential bioactive peptides from the hydrolysates using in silico enzymatic cleavage, HPLC-MS/MS, and bioinformatics tools. Four peptides (FWG, MFLG, SDPPLVFVG, and FFNDA) were selected based on their predicted bioactivity, then synthesised and tested for ACE inhibition. All samples demonstrated ACE-inhibitory activity, with FWG and MFLG showing greater potency than SDPPLVFVG and FFNDA. The placenta hydrolysate outperformed both the liver hydrolysate and synthetic peptides in ACE inhibition, possibly due to it containing a higher proportion of dipeptides. The synthetic peptides’ IC50 values were comparable to those reported for porcine muscle-derived peptides in previous studies. While less potent than the commercial ACE inhibitor captopril, the identified peptides showed promising ACE-inhibitory activity. This research demonstrates the potential of porcine liver and placenta as sources of novel ACE-inhibitory peptides and highlights the effectiveness of the developed high-throughput method for identifying bioactive peptides; this method could subsequently be adapted to other peptide sources, facilitating the development of innovative functional foods or nutraceuticals.

Hempseed Water-Soluble Protein Fraction and Its Hydrolysate Display Different Biological Features

Hempseeds, from the Cannabis sativa plant, and its derivates are a versatile food option for various dietary preferences. Due to their aminoacidic profile, researchers have studied the presence of bioactive peptides in hempseed proteins. In this study, the water-soluble fraction of hempseed protein was extracted, and the derived peptides were analyzed. The investigation focused on their biological function, particularly their antioxidant activity. Several biological functions have arisen, such as angiotensin-converting enzyme inhibition activity, dipeptidyl-peptidase IV, dipeptidyl-peptidase III inhibition, and ubiquitin-mediated proteolysis activation. The hydrolysates show greater 2,2-azinobis-[3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging activity compared to the proteins (97.95 ± 4.48 versus 81.04 ± 10.63). Furthermore, the impact of these proteins and peptides on the U937 cell line was evaluated to assess cell viability and their potential role in modulating inflammation associated with gastrointestinal autoimmune diseases. Protein treatment resulted in a significant reduction in cell viability, as opposed to hydrolysates, which did not affect it.

Preparation of Novel ACE Inhibitory Peptides from Skimmed Goat Milk Hydrolyzed by Multi-Enzymes: Process Optimization, Purification, and Identification

This study optimizes the process conditions for preparing angiotensin-converting enzyme (ACE) inhibitory peptides from skimmed goat milk (SGM) hydrolyzed by multi-enzymes using response surface methodology. When the enzymatic hydrolysis time was 90 min, the optimal hydrolysis conditions were a pH of 8.49, enzyme-to-substrate ratio (E/S ratio) of 8.04%, and temperature of 61.54 °C. The hydrolysis degree and ACE inhibitory activity were 65.39% ± 0.01% and 84.65% ± 0.03%, respectively. After purification by ultrafiltration, macroporous resin, and gel filtration, the ACE inhibitory activity of F2-2 in the two components of F2 was higher, with the ACE inhibitory rate of 93.97% ± 0.15% and IC50 of 0.121 ± 0.004 mg/mL. The content of hydrophobic amino acids, fatty amino acids, and aromatic amino acids in component F2-2 accounts for 73.17%, 33.86%, and 33.72%, respectively. Eleven peptides were isolated and identified from the F2-2 components of the enzymatic hydrolysate of SGM, including two peptides without an established database. The peptides mainly came from β casein, αS1 casein, and αS2 casein.

Identification and characterization of umami-ACE inhibitory peptides from traditional fermented soybean curds.

Fermented soybean curds (FSC) are popular because of its umami taste. Its bioactivities are of interest. Peptides in FSC were identified using nano-HPLC-MS/MS, and 11 candidate peptides showing potential umami and ACE inhibitory activities were screened using various databases. Pharmacophore model analysis showed their high probability of ACE inhibition with fit values >2, which showed the peptides bound to umami receptors and ACE mainly through hydrogen bond, and electrostatic and hydrophobic interactions. Additionally, their docking and interaction energy were independent of the peptide length. Three high umami-ACE inhibitory peptides (VE, FEF, and WEEF) were synthesized. Their umami thresholds were WEEF (0.32mM)<FEF (0.55mM)<VE (1.10mM), while their IC50 were WEEF (85±2μM)<FEF (170±10μM)<VE (205±5μM). NO and ET-1 production were dose-dependent with WEEF showing the best ACE inhibitory activity. The results allowed identification of effective umami agents and ACE inhibitory peptides from fermented soybean products. It could also be useful method for screening potential umami-ACE inhibitory peptides.

Changes in functional activities and volatile flavor compounds of fermented mung beans, cowpeas, and quinoa started with Bacillus amyloliquefaciens SY07.

In this work, the functional activities including α-glucosidase, α-amylase, angiotensin converting enzyme (ACE) inhibitory activity, and antioxidant activity of mixed grains (mung beans, cowpeas, and quinoa) fermented with Bacillus amyloliquefaciens SY07 were investigated. The volatile flavor of the mixed grains collected every 12h during 72h-fermentation were further detected as well. The inhibition on α-glucosidase and α-amylase reached up to 89.34% and 50.03% with the sample concentration of 5.17 and 9.38mg/mL, respectively. Moreover, the ACE inhibitory activity reached to 93.66% with the sample concentration of 0.59mg/mL. The antioxidant capacity of the mixed grains, evaluated by ABTS and DPPH radical scavenging capacities and ferric ion reducing power, was also significantly improved (p<0.05) during fermentation. The maximum of ABTS and DPPH radical scavenging capacities increased to 8.64 and 3.21mg TE/g DW, respectively, and the maximum ferric ion reducing power reached to 5.73mg TE/g DW. Twenty-one volatile flavor compounds with odor activity values (OAVs)≥1 were detected, and six key volatile flavor substances were identified by OPLS-DA analysis, namely, isovaleric acid, acetoin, phenylacetic acid, (Z)-2-nonenol, 1-hexanol, and 1-octen-3-ol, with overall strong creamy, sweet, baked-potato, and cocoa flavors upon fermentation. These findings revealed a favorable pathway for B. amyloliquefaciens SY07 to be used to improve the functional and flavor properties of fermented grains, which would also be of great value for further elucidating the mechanism of the formation of the volatile flavor differences and developing novel quality cereal-based products.

In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction

Many natural angiotensin-converting enzyme inhibitory (ACEI) peptides have been widely studied. However, their stability in vivo is poor in most cases. In this study, peptides were initially digested from broccoli in vitro, and absorption was simulated by Caco2 cells transport and then analyzed by Peptideomics and molecular docking. Subsequently, the mechanisms were verified using a high glucose-induced vascular smooth muscle cells (VSMCs) dysfunction model. Results showed that ACEI activity of broccoli crude peptide increased by 70.73 ± 1.42% after digestion. The enzymatic hydrolysates of crude broccoli peptides before and after digestion were detected by HPLC. The digested crude peptides were highly stable (with a stability level &amp;gt; 90%) in the intestine and possessed a strong absorptive potential. Five peptides with high stability and strong permeability were first identified, including HLEVR, LTEVR, LEHGF, HLVNK, and LLDGR, which exhibited high activity with IC50 values of 3.19 ± 0.23 mM, 17.07 ± 1.37 mM, 0.64 ± 0.02 mM, 0.06 ± 0.01 mM, and 2.81 ± 0.12 mM, respectively. When the VSMCs model was exposed to Ang II, the expressions of PCNA, MMP2, and Bcl2 were increased, while the expression of BAX was inhibited. When the VSMCs was exposed to high glucose (HG), the Ang II concentration significantly increased. This indicates that HG elevated Ang II levels. Finally, five peptides significantly attenuated Ang II-induced VSMCs proliferation and migration by down-regulating AT1R expression and inhibiting ERK and p38 MAPK phosphorylation. Notably, in exploring VSMCs dysfunction on a high glucose-induced model, ACEI peptides resulted in down-regulation of ACE and up-regulation of ACE2 expression. Therefore, it can be further referenced for the functional food against hypertension and cardiovascular diseases.

Pyridine Derivatives and Furan Derivatives Identified from the Medicinal Mushroom Irpex lacteus SY1002.

Three new pyridine derivatives, irpelactedines A-C (1-3), and a new furan derivative, irpelactedine D (5), along with two structurally related known compounds, irpexidine A (4) and 5-carboxy-2-furanpropanoic acid (6), were isolated from the medicinal fungus Irpex lacteus SY1002. Their structures were elucidated through NMR and mass spectral analyses, combined with density functional theory calculations of ECD data. Evaluation of angiotensin-converting enzyme (ACE) inhibitory activity revealed that compounds 1 and 3 displayed moderate inhibition, with IC50 values of 31.49 ± 3.41 and 80.96 ± 6.93 µg/mL, respectively. Molecular docking suggested that compound 1 bound to the active site of ACE, leading to a reduction in its activity. Furthermore, cytotoxicity and antimicrobial activity tests revealed the low toxicity of these compounds. This is the first report on the ACE inhibitory activity of this class of pyridine derivatives, providing valuable insights into exploring the medicinal potential of I. lacteus and offering a structural template for developing new ACE inhibitors. Future efforts will focus on optimizing their structure and conducting in vivo testing to assess their therapeutic potential.

Identification of barley-derived peptides with angiotensin converting enzyme inhibitory activity

Identification of barley-derived peptides with angiotensin converting enzyme inhibitory activity

Determination of synbiotic mango fruit yogurt and its bioactive peptides for biofunctional properties.

Yogurt is one of the most popular fermented milk products consumed worldwide. Fortification of yogurt with different food components, including fruit pulp, is a common practice to make it more palatable and healthier. In India, mango fruit is easily available. It is rich in nutrients and bioactive components. However, in-depth studies on mango fruit yogurt are scarce. Therefore, in this study, we prepared synbiotic mango fruit yogurt using response surface methodology (RSM) with three different independent factors (sugar 4%-6%; prebiotic inulin 1%-3%, and mango pulp 5%-15%) to determine the response antioxidant activity. The optimal conditions were as follows: sugar 6%, mango fruit pulp 6.562%, and prebiotic inulin 1%. There were no significant differences between the results of the experimental and predicted values of antioxidant activity by this model. The optimized product was analyzed for physicochemical, biofunctional, and technofunctional properties, including total polyphenol content, total flavonoid content, proteolytic activity, antioxidant activity, and ACE-inhibitory activity. The bioactive peptides derived from synbiotic mango fruit yogurt were also extracted (3kDa, 5kDa and 10kDa) and determined for their biofunctional attributes. The antioxidant activity was recorded as 1,047.95 ± 2.20mmol/L, 1,208.07 ± 2.92mmol/L, and 1,293.09 ± 1.10mmol/L Trolox equivalent antioxidant capacity, while ACE-inhibitory activity was 45.68% ± 1.23%, 64.20% ± 1.24% and 82.72% ± 1.24% inhibition in 3kDa, 5kDa, and 10kDa, respectively. The 10kDa bioactive peptide exhibited superior results than the 3kDa and 5kDa peptides. The synbiotic mango fruit yogurt and its bioactive peptides showed significant biofunctional activities.

Study on Fermentation Preparation, Stability, and Angiotensin-Converting Enzyme Inhibitory Activity of Tomato Pomace Peptide.

The substantial quantity of discarded tomato pomace (TP) results in the waste of valuable resources. This study utilizes these tomato by-products by mixing them with water in a specific proportion and fermenting the mixture in two stages: first with yeast, and then with lactic acid bacteria. The most suitable microbial strains for TP fermentation were identified by evaluating parameters such as peptide content, degree of hydrolysis, and gel electrophoresis analysis. Subsequently, tomato pomace peptides (TPPs) were separated into peptides of different molecular weights using ultrafiltration. The IC50 values, ACE inhibitory activities, and in vitro stability of these peptides were compared, and their secondary structures and microstructures were characterized. The results indicated that the soluble protein concentration increased from 26.25 mg/g to 39.03 mg/g after 32 h of fermentation with strain RV171. After an additional 32 h of fermentation with Bifidobacterium thermophilum, the peptide content reached 49.18 ± 0.43%. SDS-PAGE gel electrophoresis showed that the TPP molecular weights were predominantly below 10 kDa. The IC50 results demonstrated that fractions with smaller molecular weights exhibited greater ACE inhibitory activities. Structural analysis confirmed that the TP hydrolysate was indeed a peptide.

Identification of a Synthetic Peptide with Potential Angiotensin I-Converting Enzyme (ACE-1) Inhibitory Activity

Identification of a Synthetic Peptide with Potential Angiotensin I-Converting Enzyme (ACE-1) Inhibitory Activity

In Silico, Molecular Docking and In Vitro angiotensin-converting enzyme-inhibitory activity of PGYALQR peptide derived from fish waste hydrolysate

In recent decades, Angiotensin-converting enzyme (ACE) inhibitory peptides derived from various proteins have become crucial sources of health-enhancing components for clinical use. Abundant proteins in fish waste entrails can be used to produce ACE inhibitory peptides. Catfish, Tilapia, and Mackerel entrails were digested by pepsin and passed through the 3kDa cutoff column. The protein hydrolysate passed through the 3kDa cutoff column and C18 column were analyzed for an ACE inhibitory activities and sequenced using LC-MS/MS. Five candidate peptides from De novo sequencing was chemically synthesized and tested for ACE inhibitory activity. The ACE inhibitory activity result revealed that PGYALQR peptide contains ACE inhibitory activity as captopril did. This study aims to predict the conformation and orientation of the PGYALQR peptide into the binding site of ACE. Molecular docking analysis using AutoDock Vina was performed to elucidate the mechanisms underlying the ACE-inhibitory activity of the PGYALQR peptide. Computational analysis revealed that the peptide binds to the ACE active site with −11.2 kcal/mol, forming hydrogen bonds with Glu162, Gln281, His353, Ala354, Lys511, His513, and Tyr523. In comparision, captopril interacted with Gln281, His353, Lys511, His513, Tyr520, and Tyr523 with a binding energy of −5.9 kcal/mol. Additionally, the peptide interacts with the Zn (II) ion in the ACE active site, coordinating with the residues Glu411, His383, and His387, which is crucial for enhancing its inhibitory activity of ACE. It may contort the tetrahedral coordination of the Zn (II), resulting in loss of ACE activity.

Unearthing novel and multifunctional peptides in peptidome of fermented chhurpi cheese of Indian Himalayan region.

Fermented foods of the Indian Himalaya are unexplored functional resources with high nutritional potential. Chhurpi cheese, fermented by defined native proteolytic lactic acid bacteria of Sikkim was assessed for ACE inhibitory, HOCl reducing, and MPO inhibitory, activity across varying stages of gastrointestinal (GI) digestion. The enhanced bioactivity of Lactobacillus delbrueckii WS4 chhurpi was associated with the generation of bioactive and multifunctional peptides during fermentation and GI digestion. Qualitative and quantitative in silico tools were employed for prediction of ACE inhibitory activity of novel chhurpi peptides. Selected peptides, with highest predictive ACE inhibitory potential were synthesized and in vitro validation revealed the ACE inhibitory potential of peptides HPHPHLSFM and LKPTPEGDL. LKPTPEGDL showed the most potent ACE inhibitory activity (IC50 of 25.82±0.26µmol) which slightly decreased upon GI digestion. The peptides demonstrated a non-competitive type mixed ACE inhibition modality. Furthermore, the two peptides exerted observable HOCl reducing and MPO inhibitory activity, demonstrating their antioxidative potential. HPHPHLSFM exhibited superior HOCl reduction (EC50 of 0.29±0.01mmol), while LKPTPEGDL demonstrated higher MPO (IC50of 0.29±0.01mmol) inhibition. Molecular docking of the two peptides with MPO revealed proline and aspartate near peptidyl C-terminus to bind with enzyme catalytic residues. This study presents the first peptidome analysis of chhurpi produced through controlled fermentation and identifies novel peptides with MPO and ACE inhibitory activity. Furthermore, it marks the first synthesis and in vitro bioactivity validation of bioactive peptides from chhurpi cheese, highlighting its multifunctional potential.

ACE-inhibitory activity and antioxidant properties of a low MW rice bran protein hydrolysate

ACE-inhibitory activity and antioxidant properties of a low MW rice bran protein hydrolysate

Comprehensive chemical profile, angiotensin-I converting enzyme inhibitory and calcium chelation activity of rice wine lees and rice vinegar residues: A novel development strategy

Comprehensive chemical profile, angiotensin-I converting enzyme inhibitory and calcium chelation activity of rice wine lees and rice vinegar residues: A novel development strategy

Integrated network pharmacology and experimental validation to explore the mechanisms of Coregonus peled-derived myosin ACE-inhibiting peptides for the treatment of hypertension

Coregonus peled is rich in protein and is a plentiful resource of bioactive peptides. This study was aimed at extracting novel Angiotensin I-converting enzyme (ACE) inhibitory peptides from Coregonus peled and revealing their potential hypotensive mechanisms. This paper screened six ACE inhibitory peptides with high bioactivity, good water solubility, and ADMET properties by computerized enzyme digestion of myosin-heavy chain from Coregonus peled, and LCYPR had the greatest ACE inhibition activity (IC50 = 47.8782 μM). There were 47 potentially critical targets of LCYPR for hypertension treatment, involving 135 biological processes (BP), 30 cellular components (CC), and 30 molecular functions (MF). The results of KEGG pathway analyse showed that the LCYPR participated in 50 pathways including the renin-angiotensin system, renin secretion, lipid and atherosclerosis, relaxin signaling pathway, IL-17 signaling pathway, atherosclerosis, fluid shear stress, and others, through the key targets such as AGT, AKT1, ACE, REN, CTSB, STAT3, PLG, SRC, MMP2, and F2 to regulate the blood pressure of organisms. In conclusion, the study obtained a novel ACE inhibitory peptide from the myosin-heavy chain of Coregonus peled and revealed the potential target and pathway of LCYPR to improve hypertension. The study provides new ideas and methods for developing novel antihypertensive peptides. The results provide a theoretical basis for developing functional foods of the Xinjiang specialty cold-water fish.

Evaluation and validation of angiotensin-converting enzyme inhibitory activity of moringa oleifera, quercetin, and isoquercetin: A comparative study of fluorescence and absorbance measurement methods

Evaluation and validation of angiotensin-converting enzyme inhibitory activity of moringa oleifera, quercetin, and isoquercetin: A comparative study of fluorescence and absorbance measurement methods

Preparation and identification novel angiotensin-converting enzyme-inhibitory peptides derived from fish waste

The purpose of the research is to compare short peptides from different hydrolysates of fish entrails that can inhibit the activity of angiotensin-converting enzyme (ACE). Fish hydrolysates derived from Catfish, Tilapia, and Mackerel entrails were digested by pepsin and passed through the 3kDa cutoff column. The fraction containing peptides shorter than and equal to 3kDa from catfish hydrolysate has the great ability to inhibit ACE activity in converting the substrate (Furanacroloy-Phe-Gly-Gly, FAPGG) and producing FAP and GG as the products of the reaction. The 3kDa filtrate from the catfish hydrolysate had activity like Captopril, a drug for treating hypertension. The 3kDa filtrate derived from the catfish entrail hydrolysate was purified using OFFGEL electrophoresis and then passed through the C18 column. The 3kDa filtrate was separated into two fractions and then these fractions were determined ACE inhibitory activity. The result showed that the fractions containing hydrophilic peptides and others containing hydrophobic peptides possessed inhibitory activity against ACE. Those fractions were analyzed with LCMS/MS for sequencing. The results revealed that synthesized peptides; ASNLHGV, LFKDLR, PGYALQR, and LETAKSR, derived from the catfish hydrolysate showed anti-ACE activity against its substrate.

Changes of low-abundance peptides in frozen orange juice before and after frozen storage and pasteurization processing, and their contribution to ACE inhibition activity

Changes of low-abundance peptides in frozen orange juice before and after frozen storage and pasteurization processing, and their contribution to ACE inhibition activity

Comprehensive Review of Biological Functions and Therapeutic Potential of Perilla Seed Meal Proteins and Peptides

This comprehensive review explores the biological functions of Perilla frutescens seed proteins and peptides, highlighting their significant potential for health and therapeutic applications. This review delves into the mechanisms through which perilla peptides combat oxidative stress and protect cells from oxidative damage, encompassing free radical scavenging, metal chelating, in vivo antioxidant, and cytoprotective activities. Perilla peptides exhibit robust anti-aging properties by activating the Nrf2 pathway, enhancing cellular antioxidant capacity, and supporting skin health through the promotion of keratinocyte growth, maintenance of collagen integrity, and reduction in senescent cells. Additionally, they demonstrate antidiabetic activity by inhibiting α-amylase and α-glucosidase. The cardioprotective effects of perilla peptides are underscored by ACE-inhibitory activities and combat oxidative stress through enhanced antioxidant defenses. Further, perilla peptides contribute to improved gut health by enhancing beneficial gut flora and reinforcing intestinal barriers. In liver, kidney, and testicular health, they reduce oxidative stress and apoptotic damage while normalizing electrolyte levels and protecting against cyclophosphamide-induced reproductive and endocrine disruptions by restoring hormone synthesis. Promising anticancer potential is also demonstrated by perilla peptides through the inhibition of key cancer cell lines, alongside their anti-inflammatory and immunomodulating activities. Their anti-fatigue effects enhance exercise performance and muscle function, while perilla seed peptide nanoparticles show potential for targeted drug delivery. The diverse applications of perilla peptides support their potential as functional food additives and therapeutic agents.