Angiotensin I-converting Enzyme Inhibitor Research Articles

Peptide Inhibitors of Angiotensin-I Converting Enzyme (ACE) Bioavailability in Legumes Subjected to Hydrothermal Treatment

The objective of this study was to evaluate the effect of Angiotensin-I Converting Enzyme (ACE) inhibitory peptides derived from five legumes (Vigna unguiculata, Cicer arietinum, Lens culinaris, Vicia faba, and Phaseolus vulgaris) after undergoing a hydrothermal treatment. The seeds were divided into two groups: one was subjected to drying and grinding, and the other one to cooking for 2 hours (100 °C), followed by drying and grinding. The flours obtained from the different processes were subjected to digestion with pepsin-pancreatin, and the resulting peptides were evaluated for their ACE inhibitory activity. The obtained results were subjected to analysis of variance and Tukey's test. The group consisting of the treatments V. unguiculata (82.63%), V. unguiculata cooked (96.41%), and C. arietinum (80.84%) showed the highest percentages of ACE inhibition, while the group comprising V. faba (6.0%), cooked L. culinaris (3.03%), and P. vulgaris (4.0%) exhibited the lowest inhibition percentages. These results demonstrate that V. unguiculata, V. faba, and C. arietinum can undergo hydrothermal treatment while still retaining their bioactive potential, ensuring a cooked flour, ready for formulating a multifunctional food.

How do in vitro digestion and cell metabolism affect the biological activity and phenolic profile of grape juice and wine

Cabernet Sauvignon grape juice and wine underwent in vitro digestion, resulting in a reduction of most phenolic compounds (10%–100% decline), notably impacting anthocyanins (82%–100% decline) due to pH variations. However, specific phenolics, including p–hydroxybenzoic, protocatechuic, vanillic, p-coumaric, gallic and syringic acids, and coumarin esculetin, increased in concentration (10%–120%). Grape juice and wine samples showed comparable polyphenolic profile during all phases of digestion. Antioxidant activity persisted, and inhibition of angiotensin-I converting enzyme was improved after the digestion process, likely because of increased concentrations of listed phenolic acids and esculetin. Digested grape juice displayed comparable or superior bioactivity to red wine, indicating it as a promising source of accessible grape polyphenols for a broader audience. Nevertheless, Caco-2 cell model metabolization experiments revealed that only 3 of 42 analyzed compounds passed to the basolateral compartment, emphasizing the significant impact of digestion on polyphenol bioactivity, suggesting potential yet unmeasurable and overlooked implications for human health.

A novel angiotensin I-converting enzyme inhibitory peptide from walnut (Juglans sigillata) protein hydrolysates and its evaluation in Ang II-induced HUVECs and hypertensive rats

This study aims to seek angiotensin-I-converting enzyme inhibitory (ACEi) peptides from walnut using different enzymatic hydrolysis, and further to validate the potent ACEi peptides identified and screened via peptidomics and in silico analysis against hypertension in spontaneously hypertensive rats (SHRs). Results showed that walnut protein hydrolysate (WPH) prepared by combination of alcalase and simulated gastrointestinal digestion exhibited high ACEi activity. WPH was separated via Sephadex-G25, and four peptides were identified, screened and verified based on their PeptideRanker score, structural characteristic and ACE inhibition. Interestingly, FDWLR showed the highest ACEi activity with IC50 value of 8.02 μg/mL, which might be related to its close affinity with ACE observed in molecular docking. Subsequently, high absorption and non-toxicity of FDWLR was predicted via in silico absorption, distribution, metabolism, excretion and toxicity. Furthermore, FDWLR exhibited positively vasoregulation in Ang II-induced human umbilical vein endothelial cells, and great blood pressure lowering effect in SHRs.

Evaluation of Thai Silkworm (Bombyx mori L.) Hydrolysate Powder for Blood Pressure Reduction in Hypertensive Rats.

The angiotensin-I converting enzyme (ACE) plays a pivotal role in hypertension, and while ACE inhibitors are conventional in hypertension management, synthetic medications often carry undesirable side effects. This has spurred interest in alternative ACE inhibitors derived from natural sources, such as edible insects. The silkworm, recognized for its bioactive peptides with potent ACE-inhibitory properties, has emerged as a promising candidate. This study aims to evaluate the acute toxicity and assess the antihypertensive efficacy of crude mature silkworm hydrolysate powder (MSHP) obtained from mature Thai silkworms. Utilizing the commercial protease Alcalase®2.4L, MSHP was administered at various doses, including 50, 100, and 200 mg kg-1, to hypertensive rats. The investigation spans a 14-day period to observe any potential acute toxic effects. Results indicate that MSHP exhibits LD50 values equal to or exceeding 2000 mg kg-1, signifying a low level of acute toxicity. Furthermore, the effective dose for blood pressure reduction in hypertensive rats surpasses 100 mg kg-1 of rat body weight. These findings suggest that MSHP derived from Thai mature silkworms holds promise as a natural antihypertensive food source. The implications of this research extend to the development of functional foods, functional ingredients, and dietary supplements aimed at managing hypertension.

The first bioactive (angiotensin-converting enzyme-inhibitory) peptide isolated from pearl matrix protein

In this research, we unveil the medical potential of pearls by identifying a novel bioactive peptide within them for the first time. The peptide, termed KKCHFWPFPW, emerges as a pioneering angiotensin I-converting enzyme (ACE) inhibitor, originating from the pearl matrix of Pinctada fucata. Employing quadrupole time-of-flight mass spectrometry, this peptide was meticulously selected and pinpointed. With a molecular weight of 1417.5 Da and a theoretical isoelectric point of 9.31, its inhibitory potency was demonstrated through a half-maximal inhibitory concentration (IC50) of 4.17 μM, established via high-performance liquid chromatography. The inhibition of ACE by this peptide was found to be competitive, as revealed by Lineweaver–Burk plot analysis, where an increase in peptide concentration correlated with an enhanced rate of ACE inhibition. To delve into the interaction between KKCHFWPFPW and ACE, molecular docking simulations were conducted using the Maestro 2022-1 Glide software, shedding light on the inhibitory mechanism. This investigation suggests that peptides derived from the P. martensii pearl matrix hold promise as a novel source for antihypertensive agents.

Enhancing the nutritional and bioactive benefits of faba bean flour by combining preprocessing and thermoplastic extrusion: A comprehensive study on digestion-resistant peptides

This research assessed how three preprocessing techniques [soaking (S), soaking and reconstitution (SR), and soaking and dehulling (SD)] impact the protein digestibility and bioactivity of faba bean flours when combined with thermoplastic extrusion. Samples were compared against a control (C) of extruded faba bean flour without preprocessing. Applying preprocessing techniques followed by extrusion diminished antinutrient levels while enhancing protein hydrolysis and in vitro bioactivity in higher extent compared to C. Specifically, SD combined with extrusion was the most effective, achieving an 80% rate of protein hydrolysis and uniquely promoting the release of gastric digestion-resistant proteins (50-70 kDa). It also resulted in the highest release of small peptides (<3kDa, 22.51%) and free amino acids (15.50%) during intestinal digestion. Moreover, while all preprocessing techniques increased antioxidant (ABTS radical-scavenging), antidiabetic, and anti-hypertensive activities, SD extruded flour displayed the highest levels of dipeptidyl peptidase inhibition (DPP-IVi, IC50=13.20 µg/mL), pancreatic α-amylase inhibition (IC50=8.59 mg/mL), and angiotensin I-converting enzyme inhibition (ACEi, IC50=1.71 mg protein/mL). As a result, it was selected for further peptide and in silico bioactive analysis. A total of 24 bioactive peptides were identified in intestinal digests from SD extruded flour, all with potential DPP-IVi and ACEi activities, and six were also predicted as antioxidant peptides. VIPAGYPVAIK and GLTETWNPNHPEL were highlighted as resistant bioactive peptides with the highest antidiabetic and antioxidant potential. Our findings demonstrated that combining preprocessing (particularly SD) and thermoplastic extrusion enhances protein digestibility in faba beans and promotes the release of beneficial bioactive peptides in the intestine.

The novel angiotensin-I-converting enzyme inhibitory peptides from Scomber japonicus muscle protein hydrolysates: QSAR-based screening, molecular docking, kinetic and stability studies

Food-derived angiotensin-converting enzyme-inhibitory (ACE-I) peptides have attracted extensive attention. Herein, the ACE-I peptides from Scomber japonicus muscle hydrolysates were screened, and their mechanisms of action and inhibition stability were explored. The quantitative structure–activity relationship (QSAR) model based on 5z-scale metrics was developed to rapidly screen for ACE-I peptides. Two novel potential ACE-I peptides (LTPFT, PLITT) were predicted through this model coupled with in silico screening, of which PLITT had the highest activity (IC50: 48.73 ± 7.59 μM). PLITT inhibited ACE activity with a mixture of non-competitive and competitive mechanisms, and this inhibition mainly contributed to the hydrogen bonding based on molecular docking study. PLITT is stable under high temperatures, pH, glucose, and NaCl. The zinc ions (Zn2+) and copper ions (Cu2+) enhanced ACE-I activity. The study suggests that the QSAR model is effective in rapidly screening for ACE-I inhibitors, and PLITT can be supplemented in foods to lower blood pressure.

Novel Multitarget ACE Inhibitory Peptides from Bovine Colostrum Immunoglobulin G: Cellular Transport, Efficacy in Regulating Endothelial Dysfunction, and Network Pharmacology Studies.

In this study, we used traditional laboratory methods, bioinformatics, and cellular models to screen novel ACE inhibitory (ACEI) peptides with strong ACEI activity, moderate absorption rates, and multiple targets from bovine colostrum immunoglobulin G (IgG). The purified fraction of the compound proteinase hydrolysate of IgG showed good ACEI activity. After nano-UPLC-MS/MS identification and in silico analysis, eight peptides were synthesized and verified. Among them, SFYPDY, TSFYPDY, FSWF, WYQQVPGSGL, and GVHTFP were identified as ACEI peptides, as they exhibited strong ACEI activity (with IC50 values of 104.7, 80.0, 121.2, 39.8, and 86.3 μM, respectively). They displayed good stability in an in vitro simulated gastrointestinal digestion assay. In a Caco-2 monolayer model, SFYPDY, FSWF, and WYQQVPGSGL exhibited better absorption rates and lower IC50 values than the other peptides and were thereby identified as novel ACEI peptides. Subsequently, in a H2O2-induced endothelial dysfunction (ED) model based on HUVECs, SFYPDY, FSWF, and WYQQVPGSGL regulated ED by reducing apoptosis and ROS accumulation while upregulating NOS3 mRNA expression. Network pharmacology analysis and RT-qPCR confirmed that they regulated multiple targets. Overall, our results suggest that SFYPDY, FSWF, and WYQQVPGSGL can serve as novel multitarget ACEI peptides.

Characterization of four new cycloartane triterpenoids from Swietenia macrophylla and their angiotensin-I-converting enzyme inhibitory activity

Angiotensin I-converting enzyme (ACE) inhibition is currently a common method for the treatment and control of hypertension. In this study, four new (1–4) and one known (5) cycloartane triterpenoids were isolated from the leaves of Swietenia macrophylla by chromatographic techniques and identified by their spectroscopic data and a comprehensive comparison of published data. The triterpenoids were evaluated for their ACE inhibitory potential using in vitro inhibition assays and in silico methods. The inhibition assay and enzyme kinetics results showed that the most active triterpenoid, compound 4, inhibited ACE in a mixed-type manner with an IC50 value of 57.7 ± 6.07 μM. Computer simulations revealed that compound 4 reduces the catalytic efficiency of ACE by competitive insertion into the active pocket blocking the substrate, and the binding activity occurs mainly through hydrogen bonds and hydrophobic interactions. The study showed that S. macrophylla can be a source of bioactive material and the ACE inhibitory triterpenoid could be a potential antihypertensive agent.

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.

Intravitreal ranibizumab injection is associated with an increased risk of chronic kidney disease: a population-based study in Taiwan.

Systemic vascular endothelial growth factor (VEGF) blockade has been the top adjunctive chemotherapy since 1990. Anti-VEGF therapy has also been associated with worsened renal function in some patients. However, the association between patient outcomes and use of intravitreal VEGF inhibitors remains controversial. Thus, it is necessary to determine the action mechanism and long-term renal effects of ranibizumab. The National Health Insurance Research Database (NHIRD) is one of the largest global databases that are extensively used for epidemiological research. NHIRD contains the medical information of all insureds, such as inpatient, outpatient, emergency, and traditional Chinese medicine records. We selected subjects aged ≥ 20years who recently administered ranibizumab for the ranibizumab cohort. Non-ranibizumab cohort consisted of subjects who did not receive ranibizumab, and the index date was a random date between 2008 and 2018. We excluded subjects with missing sex and age records and those in which the date of primary outcome was before the index date. The two cohorts were matched via 1:1 propensity score matching based on sex, age, index year, hypertension, diabetes mellitus, hyperlipidemia, stroke, coronary artery disease, alcoholism, chronic obstructive pulmonary disease, and age-related macular degeneration, retinal vein occlusion, and diabetic macular edema. Medical confounders were angiotensin I-converting enzyme inhibitors, statins, corticosteroids, VEGF inhibitors including bevacizumab and aflibercept, lithium, amphotericin B, adefovir, NSAIDS, cisplatin, and calcineurin inhibitors. Among 48,248 participants aged ≥ 20years, 24,136 (50%) received ranibizumab (13,565 male [56.20%] and 10,571 female [43.80%]). Moreover, 24,136 participants who did not receive ranibizumab were matched by age, sex, comorbidities, and medications. Subjects who received ranibizumab exhibited a significantly higher risk of CKD than those who did not receive ranibizumab (adjusted hazard ratio = 1.88, 95% CI = 1.79-1.96). Our findings revealed that exposure to intravitreal ranibizumab is an independent risk factor for CKD. Therefore, physicians and ophthalmologists should make the patients aware of such a correlation to increase patient safety and decrease the CKD burden.

Bioactive Peptides from Velvet Bean Tempe: Neutrase-Catalyzed Production in Membrane Reactor

Velvet beans are potential sources of parent proteins for bioactive peptide production. In this study, a combination of fermentation and neutrase-catalyzed continuous hydrolysis in an enzymatic membrane reactor was performed to produce antioxidative and angiotensin I-converting enzyme inhibitory (ACEi) peptides. The optimum operating conditions were τ = 6 h and [E]/[S] = 7.5%. The resulting permeate, which was a&lt;10-kDa fraction, exhibited antioxidant activity at 0.38 mg ascorbic acid equivalent antioxidant capacity (AEAC)/mL (2,2-diphenyl-1-picrylhydrazyl, DPPH inhibition) and 0.26 mg AEAC/mL (ferric reducing antioxidant power, FRAP), and ACEi activity of 81.02%. Further fractionation of the permeate increased the ACEi activity in which 2-kDa fraction showed the most potent activity (IC50 = 0.23 µg protein/mL). The IC50 value of the outcome was comparable to those reported in the literature for velvet bean-based peptides. Furthermore, this study suggests that neutrase is a good catalyst candidate for the synthesis of bioactive peptides from velvet beans.

Isolation and characterization of a new potential source of bioactive peptides: White mulberry (Morus alba) fruits and its leaves

In this study, white mulberry (WM; Morus alba L.) and its leaf (WML) were hydrolyzed using enzymes at different preheating temperatures (50, 60, 70, 80, and 90 °C) with distilled water at a ratio of 1:10 (w/v). Pepsin, trypsin, chymotrypsin, and alcalase were employed for enzymatic hydrolysis, aiming to investigate the impact of heat treatment and enzymatic hydrolysis on bioactive properties; in particular, angiotensin-converting enzyme-inhibitory (ACE-i) and antioxidant activities. The highest hydrolysis efficiency was observed when using pepsin. The smaller peptides with <3 kDa had better ACE-i and antioxidant activities in both WM and WML samples. Regarding antioxidant activity, the highest level was identified at a preheating temperature of 90 °C in the WM sample, and at preheating temperatures of 50 °C and without heating in the WML samples. In conclusion, heat treatment and enzymatic hydrolysis were found to be a positive impact on ACE-i and antioxidant activities under various conditions. Moreover, the proteins derived from WM and WML were rich in the sources of potential ACE-i and antioxidant peptides.

In Vitro Stability of ACE-Inhibitory Peptides of Rohu Fish Waste to Heat, pH and Gastrointestinal Enzymes

Angiotensin-I converting enzyme inhibitory (ACEi) peptides were prepared from rohu (Labeo rohita) fish wastes by enzymatic hydrolysis [1.1% alcalase concentration (v/w); 130 min time; 52°C temperature and 0.8:1 solid-liquid ratio]. Ultrasound Assisted Enzymatic Extraction (UAEE) and Microwave Assisted Enzymatic Extraction (MAEE) were performed to enhance degree of hydrolysis (DH), ACEi activity, and peptide yield (PY). The ACEi peptides were examined for stability during thermal processing, varied pH treatments and in vitro gastrointestinal digestion. Peptides were stable at different temperatures (25, 37, 55, 75, and 100°C) except at 121°C which reduced their stability by 7%, 6.9% and 2.2% in UAEE, MAEE and Non-Assisted Enzymatic Extraction (NAEE) peptides, respectively. Similarly, peptides retained ACEi at pH 2 to 8 and subsequent reduction at pH&gt;8. In vitro digestion studies showed stability of all peptides to GI digestion at 0.05% pepsin, 0.05% trypsin, 0.05% chymotrypsin and the combination of 0.025% trypsin and 0.025% chymotrypsin except MAEE peptides showing less stability with pepsin (0.05%). Therefore, it is concluded that these ACEi peptides derived from rohu fish waste, stable to heat, pH and gastrointestinal enzymatic action, can be used as ingredient in functional foods, which undergo thermal processing and digestion.

In silico screening and characterization, inhibition mechanism on ACE, and stability of antihypertensive peptides with Zn-chelating capacity identified from millet bran albumin hydrolysates

To obtain Angiotensin-I-Converting Enzyme (ACE) inhibition peptides with Zn-chelating capacity, millet bran albumin hydrolysates (MBAH) were subjected to Sephadex G-15 gel and reverse phase-high liquid performance chromatography, and UPLC-ESI-MS/MS analysis. Five oligopeptides including Val-Gly-Ser-Asp-Gly-Leu (VGSDGL), Thr-Gly-His-Gly-Val-Ala (TGHGVA), Gly-Cys-His-His-Tyr (GCHHY), Leu-Val-Glu-Ala-Val-Pro-Arg-Gly (LVEAVPRG) and Val-Leu-Ala-Gln-Glu-Glu (VLAQEE) were identified in MBAH. Of these, only pentapeptide GCHHY showed both ACE-inhibitory activity (IC50: 134.78 μmol/L) and Zn-chelating capacity (14.16 mg/g). Molecular docking and inhibition kinetics showed that GCHHY was a competitive inhibitor of ACE, because it could bind with Lys511 of ACE which belongs to the central S2 pocket. Moreover, GCHHY can affect zinc tetrahedral coordination in ACE through binding with Glu411 and His383. The sulfhydryl, amino and carboxyl groups of GCHHY can bind with zinc ions. Under the gastrointestinal digestion, the ACE-inhibitory activity of GCHHY was relatively stable, and the zinc solubility of GCHHY-Zn complexes was more stable than zinc sulfate (P < 0.05). In addition, both GCHHY and GCHHY-Zn complexes lowered the diastolic blood pressure and systolic blood pressure of spontaneous hypertensive rats at dose of 50–200 mg/kg body weight. These results suggested the potential applications of millet albumin peptides as ingredients for antihypertension or zinc fortification.

Discovery and Characterization of a Dual-Function Peptide Derived from Bitter Gourd Seed Protein Using Two Orthogonal Bioassay-Guided Fractionations Coupled with In Silico Analysis.

The hydrolysate of bitter gourd seed protein, digested by the combined gastrointestinal proteases (BGSP-GPs), exhibited the most potent inhibition on angiotensin-I-converting enzyme (ACE) with an IC50 value of 48.1 ± 2.0 µg/mL. Using two independent bioassay-guided fractionations, fraction F5 from reversed-phase chromatography and fraction S1 from strong cation exchange chromatography exhibited the highest ACE inhibitory (ACEI) activity. Three identical peptides were simultaneously detected from both fractions and, based on the in silico appraisal, APLVSW (AW6) was predicted as a promising ACEI peptide. Their dipeptidyl peptidase-IV (DPP4) inhibitory (DPP4I) activity was also explored. The IC50 values of AW6 against ACE and DPP4 were calculated to be 9.6 ± 0.3 and 145.4 ± 4.4 µM, respectively. The inhibitory kinetics and intermolecular interaction studies suggested that AW6 is an ACE competitive inhibitor and a DPP4 non-competitive inhibitor. The quantities of AW6 in BGSP-GP hydrolysate, fractions F5 and S1, were also analyzed using liquid chromatography-tandem mass spectrometry. Notably, AW6 could resist hydrolysis in the human gastrointestinal tract according to the result of the simulated gastrointestinal digestion. To the best of our knowledge, this is the first discovery and characterization of a dual-function (ACEI and DPP4I activities) peptide derived from bitter gourd seed protein.

The role of angiotensin I - converting enzyme (ACE) insertion/deletion gene polymorphism in hypertension and ACE inhibitor therapy: a narrative review

Primary hypertension is the most prevalent type of hypertension, which is primarily attributed to genetic factors. The angiotensin-converting enzyme (ACE) gene has emerged as a prominent candidate among the genetic factors influencing blood pressure regulation. The ACE gene encodes the ACE, which plays a crucial role in the renin-angiotensin system. The ACE gene insertion/deletion (I/D) polymorphism is a variation of the ACE gene that affects blood pressure regulation. Individuals with II, ID, and DD genotypes may exhibit distinct ACE plasma concentrations, potentially contributing to variations in blood pressure levels and response to ACE inhibitor therapy. This article aimed to provide a comprehensive overview of the relationship between the ACE I/D gene with hypertension and angiotensin-converting enzym inhibitor (ACEI) effectiveness. This article presents a narrative review encompassing relevant studies published between 2013 and 2023. A systematic search was conducted using reputable databases such as PubMed, Science Direct, and Scopus. Inclusion criteria were applied, resulting in the selection of 25 articles that met the predefined criteria. The analysis included 25 studies, comprising 5 articles that investigated the impact of ACEI therapy and 20 articles that examined the ACE I/D gene polymorphism in hypertensive populations without ACEI therapy. It can be concluded that compared to the I allele, the D allele of the ACE I/D gene is associated with a higher level of essential hypertension and a reduced ACEI response.

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.

Selection of goat β-casein derived ACE-inhibitory peptide SQPK and insights into its effect and regulatory mechanism on the function of endothelial cells

The angiotensin I-converting enzyme (ACE)-inhibitory peptide SQPK was selected by in silico digestion and virtual screening from goat β-casein, and its effect and regulatory mechanism on function of endothelial cells was further evaluated. The results showed that SQPK exhibited relatively good ACE inhibition capacity (IC50 = 452.7 μg/mL). Treatment with 25 μg/mL SQPK for 12 h significantly elevated nitric oxide (NO) production, stimulated eNOS expression (p < 0.05) and affected the transcriptomic profiling of EA. Hy926 cells. In particular, SQPK stimulated the expression of genes encoding inflammatory cytokines (CXCL1/2 and IL6) but depressed encoding mesenchymal markers (FN1 and CNN3). Furthermore, SQPK modified the expression of genes involved in endothelial-to-mesenchymal transition (EndMT). Therefore, the selected peptide SQPK may exert potential protective effects on the function of endothelial cells by inhibiting the EndMT.

Antihypertensive Effect, ACE Inhibitory Activity, and Stability of Umami Peptides from Yeast Extract.

Bioactive peptides from foods have garnered considerable attention as viable supplements for hypertensive patients. Herein, the antihypertensive effect and mechanism of umami peptides from yeast extract were investigated based on the pharmacophore model, simulated digestion, spontaneously hypertensive rat (SHR) model, and molecular docking. Notably, umami peptide LLLLPKP exhibited favorable angiotensin I-converting enzyme (ACE) inhibitory activity (IC50 = 10.22 μM) in vitro and regulated blood pressure in the SHR model with excellent durability. Remarkably, LLLLPKP showed the highest Fitvalue (4.022) of the pharmacophore model, indicating its similar pharmacological effects as ACE inhibitors. During the simulated gastrointestinal digestion, the ACE inhibition rate of LLLLPKP was merely reduced by 5.89%, but it was enzymatically cleaved into 14 peptide segments. The C-terminal sequence comprising L (4), P (5), K (6), and P (7) exhibited robust stability and a notable presence within the peptide segments postdigestion. Meanwhile, according to molecular docking, these four residues within LLLLPKP were responsible for all interactions with key sites within active pockets S1 and S2 and the active pocket of Zn2+. In light of these findings, LLLLPKP is a highly promising antihypertensive peptide. Developing this umami peptide with antihypertensive effects holds substantial importance for the long-term treatment of hypertension.