Angiotensin-converting Enzyme Inhibition Research Articles

Immunogenicity of bivalent versus monovalent mRNA booster vaccination among adult paramedics in Canada who had received three prior mRNA wild-type doses.

Introduction. Comparative immunogenicity from different mRNA booster vaccines (directed at WT, BA.1 or BA.4/5 antigens) remains unclear. Methods. We included blood samples from adult paramedics who received three mRNA WT-directed vaccines plus a fourth dose of the following: (1) WT monovalent, (2) Moderna BA.1-WT bivalent or (3) Pfizer BA.4/5 WT bivalent vaccine. The primary outcome was angiotensin-converting enzyme 2 (ACE2) inhibition to BA.4/5 antigen. We used optimal pair matching (using age, sex-at-birth, preceding SARS-CoV-2 infection and fourth vaccine-to-blood collection interval) to create balanced groups to individually compare each vaccine type to each other vaccine (overall, within subgroups defined by SARS-CoV-2 infection and after combining BA.1 and BA.4/5 cases). We compared outcomes with the Wilcoxon matched-pairs signed rank test. Results. Overall, 158 paramedics (mean age 45 years) were included. ACE2 inhibition was higher for BA.1 compared to WT (P=0.002); however, no difference was detected between BA.4/5 vs. WT or BA.1 vs. BA.4/5. Among cases with preceding SARS-CoV-2, there were no detected between-group differences. Among cases without preceding SARS-CoV-2, the only detected difference was BA.1>WT (P=0.003). BA.1 and BA.4/5 cases combined had higher ACE2 inhibition than WT (P=0.003). Conclusion. Omicron-directed vaccines appear to improve Omicron-specific immunogenicity; however, this appears limited to SARS-CoV-2-naive individuals.

BMY 7378, a selective α1D-adrenoceptor antagonist, is a new angiotensin converting enzyme inhibitor: In silico, in vitro and in vivo approach

BMY 7378 is a multitarget drug primarily known for its selective antagonism of α1D-adrenoceptors (α1D-AR), exhibiting both hypotensive effects and the ability to prevent or reverse angiotensin II-induced vascular hypertrophy. Notably, BMY 7378 contains a phenylpiperazine moiety, a structural feature associated with angiotensin-converting enzyme (ACE) inhibition. This study aimed to investigate ACE inhibition as a potential pharmacological mechanism of BMY 7378. Using an in silico approach we predicted BMY 7378 interactions with the ACE active site, followed by in vitro activity assays. Additionally, ACE protein expression in the heart was analyzed following four weeks of BMY 7378 treatment in 7–8-month-old spontaneously hypertensive rats (SHR). All assays were benchmarked against captopril, a standard ACE inhibitor. In silico results showed that BMY 7378 binds to the ACE active site, though with reduced interaction with Zn701 (73.7 % compared to captopril), likely due to the pKa of its amino group. The inhibitory concentration 50 (IC50) for BMY 7378 was 136 μM, lower than other reported phenylpiperazine derivatives. Furthermore, BMY 7378 significantly increased ACE expression in the hearts of SHR, with an increase of 8.5-fold compared to captopril. In conclusion, BMY 7378 exhibits dual activity as an α1D-AR antagonist and an ACE inhibitor, making it a promising pharmacological tool for investigating and potentially treating hypertension and its associated cardiovascular complications.

Molecular Docking and Antihypertensive Activity of Eupalitin 3-O-β-D-galactopyranoside Isolated from Boerhavia diffusa Linn.

Background: Angiotensin-converting enzyme (ACE) is a key regulator of blood pressure, and ACE inhibition is an essential part of the treatment of hypertension. We used a molecular docking approach to find the interaction of ACE with an active flavonoid isolated from Boerhavia diffusa Linn, eupalitin 3-O-β-D-galactopyranoside, which leads to potential antihypertensive effects in methyl predenisolone-induced hypertensive rats. Additionally, the pharmacokinetic parameters of this compound are assessed. Methods:eupalitin-3-O-β-D-galactopyranoside was isolated from leaves of Boerhavia diffusa by sedimentation method. The compound was characterized by UPLC-MSMS, NMR, and UV spectroscopy to confirm the identity of the compound. Hypertension was induced in rats with methyl predenisolone (5 mg/kg/day) for 14 days. Systolic and diastolic blood pressure effects of eupalitin 3-O-β-D-galactopyranoside were assessed using a tail-cuff method. The blood plasma data for oral administration were used to determine various pharmacokinetic parameters from the bioavailability and serum concentration. Results: In methyl predenisolone-induced hypertensive rats, both systolic and diastolic blood pressures were significantly lower than that of the vehicle with treatment from eupalitin 3-O-β-D-galactopyranoside (p < 0.01). Conclusions: The pharmacokinetic process showed the moderate bioavailability of the compound; eupalitin 3-O-β-D-galactopyranoside induces powerful antihypertensive activity in methyl predenisolone-induced hypertensive rats, implying potential clinical application as a new therapeutic drug for hypertension.

Effect of Acid Whey Protein Concentrate on the Rheological Properties, Antioxidant Capacities, and Biological Activities of Bioaccessible Fractions in Fermented Camel Milk.

The production of set-type camel milk yogurt is challenging due to its unique physicochemical properties, which differ from those of other milk species. The present study aimed to evaluate the effects of camel milk supplementation with different levels (0, 3, and 6%) of whey protein concentrate (WPC) on the texture, rheological properties, antioxidant capacity, and biological activity of camel milk yogurt compared with bovine milk (BM) yogurt. These characteristics were evaluated before and after in vitro digestion of yogurt samples after 1 and 15 d of storage at 4°C. The results show that using WPC, particularly at 6% (WPCA6), significantly affected the characteristics of yogurt. The water-holding capacity increased by increasing the level of WPC and showed higher values than BM yogurt. Furthermore, the adhesiveness in yogurt samples containing 6% of WPC was significantly higher than other treatments, representing 6.3 and 6.1 mJ after 1 and 15 d, respectively. The apparent viscosity of WPCA6 was also higher than other yogurt treatments at different shear rates throughout storage, indicating a thicker and more viscous yogurt. Camel milk yogurt showed higher DPPH values, representing 74.1, 71.6, and 78.1% for WPCA0, WPCA3, and WPCA6, respectively, compared with BM yogurt (22.9%). The biological activities, including α-amylase, α-glucosidase, and angiotensin-converting enzyme inhibitions, increased after in vitro digestion of yogurt samples. Principal component analysis underscored the distinct bioactive profile of WPCA6, distinguishing it from other yogurt treatments and highlighting its superior properties.

Exploring the antihypertensive potential of natural compounds from Zygophyllum sp plant: An in-silico investigation of ACE inhibition

Abstract Hypertension, a major contributor to global mortality, requires comprehensive management including lifestyle changes and medication. This study explores the potential of natural compounds from Zygophyllum sp as Angiotensin-converting enzyme (ACE) inhibitors, a key class of antihypertensive drugs. Using molecular docking methodology, we investigated the inhibitory effects of these compounds on the ACE enzyme (PDB: 1UZF). Our work demonstrated that several molecules exhibited promising binding scores compared to established reference ligands, suggesting potential ACE-inhibiting properties. Myristic acid showed the most favorable score (-9.2454 kcal/mol), surpassing conventional reference drugs. Geranyllinalool, Pseudophytol, Methyl linoleate and Phytol also demonstrated superior scores. 1-Octadecene and linoleic acid outperformed captopril and aligned closely with other reference ligand scores. The computational scores, largely exceeding those of established drugs, indicate strong affinities between Zygophyllum sp ’ s chemical constituents and the ACE enzyme. This suggests potential antihypertensive properties of the plant and its bioactive components, supporting its traditional use as an antihypertensive remedy. The notable efficacy scores of select known therapeutic agents further validate this potential. However, additional in-vitro and in-vivo investigations are necessary to robustly establish the ACE-inhibitory capability of Zygophyllum sp compounds. This study provides a foundation for further research into natural antihypertensive treatments, potentially offering new avenues for managing this widespread health concern.

Antihypertensive peptides from hydrolyzed proteins of Pleurotus spp.: production, in vitro digestion and identification

This study aimed to investigate in vitro antihypertensive property of protein hydrolysates from Pleurotus spp. mushrooms obtained through enzymatic hydrolysis. FlavourzymeTM 500L, AlcalaseTM 2.4L and NeutraseTM 0.8L were used alone and in combination using an experimental design of mixtures. Antihypertensive activity was determined by angiotensin-converting enzyme (ACE) inhibition and the simulated in vitro digestion was performed according to the INFOGEST protocol. Results showed that most of the protein hydrolysates obtained displayed higher ACE inhibitory activity than non-hydrolyzed protein, ranging from 15.76% and 50.87% inhibition. The highest ACE inhibition and the lowest TCA soluble protein content (52.09%) were detected for the protein hydrolysates obtained by using the binary mixture of FlavourzymeTM 500L and AlcalaseTM 2.4L in equal proportions. Hydrolysis kinetics showed no significant difference in ACE inhibitory activity between 20 and 120minutes of enzymatic reaction. The fraction with molecular weight between 3 and 5kDa obtained after ultrafiltration showed the most contribution for ACE inhibitory activity (47% inhibition). After simulated digestion, the hydrolysates maintained a significant ACE inhibition capacity, indicating the resistance of the peptides to the action of gastrointestinal enzymes. Through proteomic analysis, 26 peptides were identified and the sequences LPILP, IPLLP, PLLPQ and VIQYDPPQ were considered potentially antihypertensive.

Molecular insights into the inhibition of angiotensin-converting enzyme 1 by hemopressin peptides

Inhibiting angiotensin-converting enzyme 1 (ACE1) is a key strategy for managing hypertension as it prevents the formation of angiotensin II, a potent vasoconstrictor. Given the adverse effects associated with synthetic inhibitors, there is an increasing focus on exploring natural bioactive peptides as potential ACE1 inhibitors. Hemopressins (Hp) are peptides derived from hemoglobin. The present study investigated the ACE1 inhibitory activity of two Hp variants, Hp bearing phenylalaine (Hp-F) and Hp bearing leucine (Hp-L), using a combination of in vitro and in silico methodologies. In enzyme inhibition assays, Hp-L variants exhibited better inhibition when compared to Hp-F variants. Furthermore, in molecular docking and molecular dynamics simulations, Hp-L variants displayed favorable binding characteristics, in terms of binding energy and interactions, supporting their potential to be effective ACE1 inhibitors. The peptides were observed to interact with key residues involved in binding widely used ACE1 inhibitors. Notably, peptide RVD-Hp-L (RVDPVNFKLLSH) showed the lowest IC50 value, higher binding affinity and sustained interactions while binding to the catalytic site of ACE1. Finally, the substitution of phenylalanine with leucine in hemopressins significantly enhances their binding affinity and inhibitory potency.

Oat-Protein-Based Diet Lowers Blood Pressure and Prevents Cardiac Remodeling and Dysfunction in Spontaneously Hypertensive Rats.

Background/Objectives: Hypertension and its associated complications, such as cardiac remodeling and dysfunction, continue to impose a significant burden on global healthcare. Nutritional interventions have been recognized as playing a crucial role in addressing this devastating condition termed a 'silent killer'. Plant-based proteins could potentially be utilized as a non-pharmacological strategy to combat hypertension and its related risk factors. In this study, we investigated the efficacy of an oat protein diet in managing hypertension and cardiac abnormalities. Methods: Four-week-old male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were fed a regular diet with casein as a protein source or an oat-protein-based diet for 16 weeks. Twenty-week-old male SHRs showed high blood pressure (BP), cardiac remodeling, cardiac dysfunction, higher levels of markers of oxidative stress [malondialdehyde (MDA)] and inflammation [tumor necrosis factor-α (TNF-α)], as well as lower levels of a marker of vascular function (nitric oxide). Results: The oat protein diet was able to significantly lower high BP, prevent cardiac remodeling and dysfunction, improve the levels of nitric oxide, and reduce the levels of TNF-α. Oat protein, after in vitro gastrointestinal digestion, also exhibited angiotensin-converting enzyme inhibition and significantly higher antioxidant activity than casein when assessed with the 2,2-diphenyl-1-picrylhydrazyl and the iron-chelating assays in vitro.Conclusions: oat protein lowers BP and prevents cardiac remodeling and dysfunction partly via improving the levels of nitric oxide and TNF-αin SHRs. Its high antioxidant potential could contribute to the observed cardiovascular effects.

Uncovering the Potential Somatic Angiotensin-Converting Enzyme (sACE) Inhibitory Capacity of Peptides from Acheta domesticus: Insights from In Vitro Gastrointestinal Digestion.

Entomophagy is being proposed as a sustainable and nutritious alternative protein source. Additionally, insect consumption is also associated with some health benefits mediated by bioactive compounds produced during gastrointestinal (GI) digestion. The antihypertensive property resulting from the inhibition of the somatic angiotensin-converting enzyme (sACE) by small peptides is one of the most common bioactivities related to insect consumption. This study aimed to investigate the potential sACE-inhibitory capacity of six peptides (AVQPCF, CAIAW, IIIGW, QIVW, PIVCF, and DVW), previously identified by the in silico GI digestion of Acheta domesticus proteins, validate their formation after in vitro GI digestion of A. domesticus by LC-MS/MS, and assess the bioactivity of the bioaccessible digesta. The results showed that the IC50 values of AVQPCF, PIVCF, and CAIAW on sACE were 3.69 ± 0.25, 4.63 ± 0.16, and 6.55 ± 0.52 μM, respectively. The obtained digesta demonstrated a sACE-inhibitory capacity of 77.1 ± 11.8 µg protein/mL extract (IC50). This is the first report of the sACE-inhibitory capacity attributed to whole A. domesticus subjected to GI digestion without any pre-treatment or protein concentration. This evidence highlights the potential antihypertensive effect of both the digesta and the identified peptides.

Comparing the anti-remodeling effect of sacubitril/valsartan and angiotensin-converting enzyme inhibition on myocardial samples of advanced heart failure patients undergoing heart transplantation

Abstract Background In decreasing heart failure (HF) hospitalization and cardiovascular death in HF patients with reduced ejection fraction, Sacubitril/Valsartan (SAC/VAL) treatment was proved to be superior to angiotensin-converting enzyme inhibition (ACEi). According to recent experimental results and clinical data based on echocardiography and circulating biomarkers, this benefit might be at least partially attributed to a greater anti-remodeling effect. However, there is a lack of direct evidence from human myocardial samples for this assumption. Purpose Therefore, we aimed to compare the anti-remodeling effect of SAC/VAL treatment to ACEi on myocardial samples of HF patients undergoing heart transplantation (HTX). Methods We studied left ventricular (LV) samples of seventy advanced HF patients who underwent HTX and received either SAC/VAL (SAC/VAL group, N=32) or ACEi treatment (ACEi group, N=38) for at least three months prior to HTX. Furthermore, all patients received beta-blockers and mineralocorticoid receptor antagonists titrated to maximally tolerated or target dose. Our groups were matched for age, sex, ejection fraction and other clinical parameters. Patients with liver or kidney failure, mechanical circulatory support, systemic inflammatory/fibrotic diseases or positive inotrope treatment were excluded. Myocardial mRNA expression of fibrotic markers and B-type natriuretic peptide (BNP) were measured with qRT-PCR and normalized to glyceraldehyde 3-phosphate dehydrogenase expression. Interstitial fibrosis area was assessed histologically. Results Preoperative plasma N-terminal pro-BNP levels were similar in the two groups (SAC/VAL: 4363±752 pg/mL vs. ACEi: 4616±1020 pg/mL; p=0.911). In contrast, the mRNA level of BNP in the myocardium was lower in patients treated with SAC/VAL (SAC/VAL: 2.2±1.05 vs. ACEi: 5.2±1.74; p=0.006). TIMP metallopeptidase inhibitor 1 (SAC/VAL: 0.07±0.01 vs. ACEi: 0.13±0.02; p=0.011), TIMP metallopeptidase inhibitor 2 (SAC/VAL: 0.06±0.01 vs. ACEi: 0.11±0.01; p&amp;lt;0.001), collagen type I alpha 1 chain (SAC/VAL: 0.02±0.00 vs. ACEi: 0.08±0.02; p&amp;lt;0.001) and collagen type III alpha 1 chain (SAC/VAL: 0.12±0.02 vs. ACEi: 0.27±0.04; p&amp;lt;0.001) relative gene expressions were also decreased in the LV of SAC/VAL-treated patients. Histology analysis confirmed reduced interstitial myocardial fibrosis area in the SAC/VAL group as well (SAC/VAL: 7.2±0.4% vs. ACEi: 8.6±0.5%; p=0.031). Conclusions SAC/VAL treatment decreased the myocardial expression of BNP and fibrosis-related genes to a greater extent compared with ACEi in LV samples of patients undergoing HTX. Histological analysis also verified the differences in fibrosis. Thus, the anti-remodeling effect of SAC/VAL might be superior to ACEi even in advanced HF.

Temporal trends and regional differences of initial oral antiarrhythmic drug options in patients with new-onset atrial fibrillation: a report from the GLORIA-AF registry

Abstract Background New-onset atrial fibrillation (AF) is common and antiarrhythmic drugs (AADs) are commonly used for treating such patients. However, whether there are temporal changes and regional differences in the choice of AADs in direct acting non-vitamin K oral anticoagulants (DOACs) era is less studied. Purpose The present study aimed to analyze the temporal trends and regional differences of initial oral AAD options in patients with new-onset AF in the GLORIA-AF registry, based on a proposed modernized classification of AADs in 2018 (Circulation, 2018, PMID: 30354657). AADs involved in the present study included traditional Vaughn-Williams Class I to Class IV AAD, Class IId AAD (digoxin), and Class VII AAD, which acts on the upstream of arrhythmia including angiotensin converting enzyme inhibition, angiotensin receptor blocker, and stains. Methods Temporal changes regarding the AAD use between the two phases of GLORIA-AF and regional differences of AADs choice were investigated. Factors associated with the choice of different AADs were established by multivariate logistic regression. Results Among the 36,617 participants in the GLORIA-AF registry, 33,208 (90.7%) were prescribed with AADs: 74.0% were rate control and 10.2% were rhythm control, and among the prescribed AADs, single and dual AADs were used in 73.3% and 24.9%, respectively. Moreover, 70.5% patients received upstream target modulators (Class VII AAD). Class IIa AADs (beta-blockers) were the most commonly prescribed AAD and slightly increased from Phase II (60.58%) to Phase III (62.91%) while the use of Class IId AAD (e.g. digoxin) decreased regardless of single or combined use. AADs use varied significantly among regions but the temporal trends and regional differences were similar with that of the overall cohort. Age, gender, comorbidities, admission signs, region, and concomitant medications (e.g. anticoagulants) were associated with the choices of different AADs. Conclusions In the DOAC era, new-onset AF patients receiving AAD commonly included upstream therapy. Rate control was still the dominant strategy for patients with new-onset AF but the use of Class IId AAD significantly decreased with the increased use of Class IIa AAD. The choice of AADs demonstrated significant regional differences and concomitant anticoagulants played important roles.Temporal trends in GLORIA-AFComparisons of AADs use in GLORIA-AF

Goat Milk Protein-Derived ACE Inhibitory Peptide SLPQ Exerts Hypertension Alleviation Effects Partially by Regulating the Inflammatory Stress of Endothelial Cells.

Hypertension has always posed a severe threat to people's health. Food-derived angiotensin-converting enzyme (ACE)-inhibitory peptides have the potential to both prevent and treat hypertension. In the current investigation, two ACE-inhibitory peptides (SLPQ and PYVRYL) from goat milk were studied for their endothelial effects using EA.hy926 cells. PYVRYL outperformed SLPQ, yet neither impacted cell survival below 200 μg/mL. Investigation of SLPQ's impact on EA.hy926 cell expression revealed 114 differentially expressed genes, with 65 downregulated and 49 upregulated. The genes were enriched in cytokine interactions, coagulation cascades, Hippo signaling, and ECM-receptor interaction. Decreased c-x-c motif chemokine ligand 2 (CXCL2), integrin subunit beta 2 (ITGB2), and fbj murine osteosarcoma viral oncogene homologue (FOS) expression and increased secreted phosphoprotein 1 (SPP1) expression may protect endothelial cells from inflammation. Our findings suggest that beyond ACE inhibition, SLPQ aids blood pressure control by influencing endothelial function, paving the way for its use as an antihypertensive food ingredient.

Identification of Structure-Linked Activity on Bioactive Peptides from Sea Cucumber (Stichopus japonicus): A Compressive In Silico/In Vitro Study.

A sea cucumber (Stichopus japonicus) is an invertebrate rich in high-quality protein peptides that inhabits the coastal seas around East Asian countries. Such bioactive peptides can be utilized in targeted disease therapies and practical applications in the nutraceutical industry. Bioactive peptides were isolated from Stichopus japonicus through ultrafiltration and Sephadex G-10 size exclusion chromatography. The low-molecular-weight fraction (ACSH-III) showed the highest hydroxyl radical scavenging and angiotensin-converting enzyme (ACE) inhibitory activities. Subsequent purification of ACSH-III resulted in four fractions, of which ACSH-III-F3 and ACSH-III-F4 exhibited significant bioactivity. Peptides identified in these fractions, including Phenylalanine-Proline-Threonine-Tyrosine (FPTY) and Tyrosine-Proline-Serine-Tyrosine-Proline-Serine (YPSYPS), were characterized using high-performance liquid chromatography (HPLC) and quadrupole time-of-flight mass spectrometry (QTOF-MS). FPTY demonstrated the most potent antioxidant and antihypertensive activities among these peptides, with IC50 values of 0.11 ± 0.01 mg/mL for hydroxyl radicals and 0.03 ± 0.01 mg/mL for ACE inhibition. Docking simulations revealed strong binding affinities of these peptides to the active site of the ACE, with FPTY displaying interactions similar to those of the synthetic inhibitor lisinopril. These findings suggest that the identified peptides, particularly FPTY, have potential applications as natural antioxidants and functional foods.

Research on the Synergistic Inhibition of Angiotensin-Converting Enzyme (ACE) by the Gastrointestinal Digestion Products of the ACE Inhibitory Peptide FPPDVA.

To gain a deeper understanding of the ACE inhibition effect, the inhibitory effect of ACE-inhibiting peptide (ACEIP) FPPDVA's digestive products on ACE was further investigated. Two novel peptides, PD (IC50 = 161.1 ± 1.10 μM) and DV (IC50 = 66.51 ± 0.99 μM) were identified in the digestive products of FPPDVA using LC-MS/MS. The Peptide Mix (FPPDVA, PD, and DV) exhibited a remarkable synergistic effect on ACE inhibition by significantly enhancing it by up to 508% compared to the individual peptides alone. Furthermore, theoretical simulations suggest that the Peptide Mix synergistically inhibits ACE activity by forming more stable complexes with the active site of ACE, facilitated by an increased number of hydrogen bonds. Additionally, Lineweaver-Burk plot analysis and spectroscopic studies further verified the presence of these stable complexes. ITC results show that the combination of Peptides Mix and ACE is a spontaneous exothermic process driven by entropy. The study showed that FPPDVA has a stronger inhibitory effect on ACE after digestion, making it suitable as an antihypertensive peptide in functional foods.

Deciphering angiotensin converting enzyme 2 (ACE2) inhibition dynamics: Carnosine's modulatory role in breast cancer proliferation – A clinical sciences perspective

BackgroundAngiotensin-converting enzyme 2 (ACE2) is a pivotal molecular nexus linking novel coronavirus disease to breast cancer. In-silico investigations have repurposed carnosine for both these conditions based on its potential ACE2 inhibitory properties. MethodsUtilizing an ACE2 inhibitor screening kit, we determined the inhibitory range of carnosine doses. Subsequently, we examined the effect of carnosine on ACE2 expression in supernatants from various breast cancer cell lines (MCF-7, MDA-MB-231, and EMT-6). Additionally, we compared ACE2 activity in cell line pellets with and without carnosine and a putative ACE2 activator using a fluorometric activity assay kit. Finally, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay across overlapping concentrations. ResultsCarnosine exhibited dose-dependent ACE2 inhibition within the 100–300 mM range. ACE2 expression significantly diminished after exposure to carnosine for 2 and 24 h in MDA-MB-231 and MCF-7 cell lines, respectively. MTT assay unveiled notable antiproliferative effects in MDA-MB-231 (50 % survival at approximately 265 mM) and EMT-6 cell lines (unquantifiable 50 % survival dose). Conversely, the MCF-7 cell line displayed a modest increase in proliferation (Effective concentration 50–186 mM, ∼40 % increased survival). ConclusionThis pioneering study delineates evident dose-dependent ACE2 inhibition by carnosine. Moreover, it unveils the modulatory impact of this ACE2 inhibitor in breast cancer cell lines. Carnosine demonstrated a significant antiproliferative effect on aggressive cell lines while sparing luminal cell lines from substantial toxic or proliferative effects.

The profile of plant bioactive compounds in Xinjiang, China unifloral safflower honey and their inhibitory on ACE, and determination of the mechanism of inhibition

Investigating the plant bioactive compounds in unifloral safflower honey from Xinjiang, China, is helpful for verifying its botanical origin and evaluating its functional properties. Therefore, this study quantifying hydroxysafflor yellow A (HSYA), anhydroxysafflor yellow B (ASYB), quercetin, kaempferol, rutin, myricetin, hyperoside, gallic acid, quinic acid, and ferulic acid in safflower honey by high-performance liquid chromatography; HSYA and ASYB accounted for 16.12–28.83% and 13.63–33.09%, respectively, of the quantified plant bioactive compounds and were considered characteristic markers for authentication. These compounds also exhibit angiotensin converting enzyme (ACE) inhibitory activity; the IC50 ranges from 13.33 to 132.45 μmol L−1, and the inhibition constant (Ki) is between 17.13 and 121.34 μmol L−1. HSYA (IC50 = 20.24 μmol L−1, Ki = 19.63 μmol L−1) and ASYB (IC50 = 19.33 μmol L−1, Ki = 17.13 μmol L−1) exhibited the strongest inhibitory effects. Molecular simulation studies have shown that these bioactive compounds bind key residues in the active pocket of ACE through hydrogen bonding and hydrophobic interactions, leading to ACE inhibition. Overall, HSYA and ASYB could be considered bioactive chemical markers for verifying the botanical origin of Xinjiang, China, unifloral safflower honey, and safflower honey may be a potential functional food by inhibiting ACE.

Bioactive Peptides from Corn (Zea mays L.) with the Potential to Decrease the Risk of Developing Non-Communicable Chronic Diseases: In Silico Evaluation.

Studies have shown that corn (Zea mays L.) proteins, mainly α-zein, have the potential to act on therapeutic targets related to non-communicable chronic diseases, such as high blood pressure and type 2 diabetes. Enzymatic hydrolysis of proteins present in foods can result in a great diversity of peptides with different structures and possible bioactivities. A review of recent scientific research papers was performed to show evidence of the bioactive properties of corn peptides by in vitro assays. The α-zein amino acid sequences were identified in the UniProtKB protein database and then analyzed in the BIOPEP database to simulate enzymatic digestion and verify the potential biological action of the resulting peptides. The peptides found in the BIOPEP database were categorized according to the probability of presenting biological action using the PeptideRanker database. The aim was to use existing data to identify in silico the potential for obtaining biologically active peptides from α-zein, the main storage protein of corn. The analysis showed that the majority of peptide fragments were related to the inhibition of angiotensin-converting enzyme, followed by the inhibition of dipeptidyl peptidase IV and dipeptidyl peptidase III. Many drugs used to treat high blood pressure and type 2 diabetes work by inhibiting these enzymes, suggesting that corn peptides could be potential alternative agents. In vitro studies found that the primary bioactivity observed was antioxidative action. Both in vitro and in silico approaches are valuable for evaluating the bioactive properties resulting from protein hydrolysis, such as those found in α-zein. However, conducting in vitro studies based on prior in silico evaluation can be more efficient and cost-effective.

Bioactive Properties of Enzymatic Gelatin Hydrolysates Based on In Silico, In Vitro, and In Vivo Studies.

This current study aims to analyze the potential bioactivities possessed by the enzymatic hydrolysates of commercial bovine, porcine, and tilapia gelatins using bioinformatics in combination with in vitro and in vivo studies. The hydrolysate with superior inhibition of angiotensin converting enzyme (ACE) activity was used to treat the D-galactose (DG)-induced amnesic mice. In silico digestion of the gelatins led to the identification of peptide sequences with potential antioxidant, ACE-inhibitory, and anti-amnestic properties. The results of in vitro digestion revealed that the <1 kDa peptide fraction of porcine gelatin hydrolysate obtained after 1 h digestion with papain (PP) (PP1, <1 kDa) potently inhibited ACE, acetylcholinesterase, and prolyl endopeptidase activities at 87.42%, 21.24%, and 48.07%, respectively. Administering the PP1 to DG-induced amnesic mice ameliorated the spatial cognitive impairment and Morris water maze learning abilities. The dentate area morphology in the PP1-treated mice was relatively similar to the control group. In addition, PP1 enhanced the antioxidant capacity in the DG-induced amnesic mice. This study suggests that PP1 could serve as a potential treatment tool against oxidative stress, hypertension, and neurodegenerative diseases.

Antihypertensive mechanism of the medicine food homology compound solution with high ACE inhibition rate based on network pharmacology and molecular docking

Certain instances of medicine food homology (MFH) have an antihypertensive effect, which has a therapeutic effect on hypertension, but their mechanism in treating hypertension and improving blood pressure is still unclear. The objective of this study is to analyze the potential bioactive substances and the hypotensive mechanism by which the MFH compound solution (Hawthorn:Lycium barbarum:Cassia = 4:1:1) with a high angiotensin-converting enzyme (ACE) inhibition rate. This will be achieved through the use of network pharmacology and molecular docking techniques, which will be further validated through experimental testing. The key components in the MFH compound solution were obtained by constructing the component-disease target network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to explore the pathways of the MFH compound solution participating in anti-hypertension. The content of the main active ingredients in the MFH compound solution was identified by high-performance liquid chromatography (HPLC). The main active components were quercetin, beta-sitosterol, stigmasterol, kaempferol, and isorhamnetin, while the identified core genes were AKT1 and TP53. Through pathway analysis, the mechanisms of the MFH compound solution against hypertension may be Lipid and atherosclerosis, Calcium signaling pathway, PI3K-AKT signaling pathway, etc. Moreover, the molecular docking of five key compounds and the top five targets verified the reliability of network pharmacology results. HPLC analysis revealed that these five active substances were detected in the MFH compound solution, where kaempferol was the most abundant. This study revealed that the MFH compound exerted a hypotensive effect through multiple targets and pathways.

Evaluation of Prebiotic and Health-Promoting Functions of Honeybee Brood Biopeptides and Their Maillard Reaction Conjugates.

This study addresses the growing interest in natural functional ingredients by evaluating the prebiotic and health-promoting functions of honeybee brood biopeptides (HBb-Bps) and their conjugates. The purpose was to investigate their antioxidant activities, enzyme inhibition properties, and effects on probiotic growth and short-chain fatty acid (SCFA) production. The HBb-Bps were conjugated with honey, glucose, and fructose via the Maillard reaction. Antioxidant activities were assessed using DPPH and ABTS assays. The inhibitory effects on amylase, pancreatic lipase, and the angiotensin-converting enzyme (ACE) were measured. Probiotic growth and SCFA production were evaluated using L. plantarum TISTR846, and L. lactis TISTR1464. The HBb-Bps and their conjugates exhibited enhanced antioxidant activities post-Maillard reaction. They showed moderate enzyme inhibition, which decreased after conjugation. However, ACE inhibition increased with conjugation. The HBb-Bps significantly promoted probiotic growth and SCFA production, with further enhancement by the Maillard reaction. Overall, the HBb-Bps and their conjugates demonstrate significant prebiotic and health-promoting functions, suggesting their potential as natural ingredients in functional foods and nutraceuticals. Further research should focus on the in vivo effects and, given their solubility and stability these biopeptides could be incorporated into functional food formulations, such as health beverages, protein bars, and other fortified foods designed to deliver specific health benefits.