Angiotensin I-converting Enzyme Inhibitor Research Articles

Study of the Phenolic Compounds and Biological Activities of the Wild Fruits of Vaccinium leucanthum Schltdl.

Around 450 species of blueberries of the genus Vaccinium are known, of which some have gained preferential breeding, such as the ‘Biloxi’ variety. Some little studied species, such as Vaccinium leucanthum Schltdl. located in Mexico, could be a potential source of bioactive compounds. In this study, the phenolic compounds (chlorogenic acid content, hyperoside, phenols, flavonoids, tannins and total anthocyanins content) as well as the potential biological activity (antioxidant, antimicrobial, xanthine oxidase converting enzyme inhibition and angiotensin I inhibition) of Vaccinium leucanthum Schltdl. were studied, making a comparison with the Biloxi variety, which is the most widely cultivated one. The extract of V. leucanthum showed the highest content of flavonoids (4.853 ± 0.341 mg QE/g DW), total anthocyanins (0.303 ± 0.008 mg CGE/g DW), petunidin-3-glucoside (6.92 ± 0.12 mg PGE/g DW), malvidin-3-glucoside (11.80 ± 0.10 mg MGE/g DW) and hyperoside (5.137 ± 0.100 mg HE/g DW). It should be noted that V. leucanthum showed the same total tannin content and the same efficacy in the inhibition of Angiotensin I-converting enzyme as ‘Biloxi’, as well as the same antibacterial effect against the enterobacteria Salmonella choleraesuis ATCC 12022, Escherichia coli ATCC 12792and Shigella flexneri ATCC 10708. These findings demonstrate that V. leucanthum extracts could be an important source of preservatives as well as nutraceutical compounds for use in foods and medicines.

Thermal Compatibility of New ACEI Derivatives with Popular Excipients Used to Produce Solid Pharmaceutical Formulations.

Background/Objectives: Increasing drugs' stability and adequately protecting them against degradation will ensure a decrease in their price and broader availability of pharmaceutical substances. This is of great importance, especially for drugs used to treat the most common diseases in the population, such as hypertension. The study examined two newly synthesized substances from the angiotensin I-converting enzyme inhibitor (ACEI) group as potential drugs. ACEIs are among the leading drugs used in the treatment of hypertension in the world. The chemical modifications of the tested substances applied concerned the places most susceptible to degradation. The presented work analyzed the compatibility of new derivatives with selected excipients used in pharmacy. Methods: Thermogravimetric (TGA) and differential thermal analyses (c-DTA) were used as the main methods. In addition, non-thermal methods such as colorimetry analysis, Fourier-transform infrared (FTIR) and UV spectroscopy were used. Results: Based on the conducted studies, it can be concluded that the incompatibility of IND-1 with glucose anhydrous and lactose monohydrate occurs only when the mixture is stored at higher temperatures. For the remaining IND-1 and IND-2 mixtures with excipients, compatibility was demonstrated. Conclusions: The obtained results confirmed the usefulness of the applied thermal analyses (TGA and c-DTA) for assessing the compatibility of the tested potential drugs with excipients. However, in the case of incompatibility reactions of substances occurring under the influence of elevated temperatures, such as the Maillard reaction, it is necessary to use non-thermal methods to obtain the right result.

ACE inhibitory effect and saltiness-enhancing properties of chicken-derived umami peptides: Digestive stability, inhibition kinetics, multiple ligand docking and central composite design

Angiotensin-I-converting enzyme (ACE) inhibitory activity and saltiness-enhancing properties of chicken-derived umami peptides were investigated. DGGRYY and NEFGYSNR were screened and the IC50 values were 28.71 μM and 283.24 μM, indicating their potential as novel ACE inhibitors. DGGRYY and NEFGYSNR have good pH and thermal stability. After gastrointestinal digestion, the ACE-inhibitory activity of DGGRYY retained about 53 %, whereas NEFGYSNR retained about 57 %. The inhibition pattern of both peptides was determined to be uncompetitive, consisting with the result of multiple ligand docking that the binding sites were outside the ACE active pocket. Trp59, Tyr62, Asp121, Arg124, and Ser516 were the key binding sites that contributed to the total binding energy. In addition, saltiness and palatability models were established according to sensory analysis and central composite design. In 0.1 % ~ 0.3 % NaCl solutions, the addition of DGGRYY and NEFGYSNR could enhance the salty intensity and compensate for the palatability loss caused by salt reduction.

From Sea to Lab: Angiotensin I-Converting Enzyme Inhibition by Marine Peptides-Mechanisms and Applications.

To reveal potent ACE inhibitors, researchers screen various bioactive peptides from several sources, and more attention has been given to aquatic sources. This review summarizes the recent research achievements on marine peptides with ACE-inhibitory action and application. Marine peptides are considered excellent bioactives due to their large structural diversity and unusual bioactivities. The mechanisms by which these marine peptides inhibit ACE include competitive binding to ACEs' active site, interfering with ACE conformational changes, and avoiding the identification of substrates. The unique 3D attributes of marine peptides confer inhibition advantages toward ACE activity. Because IC50 values of marine peptides' interaction with ACE are low, structure-based research assumes that the interaction between ACE and peptides increased the therapeutic application. Numerous studies on marine peptides focused on the sustainable extraction of ACE-inhibitory peptides produced from several fish, mollusks, algae, and sponges. Meanwhile, their potential applications and medical benefits are worth investigating and considering. Due to these peptides exhibiting antioxidant, antihypertensive, and even antimicrobial properties simultaneously, their therapeutic potential for cardiovascular disease and other illnesses only increases. In addition, as marine peptides show better pharmacological benefits, they have increased absorption rates and low toxicity and could perhaps be modified for better stability and bioefficacy. Biotechnological advances in peptide synthesis and formulation have greatly facilitated the generation of peptide-based ACE inhibitors from marine sources, which subsequently offer new treatment models. This article gives a complete assessment of the present state of knowledge about marine organism peptides as ACE inhibitors. In addition, it emphasizes the relevance of additional investigation into their mechanisms of action, the optimization of manufacturing processes, and assessment in in vivo, preclinical, and clinical settings, underlining the urgency and value of this study. Using marine peptides for ACE inhibition not only broadens the repertory of bioactive compounds but also shows promise for tackling the global health burden caused by cardiovascular diseases.

Novel Bioactive Peptides from Red Bigeye (Priacanthus macracanthus) Flesh Protein

Red bigeye (Priacanthus macracanthus) is a common fish species in Malaysia. This study reported an in silico assessment of the main proteins in red bigeye flesh as precursors for bioactive peptides. Six major proteins were chosen as precursors from the proteomic profiles of red bigeye proteins. Analyses using the BIOPEP-UWM database found that Protein number 4 gave the highest total number of bioactive peptides (5052 peptides), with dominant bioactivity in angiotensin-I-converting enzyme (ACE) inhibition (1571 peptides) and dipeptidyl peptidase-IV (DPP-IV) inhibition (2238 peptides). The ACE inhibitors had a frequency of bioactive fragment occurrences (A) of 0.4098, while the DPP-IV inhibitors gave a frequency of 0.5805. In silico proteolysis using BIOPEP-UWM found that pepsin (pH > 2) was the most promising proteinase in releasing a high number of DPP-IV and ACE inhibitory peptides. A novel peptide with significant potential was identified as QYKF. This study shows that red bigeye is a potential source of antihypertensive and antidiabetic peptides.

Computational Study of Molecular Mechanism for the Involvement of Human Serum Albumin in the Renin–Angiotensin–Aldosterone System

Human serum albumin (HSA) is an endogenous inhibitor of angiotensin I-converting enzyme (ACE) and, thus, plays a key role in the renin–angiotensin–aldosterone system (RAAS). However, little is known about the mechanism of interaction between these proteins, and the structure of the HSA–ACE complex has not yet been obtained experimentally. The purpose of the presented work is to apply computer modeling methods to study the interaction of HSA with ACE in order to obtain preliminary details about the mechanism of their interaction. Ten possible HSA–ACE complexes were obtained by the procedure of macromolecular docking. Based on the number of steric and polar contacts between the proteins, three leading complexes were selected, the stabilities of which were then tested by molecular dynamics (MD) simulation. Based on the results of MD simulation, the two most probable conformations of the HSA–ACE complex were selected. The analysis of these conformations revealed that the processes of oxidation of the thiol group of Cys34 of HSA and the binding of albumin to ACE can reciprocally affect each other. Known point mutations in the albumin molecules Glu82Lys, Arg114Gly, Glu505Lys, Glu565Lys and Lys573Glu can also affect the interaction with ACE. According to the result of MD simulation, the known ACE mutations, albeit associated with various diseases, do not affect the HSA–ACE interaction. A comparative analysis was performed of the resulting HSA–ACE complexes with those obtained by AlphaFold 3 as well as with the crystal structure of the HSA and the neonatal Fc receptor (FcRn) complex. It was found that domains DI and DIII of albumin are involved in binding both ACE and FcRn. The obtained results of molecular modeling outline the direction for further study of the mechanisms of HSA–ACE interaction in vitro. Information about these mechanisms will help in the design and improvement of pharmacotherapy aimed at modulation of the physiological activity of ACE.

Comparative efficacy of amino acid availability and peptidomic analysis of alternative proteins from different sources under dynamic in vitro protein digestion

The increasing global demand for animal protein highlights the critical necessity of exploring alternative protein sources. Accessing the nutritional characteristics of emerging alternative proteins is vital for food processing and consumer acceptance. This study investigated the amino acid availability and peptidomics profiles of plant- (soy), fungal- (filamentous fungus Fusarium venenatum), microalgae- (Nannochloropsis oculata), and insect-based (black soldier fly) proteins using an advanced dynamic in vitro digestion system, with whey protein as a reference. After gastric digestion, soy and mycelial proteins, despite displaying distinct microstructures, exhibited slightly higher protein digestibility levels of 28.79% and 26.36%, respectively, compared to whey protein (22.39%). However, following small intestinal digestion, whey protein (61.31%) significantly outperformed alternative proteins. Mycelial protein (43.71%) exhibited digestibility similar to soy protein (46.12%), markedly surpassing both microalgae protein (33.35%) and insect protein (26.58%). Notably, insect protein achieved an amino acid availability nearly approaching that of whey protein, underscoring its substantial proteolysis capability. Furthermore, microalgae protein produced the highest percentage and number of bioactive peptides under simulated digestion, suggesting potential health benefits such as angiotensin I-converting enzyme (ACE) and dipeptidyl peptidase-IV (DPP-IV) inhibitor activities, which could mitigate the risk of hypertension and Type 2 diabetes. Alternative proteins from different sources demonstrate diverse digestive mechanisms and proteolysis profiles, thereby bolstering their potential applications as nutritious food ingredients in the future.

Preparation and stability of angiotensin-I-converting enzyme (ACE) inhibitory peptides from protein hydrolysate of Wuyi rock tea residues

ABSTRACT Wuyi rock tea residues, generated after brewing or aroma extraction, are rich in nutrients. This study aimed to prepare ACE inhibitory peptides from the protein hydrolysate of Wuyi rock tea residues and investigate their stability. The optimal proteolysis conditions for neutral protease were optimized as: a substrate concentration of 2% (w/v), pH 7.0, hydrolysis temperature of 45°C, enzymatic digestion time of 3 h, and enzyme dosage of 6800 U/g. Under these conditions, the ACE inhibition rate of protein hydrolysate of Wuyi rock tea residues reached 70.47 ± 0.29% at a concentration of 0.5 mg/mL. Additionally, the prepared ACE inhibitory peptides demonstrated excellent stability against acid, base, heat, and certain metal ions. These findings suggest that the proteins extracted from Wuyi rock tea residues can serve as a promising source to produce highly active ACE inhibitory peptides. These peptides could be utilized in the development of nutraceuticals, functional foods, and pharmaceuticals.

Amino Acid Composition, Antioxidant and Antihypertensive Activity in Extracts from Mexican Añejo Cheese.

Authentic Mexican cheeses have potential health benefits, although there are few studies on their bioactive components. In this study, we analysed soluble extracts from añejo cheese from Zacazonapan (Mexico), obtained from two dairies (A and B) that used milk from cows of different breeds and differed in processing. The soluble extracts of Zacazonapan añejo cheese during ripening (0, 30, 95 and 180 days) were used to determine proximate composition, amino acid composition, peptide profile, molecular mass profile, antioxidant and antihypertensive activities. The molecular mass of the released protein fragments ranged from 0.10 to 22.43 kDa. During ripening, amino acids such as Pro, His, Tyr, Trp, Met, Cys, Ala, Gly, Leu and Val were present, which are associated with antioxidant activity. The inhibition of β-carotene bleaching was below 50 % at all ripening times. A significant difference between the cheese samples was observed only after 180 days. Amino acids associated with angiotensin-I converting enzyme (ACE-I) inhibition were found in the extracts (Trp, Phe, Tyr, Pro, Lys and Arg). The highest activity was observed in cheese ripened for 180 days (IC50 of cheese A and B was 0.38 and 0.42 mg/mL, respectively). These results suggest that Zacazonapan añejo cheese is a potential source of antioxidant and antihypertensive peptides, which are influenced by the dairy factor (milk source and production technique) and ripening time. This is relevant as there are no reports of these bioactivities in this type of cheese.

Peptidomics profiling and biological activities of grape pomace protein hydrolysates

Grape pomace protein isolate was hydrolysed by Alcalase, Flavourzyme and Protease either individually or in combination to produce hydrolysates with antihypertensive and antimicrobial properties. The degree of hydrolysis (DH) ranged between 22 and 52 % for Protease and Flavourzyme, respectively. Among all treatments, hydrolysates prepared using Flavourzyme exhibited the highest angiotensin-converting enzyme inhibitory (ACEi) activity, with an IC50 value of 91 μg/mL. The peptidomics analysis revealed that the peptides identified in Flavourzyme hydrolysate presented molecular features compatible with its bioactivity, like a high density of ACEi sequences per peptide. The hydrolysates were also able to inhibit the growth of Escherichia coli in a range between 9 and 54 % for Alcalase and Alcalase + Flavourzyme, respectively. Peptides in the most active hydrolysate evidenced a high occurrence of proline residues, which is a structural feature of some antimicrobial peptides.

Hypotensive effect of potent angiotensin-I-converting enzyme inhibitory peptides from corn gluten meal hydrolysate: Gastrointestinal digestion and transepithelial transportation modifications

The study examined the antihypertensive effect of peptides derived from pepsin-hydrolyzed corn gluten meal, namely KQLLGY and PPYPW, and their in silico gastrointestinal tract digested fragments, KQL and PPY, respectively. KQLLGY and PPYPW showed higher angiotensin I-converting enzyme (ACE)-inhibitory activity and lower ACE inhibition constant (Ki) values when compared to KQL and PPY. Only KQL showed a mild antihypertensive effect in spontaneously hypertensive rats with −7.83 and − 5.71 mmHg systolic and diastolic blood pressure values, respectively, after 8 h oral administration. During passage through Caco-2 cells, KQL was further degraded to QL, which had reduced ACE inhibitory activity. In addition, molecular dynamics revealed that the QL-ACE complex was less stable compared to the KQL-ACE. This study reveals that structural transformation during peptide permeation plays a vital role in attenuating antihypertensive effect of the ACE inhibitor peptide.

Chemical characterization and angiotensin-I converting enzyme inhibitory activity of Indonesian stinky beans

The chemical composition of four Indonesian stinky beans has been explored. Those bean are Petai (Parkia speciosa), Lamtoro Gung (Leucaena leucochepala ssp. Glabrata (Rose) S. Zarate), Jengkol (Pithecellobium jiringa) and Kabau (Archidendron bubalinum). This exploration belongs to the local food utilization research theme of functional food sources. Those beans have a unique flavour and usually lead to foul stools, sweat, urine or mouth odour. Their intense flavour may be due to the content of amino acids. High hydrophobic and negative charge hydrophilic amino acids are crucial in preventing hypertension through inhibition of angiotensin I-converting enzyme (ACE) activity. This study evaluated the chemical properties of beans and its angiotensin I-converting enzyme inhibitory (ACE-I) peptides. The amino acid profile was determined as preliminary data to ensure the content of hydrophobic and negative charge hydrophilic amino acids. Their ability to inhibit ACE was studied to represent an antihypertensive effect. In vitro gastrointestinal digestion was applied to obtain more small molecular peptides and evaluate their ACE-I activity after digestion. Petai has the highest glutamic acid (20.90 g/100 g protein d.b.), lysine (13.31 g/100 g protein d.b.), arginine (11.76 g/100 g protein d.b.), leucine (10.98 g/100 g protein d.b.), and aspartic acid (10.72 g/100 g protein d.b.). Fresh Jengkol has the highest ACE-I activity (67.59%). Subsequential digestion by pepsin and pancreatin improves the ACE-I activity, and Kabau had the highest (79.87%). Based on the results, Indonesian stinky beans can prevent hypertension by inhibiting ACE activity and being used as a protein source alternative

Antioxidant activity and inhibitory effects on angiotensin I-converting enzyme and α-glucosidase of trans-p-coumaroyl-secologanoside (comselogoside) and its inclusion complex with β-cyclodextrin. Bioaccessibility during simulated in vitro gastrointestinal digestion.

This study explored the impact of complexing comselogoside (COM) with β-cyclodextrin (β-CD) on antioxidant capacity and investigated its in vitro inhibitory effects against α-glucosidase and angiotensin I-converting enzyme (ACE). The COM: β-CD complex in three molar ratios (1:2, 1:1, and 2:1) showed significantly higher antioxidant activity compared to free COM, assessed by DPPH and ferric reducing power assays. COM exhibited weak to moderate α-glucosidase inhibition (IC50 1221 μM) and notable ACE inhibition (IC50 119.4 μM). Encapsulation improved ACE inhibition notably for the 1:2 and 2:1 M ratios. The cleavage of secoiridoid moiety of COM by β-glucosidase further enhanced ACE inhibition from IC50 of 63.91 to 41.75 μg/mL in the hydrolysed mixture. In vitro gastrointestinal digestion revealed 34–40% bioaccessibility of COM and its β-CD complex. This study demonstrates the potential of encapsulated COM as a functional food or supplement for preventing and treating diabetes, hypertension, and oxidative stress-related diseases.

A novel ACE inhibitory peptide from Douchi hydrolysate: Stability, inhibition mechanism, and antihypertensive potential in spontaneously hypertensive rats

Angiotensin I-converting enzyme (ACE) regulates blood pressure through the renin-angiotensin system. Douchi, a traditional fermented soybean condiment, may have antihypertensive effects, but research on ACE inhibitory peptides from Douchi hydrolysates is limited. We hypothesized that enzymatic treatment could enhance ACE inhibitory peptide diversity and efficacy. We tested ten single enzymes and four combinations, finding pepsin-trypsin-chymotrypsin most effective. Hydrolysates were purified using Sephadex G-15 and reversed-phase HPLC, and peptides were identified via LC-MS/MS. Five peptides (LF, VVF, VGAW, GLFG, NGK) were identified, with VGAW as the most potent ACE inhibitor (IC50 46.6 ± 5.2 μM) showing excellent thermal and pH stability. Lineweaver-Burk plots confirmed competitive inhibition, and molecular docking revealed eight hydrogen bonds between VGAW and ACE. In hypertensive rats, VGAW significantly reduced blood pressure at 12.5, 25, and 50 mg/kg. These findings highlight Douchi as a source of ACE inhibitory peptides and suggest VGAW as a promising functional food ingredient.

Identification and molecular mechanism of novel ACE inhibitory peptides from broccoli protein

Many natural angiotensin-converting enzyme inhibitory (ACEI) peptides have been widely studied and used to prevent and control hypertension. In this study, peptideomics and 3D-QSAR models combined with experimental verification were used to rapidly screen ACEI peptides in broccoli protein hydrolysates, followed by molecular docking and intracellular antihypertensive activity analysis. The results showed that two novel peptides FVLPLR and LPWYR were obtained, and their IC50 values for inhibiting ACE activity in vitro were 3.06 μM and 19.05 μM, respectively. Molecular docking results showed that FVLPLR and LPWYR bind to ACE through hydrogen bonding, electrostatic interaction, and hydrophobic interaction. Both peptides can promote HUVEC cells to produce vasodilator factor NO. These results indicated that broccoli protein could be used as an excellent source of ACE inhibitors.

In Silico Screening of Bioactive Peptides in Stout Beer and Analysis of ACE Inhibitory Activity.

Stout beer was selected as the research object to screen angiotensin-converting enzyme (ACE) inhibitory peptides. The peptide sequences of stout beer were identified using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry with de novo, and 41 peptides were identified with high confidence. Peptide Ranker was used to score the biological activity and six peptides with a score ≥ 0.5 were screened to predict their potential ACE inhibitory (ACEI) activity. The toxicity, hydrophilicity, absorption, and excretion of these peptides were predicted. In addition, molecular docking between the peptides and ACE revealed a significant property of the peptide DLGGFFGFQR. Furthermore, molecular docking conformation and molecular dynamics simulation revealed that DLGGFFGFQR could be tightly bound to ACE through hydrogen bonding and hydrophobic interaction. Lastly, the ACEI activity of DLGGFFGFQR was confirmed using in vitro evaluation and the IC50 value was determined to be 24.45 μM.

Angiotensin-I converting enzyme (ACE) inhibitory bioaccessible peptides obtained from protein extracts of Macrocystis pyrifera and Chondracanthus chamissoi seaweeds

Hypertension is a paramount chronic health concern, underscoring the critical need for preventive measures in public health. In recent years, research has discovered natural anti-hypertensive agents, including those derived from macroalgae. This study focuses on enzymatically hydrolyzing protein extracts from Macrocystis pyrifera and Chondracanthus chamissoi seaweeds to yield angiotensin I-converting enzyme (ACE) inhibitory peptides, potentially applicable in both food and bioactive products. ACE inhibitory activity was evaluated for enzymatic hydrolysates generated using bromelain, papain, and alcalase. Notably, hydrolysates produced using alcalase demonstrated the highest effect, yielding 74 % ACE inhibition for M. pyrifera and 58 % for C. chamissoi protein extracts. Optimization efforts focused on hydrolysis conditions, varying hydrolysis time and substrate-to-enzyme ratio, resulting in peak ACE inhibition of 79.9 % for M. pyrifera (5.3 h, 12.7 S:E ratio) and 70.3 % for C. chamissoi (6 h, 10 S:E ratio).Further analysis explored the relationship between molecular size separation and ACE inhibitory activity in algae hydrolysates. Fractionation via ultrafiltration revealed that fractions below 3 kDa exhibited the highest ACE inhibitory potency. Additionally, in vitro digestion studies employing pepsin and pancreatin treatments demonstrated the bioaccessibility of the seaweed-derived bioactive peptides, with maintained or enhanced bioactivity post-digestion. These findings underscore the potential of protease hydrolysates from M. pyrifera and C. chamissoi as sources of ACE inhibitory activity. Consequently, they present an exciting natural source of functional ingredients or nutraceuticals for hypertension management, with the benefits of easy implementation, profitability, and sustainability in their production process.

Releasing angiotensin I‐converting enzyme inhibitory (ACE‐I) peptides by Yamadazyma spp. in non‐fat milk

SummaryThe objectives of this study were to analyse the impact of both temperature and different isolates on microbial protease production ability and to examine the hypertensive effect of bioactive peptides (BAPs) that inhibit the angiotensin I‐converting enzyme released by fermentation of non‐fat milk. First, the ability of several Yamadazyma spp. isolates, which were previously isolated and identified from several sources, was screened in terms of the production of proteolytic enzymes at 15 and 25 °C. The effect of temperature on proteolysis activity of selected isolates was considerable, and incubation at 25 °C was favourable for protease production. Besides, combinations of three different isolates showed remarkable proteolytic activity during the incubation periods of 24, 48 and 72 h. The highest angiotensin I‐converting enzyme inhibitory (ACE‐I) activity was detected for the combination Yamadazyma spp. BO10 and B514‐1, with an inhibition of 92.5%. The partial purification of peptides by ultrafiltration (cut‐off 10 kDa) has no crucial impact on ACE‐I activity, and further purification might improve their effectiveness. The implications of fermentation with co‐culture may have symbiotic potential to increase the antihypertensive effect of the product. Therefore, these results suggest that Yamadazyma spp. may be used to produce functional products or bioactive peptides presenting health‐promoting attributes.

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.