ACE-inhibitory Activity Research Articles

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.

Functional Peptides from Yak Milk Casein: Biological Activities and Structural Characteristics.

The average content of casein in yak milk is 40.2 g/L. Casein can be degraded by enzymatic digestion or food processing to produce abundant degradation peptides. International researchers have studied the degradation peptides of yak milk casein by using multiple techniques and methods, such as in vitro activity tests, cellular experiments, proteomics, bioinformatics, etc., and found that the degradation peptides have a wide range of functional activities that are beneficial to the human body, such as angiotensin-converting enzyme (ACE) inhibitory, antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer, and immunomodulatory activities, etc., and it has been proved that the types and strengths of functional activities are closely related to the structural characteristics of the peptides. This paper describes the characteristics of yak milk proteins, the functional activities, and mechanism of action of degraded peptides. Based on the types of functional activities of yak milk casein degradation peptides, we classified and elucidated the effects of structural factors, such as peptide molecular weight, peptide length, amino acid sequence, physicochemical properties, electrical charge, hydrophobicity, spatial conformation, chain length, and the type of enzyme on these activities. It reveals the great potential of yak milk casein degradation peptides as functional active peptide resources and as auxiliary treatments for diseases. It also provides important insights for analyzing yak casein degradation peptide activity and exploring high-value utilization.

Improving natto quality through Co-fermentation of functionally complementary Bacillus and Lactiplantibacillus species

Natto, a nutritious fermented soybean product, is known for its health benefits. Modern production methods use Bacillus subtilis as the starter culture to ensure consistent quality. However, this method overlooks the potential positive effects of other microbial species present in traditionally, naturally fermented natto. This study explored the effects of ARTP-induced mutants of B. subtilis var. natto and several strains of lactic acid bacteria (LAB) on natto quality. The results showed that these two types of bacteria have complementary roles in fermentation. B. subtilis var. natto, with enhanced extracellular protease activity, promotes the hydrolysis of soy protein and enhances the product's ACE inhibitory and fibrinolytic activities. Meanwhile, two strains of Lactiplantibacillus plantarum reduced the content of total volatile basic nitrogen (TVB-N) while increasing the content of folic acid in the final product. In addition, B. subtilis var. natto and LAB produce different profiles of volatile compounds (VOCs). Subsequently, B. subtilis var. natto and Lpb. plantarum were used to co-ferment natto in different ratios. The results showed that the two types of bacteria could co-colonize and enhance fermentation quality through their respective strengths. Specifically, Lpb. plantarum strains co-metabolized with B. subtilis var. natto to elevate the content of pyrazines, characteristic VOCs in natto. The optimal quality of natto was achieved when Lpb. plantarum HIS6, Lpb. plantarum LP3 and B. subtilis var. natto Y15-11 were combined in a 2:1:2 ratio. This study not only identified effective combinations of starter cultures with complementary benefits but also elucidated the metabolic pathways of key volatile compounds. Our findings also provide technical insights for improving natto quality, enhancing consumer acceptance, and supporting industrial production.

Presence of Modified Peptides with High Bioavailability and Angiotensin-Converting Enzyme Inhibitory Activity in Japanese Fermented Soybean Paste (Miso).

Not only free amino acids and normal short-chain peptides but also modified amino acids, such as N-acetyl- and N-formyl amino acids, monoamines, polyamines, and modified peptides, such as isomerized aspartyl peptides, pyroglutamyl peptides, and diketopiperazines, were identified in Japanese fermented soy paste (miso) prepared using different fungal starters, rice, barley, and soybean-koji. One hour after oral administration of water extract of soybean-koji miso to rats, the modified peptides increased significantly in the lumen upon the ingestion, while the normal peptides did not. In the blood from the portal vein and abdominal vena cava, 17 and 15 diketopiperazines, 16 and 12 isomerized aspartyl peptides, and 2 and 1 pyroglutamyl peptides significantly increased to approximately 10-400 nM, respectively. The modified peptides, which increased in rat blood, showed angiotensin-converting enzyme (ACE) inhibitory activity in a dose-dependent manner, indicating multiple ACE inhibitory peptides with high bioavailability in miso. Among them, l-β-Asp-Pro showed the highest ACE inhibitory activity (IC50 4.8 μM).

Combined Peptidomics and Metabolomics Analyses to Characterize the Digestion Properties and Activity of Stropharia rugosoannulata Protein-Peptide-Based Materials.

Protein-peptide-based materials typically possess high nutritional value and various physiological regulatory activities. This study evaluated the digestion, metabolism, and activity of Stropharia rugosoannulata protein-peptide-based materials. After the S. rugosoannulata protein-peptide-based materials were digested (simulated) orally, in the stomach, and in the intestines, the proportions of >10,000 Da, 5000~10,000 Da, and <180 Da in the digestion products increased, and the peptide content was maintained at more than 120 mg/g dry weight. The digestion products of eight test groups with different oral-gastrointestinal digestion-level settings all had suitable ACE inhibitory activity (IC50 range 0.004~0.096 mg/mL). The main metabolite groups were lipid-like molecules, fatty acids, carboxylic acids, their derivatives, amino acids, peptides, and analogs. Bile and glycosylated amino acids were the main compounds that caused differences between groups. KEGG pathways enriched in differentially expressed metabolites included eight significantly upregulated pathways, including valine, leucine, and isoleucine biosynthesis, etc., and six significantly downregulated pathways, including the citric acid cycle (tricarboxylic acid cycle), etc. The arginine and proline metabolism pathways and the aminoacyl-tRNA biosynthesis pathways were upregulation and downregulation pathways that enriched multiple differentially expressed metabolites. Twenty-six metabolites, including bile acids, total bile acids, and the essential amino acids L-isoleucine and L-leucine, were differentially expressed metabolite markers of the protein-peptide-based material oral-gastrointestinal digestion products.

ESSENTIAL OIL CONTENTS AND BIOLOGICAL ACTIVITIES OF THYMUS CANOVIRIDIS JALAS AND THYMUS SIPYLEUS BOISS.

Objective: Members of the Lamiaceae family are considered to be major sources of bioactive therapeutic agents. Many of them are important medicinal and aromatic plants used in traditional and modern medicine and in the food, cosmetic and pharmaceutical industries. The aim of this study was to investigate in detail the biological activities and chemical composition of the essential oils of Thymus canoviridis Jalas and Thymus sipyleus Boiss. species belonging to the genus Thymus, one of the most important genera of the Lamiaceae family. Material and Method: The essential oil content of the species was determined by GC-MS. Antioxidant activities of the essential oils were determined using lipid peroxidation, DPPH free radical, ABTS cation radical and CUPRAC methods. In addition, cytotoxic activities against breast cancer (MCF-7) and colon cancer (HT-29) cell lines and anticholinesterase (against AChE and BChE enzymes), urease, tyrosinase, elastase, collagenase and angiotensin converting enzyme inhibition activities were determined. Result and Discussion: When the essential oil composition of T. sipyleus was analyzed, the major compounds were 1,8-cineole (eucalyptol) (18.16%), camphor (15.08%) and endo-borneol (11.63%), while T. canoviridis was found to be rich in carvacrol (72.88%). T. canoviridis showed high antioxidant activity in lipid peroxidation (IC50: 45.72±0.12 μg/ml), ABTS (IC50: 6.12±0.03 μg/ml) and CUPRAC (IC50: 5.31±0.01 μg/ml) methods. The selectivities of T. canoviridis and T. sipyleus species against MCF-7 cell line were 4.39 and 6.81, respectively. In the enzyme inhibition studies, both Thymus species showed moderate inhibition activity against BChE enzyme (Inhibition%: 57.88±1.14, 39.21±0.89, respectively). In addition, T. sipyleus showed moderate inhibition of elastase enzyme (Inhibition%: 25.33±0.79). When the results are evaluated in general, it can be said that T. canoviridis essential oil with its rich carvacrol content and high cytotoxic and antioxidant activity can be preferred as a safer and natural option instead of synthetic preservatives in food, pharmaceutical and cosmetic industries to extend shelf life and ensure food safety.

Bioactive, Pro-Apoptotic-Angiotensin Converting Enzyme Inhibitor Effects and Properties of Ultrasound-Treated Traditional Poppy Vinegar Using the Response Surface Methodology Model.

Poppy vinegar with functional properties is a fermented product. This study evaluated traditionally produced poppy vinegar. The study was conducted on poppy vinegar to determine the maximum increase in angiotensin converting enzyme (ACE) inhibitory activity %, total phenolic content (TPC), and radical scavenging activity (DPPH) of the vinegar at different combinations of ultrasound treatment duration (2-14 min) and amplitude (40-100%). The optimal parameters obtained using the response surface methodologies (RSM) were the duration of the ultrasound of 5.5 min and the amplitude of the ultrasound at 57%. When the DPPH values, ACE inhibition %, and TPC and DPPH values obtained with the RSM model were compared with the experimental values, the difference was 9.80, 3.0, and 4.6%, respectively, showing good agreement between actual and predicted values. The higher ultrasound intensities and longer treatment times had a significant effect on antioxidant activity. Poppy vinegar samples significantly induced the apoptosis of lung cancer cells, particularly those stored for 6 and 12 months. The amounts of protocatechuic acid, gallic acid, neohesperidin, hydroxybenzoic acid, resveratrol, rutin, trans-cinnamic acid, quercetin, and flavon in poppy vinegar were determined, which decreased significantly as storage time increased. TPC and TFC were determined to be 90.39 mg of GAE/100 mL and 29.86 mg of TEAC/mL, respectively, and there was no significant change in these bioactive compounds after 6 months of storage. The highest value of ACE inhibitory activity was found at the beginning of the storage period. The present study was the first study to examine the bioactive components, ACE inhibition activity, pro-apoptotic activities, and phenolic composition of traditionally produced ultrasound-treated poppy vinegar during storage. The control of production parameters and the design of ideal poppy vinegar fermentation processes could benefit from this research.

Yogurt fortified with various protein hydrolysates: Texture and functional properties

This work evaluated the impact of incorporating 1% of commercial protein hydrolysates [rice protein hydrolysate (RPH), pea protein hydrolysate (PPH), and casein hydrolysate (CH)] on the functional, microstructure, and texture properties of set yogurt. Yogurt prepared with RPH exhibited the highest viability number of Streptococcus thermophilus. The addition of three hydrolysate types to yogurt revealed significant increases in the antioxidant and ACE-inhibitory activities, where the highest values were noted for the yogurt prepared with RPH. RPH exhibited no differences in texture properties (firmness, consistency, and cohesiveness) to control yogurt. These results were confirmed by scanning electron microscope examination. RPH and control yogurts showed compacted and dense structures accompanied by small pores, whereas CH and PPH yogurt structures were characterized by coarse networks with large voids. Furthermore, there was no significant impact of adding protein hydrolysates on the overall acceptability of yogurt as indicated by a sensory panel.

Ultrasonication assisted enzymatic hydrolysis for generation of pulses protein hydrolysate having antioxidant and ACE-inhibitory activity

The main objective of this work was to investigate the impact of ultrasonication assisted enzymatic treatment on the physicochemical and bioactive properties of broad bean (BBP), lentil bean (LBP), and mung bean (MBP) protein isolates. The protein was extracted using alkaline acid precipitation method, ultrasonicated at a frequency of 20 kHz, temperature 20–30 °C and then hydrolysed using alcalase enzyme (1 % w/w, pH 8.5, 30 min, 55 οC). The generated hydrolysates were characterized by degree of hydrolysis (DH), SDS, FTIR, surface hydrophobicity, amino acid composition, antioxidant and antihypertensive properties. Results showed that the degree of hydrolysis was found to increase in ultrasonicated protein hydrolysate (18.9 to 40.71 %) in comparison to non- ultrasonicated protein hydrolysate (11 to 16.3 %). SDS-PAGE results showed significant changes in protein molecular weight profiles (100–11kDa) in comparison to their natives. However, no substantial change was found in ultrasonicated and non-ultrasonicated protein hydrolysates. The FTIR spectrum showed structural alterations in ultrasonicated and non-ultrasonicated protein hydrolysates, suggesting modifications in secondary structure such as amide A, amide I and amide II regions. The essential amino acid content varied in the range of 60.09 mg/g to 73.77 mg/g and 28.73 to 50.26 mg/g in case of ultrasonicated and non-ultrasonicated protein hydrolysates, and non-essential content varied in the range of 49.42 to 65.93 mg/g and 43.12 to 47.12 mg/g. Both antioxidant and antihypertensive activities were found to increase significantly in ultrasonicated and non-ultrasonicated protein hydrolysates in comparison to their native counterparts, highlighting their potential as functional ingredients for management of hypertension. It was concluded that ultrasonication assisted enzymatic hydrolysis is an efficient approach for production of bioactive pulse protein hydrolysates with enhanced nutracutical properties, thus offering promising avenues for their utilization in the food industry and beyond.

Evaluation of In Vitro Antihypertensive and Anti-Inflammatory Properties of Dairy By-Products

Sweet whey (SW) and yogurt acid whey (YAW) are dairy by-products of the cheese-making process and Greek-style yogurt production, respectively. Both of them are considered pollutants with huge volumes of SW and YAW produced due to the growing demand for dairy products worldwide. Moreover, whey-derived peptides, resulting from fermentation as well as from further hydrolysis during digestion, have been associated with various biological activities. In the present study, the angiotensin-converting enzyme (ACE)-inhibitory activity of 48 SW samples and 33 YAW samples from bovine, ovine, caprine, and ovine/caprine milk obtained were evaluated. Additionally, the SW and YAW digestates and two of their fractions (smaller than 10 kDa, SW-D-P10 and YAW-D-P10, and smaller than 3 kDa, SW-D-P3 and YAW-D-P3), which were obtained after in vitro digestion and subsequent ultrafiltration, were also subjected to evaluation. Our data indicated that the D-P10 and D-P3 fractions exhibited higher ACE-inhibitory activity compared to the corresponding values before digestion. The ACE-inhibitory capacity after in vitro digestion was higher for the ovine SW samples compared to their bovine and caprine counterparts. The effect of the D-P3 fraction on the inhibition of nitric oxide (NO) production and the expression of a selected panel of immune-response-related genes in LPS-stimulated RAW 264.7 macrophages was also evaluated. Fractions from both dairy by-products inhibited NO production in LPS-stimulated RAW 264.7 cells. Especially, ovine SW-D-P3 showed a strong NO inhibitory activity and suppressed inducible nitric oxide synthase (Nos2) mRNA levels. However, YAW-D-P3 could not trigger neither the gene expression of inflammatory macrophage mediators Nos2 and cyclooxygenase-2 (Ptgs2) nor tumor necrosis factor-α (Tnf) and interleukin 6 (Il6) in LPS-stimulated murine macrophages regardless of animal origin. These findings suggest that in vitro digestion could enhance the production of ACE-inhibitory peptides in both dairy by-products, while SW from ovine origin displays higher potential as an anti-inflammatory agent, effectively preventing excessive NO production.

Biological activities, Peptidomics and in silico analysis of low-fat Cheddar cheese after in vitro digestion: Impact of blending camel and bovine Milk

Cheesemaking with camel milk (CM) presents unique challenges and additional health benefits. This study involved preparing low-fat Cheddar cheese (LFCC) by blending bovine milk (BM) with varying levels of CM. Control cheese was made exclusively with BM. After 180 days of ripening, LFCC samples underwent in vitro digestion to determine antioxidant capacities, α-amylase and α-glucosidase inhibition, and angiotensin-converting enzyme inhibition. The peptide profile of LFCC treatments was analyzed using liquid chromatography-quadrupole-time of flight-mass spectrometry. Antioxidant and biological activities were influenced by BM-CM blends and digestion. At days 120 and 180, the number of αs1-casein-derived peptides increased in all samples except for LFCC made with 15% CM. Generally, 88 peptides exhibited ACE inhibition activity after 120 days of ripening, increasing to 114 by day 180. These findings suggest that ripening time positively affects the health-promoting aspects of functional cheese products.

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

Production of an Ice Cream Base with Added Lacticaseibacillus rhamnosus GG and Aguamiel Syrup: Probiotic Viability and Antihypertensive Capacity

Given the rising interest in functional foods for health benefits, this study aims to evaluate the antihypertensive activity of an ice cream base incorporating Lacticaseibacillus rhamnosus GG and aguamiel syrup. We assessed the probiotic viability and ACE inhibitory activity in ice cream enriched with aguamiel syrup compared to inulin. Several reports have highlighted the importance of consuming symbiotic dairy foods to modulate the intestinal microbiota and multiple pathophysiologies. Ice cream has a high worldwide consumption rate, so it is an alternative to incorporating probiotics and prebiotics. The probiotic was inoculated (109 CFU/mL) into an ice cream base enriched with aguamiel syrup and a control base with added inulin. The carbohydrate profiles in the aguamiel (used to produce the syrup) and the aguamiel syrup were obtained through HPLC. TNBS and SDS-PAGE analysis were used to determine the proteolytic action of the probiotic. Sucrose was the carbohydrate with the highest concentration in fresh aguamiel and aguamiel syrup. The probiotic remained viable for 14 days under refrigerated storage conditions, with the aguamiel syrup base showing superior protein hydrolysis (free amino groups 302.67 ± 2.29 µg/mL) and 65% ACE inhibition. Likewise, the pH remained unchanged throughout the refrigerated days. These results underscore the potential of aguamiel syrup as a prebiotic in functional dairy products.

Fermentation of Rice, Oat, and Wheat Flour by Pure Cultures of Common Starter Lactic Acid Bacteria: Growth Dynamics, Sensory Evaluation, and Functional Properties.

Recent consumer demand for non-dairy alternatives has forced many manufacturers to turn their attention to cereal-based non-alcoholic fermented products. In contrast to fermented dairy products, there is no defined and standardized starter culture for manufacturing cereal-based products. Since spontaneous fermentation is rarely suitable for large-scale commercial production, it is not surprising that manufacturers have started to adopt centuries-known dairy starters based on lactic acid bacteria (LABs) for the fermentation of cereals. However, little is known about the fermentation processes of cereals with these starters. In this study, we combined various analytical tools in order to understand how the most common starter cultures of LABs affect the most common types of cereals during fermentation. Specifically, 3% suspensions of rice, oat, and wheat flour were fermented by the pure cultures of 16 LAB strains belonging to five LAB species-Lacticaseibacillus paracasei, Lactobacillus delbrueckii, Lactobacillus helveticus, Streptococcus thermophilus, and Lactococcus lactis. The fermentation process was described in terms of culture growth and changes in the pH, reducing sugars, starch, free proteins, and free phenolic compounds. The organoleptic and rheological features of the obtained fermented products were characterized, and their functional properties, such as their antioxidant capacity and angiotensin-converting enzyme inhibitory activity, were determined.

Protein Hydrolysates from Salmon Heads and Cape Hake By-Products: Comparing Enzymatic Method with Subcritical Water Extraction on Bioactivity Properties.

Fish by-products can be converted into high-value-added products like fish protein hydrolysates (FPHs), which have high nutritional value and are rich in bioactive peptides with health benefits. This study aims to characterise FPHs derived from salmon heads (HPSs) and Cape hake trimmings (HPHs) using Alcalase for enzymatic hydrolysis and Subcritical Water Hydrolysis (SWH) as an alternative method. All hydrolysates demonstrated high protein content (70.4-88.7%), with the degree of hydrolysis (DH) ranging from 10.7 to 36.4%. The peptide profile of FPHs indicated the breakdown of proteins into small peptides. HPSs showed higher levels of glycine and proline, while HPHs had higher concentrations of glutamic acid, leucine, threonine, and phenylalanine. Similar elemental profiles were observed in both HPHs and HPSs, and the levels of Cd, Pb, and Hg were well below the legislated limits. Hydrolysates do not have a negative effect on cell metabolism and contribute to cell growth. HPSs and HPHs exhibited high 2,2'-azino-bis(3 ethylbenzthiazoline-6)-sulfonic acid (ABTS) radical scavenging activity, Cu2+ and Fe2+ chelating activities, and angiotensin-converting enzyme (ACE) inhibitory activity, with HPHs generally displaying higher activities. The α-amylase inhibition of both FPHs was relatively low. These results indicate that HPHs are a promising natural source of nutritional compounds and bioactive peptides, making them potential candidates for use as an ingredient in new food products or nutraceuticals. SWH at 250 °C is a viable alternative to enzymatic methods for producing FPHs from salmon heads with high antioxidant and chelating properties.

Identification, screening and molecular mechanisms of natural stable angiotensin-converting enzyme (ACE) inhibitory peptides from foxtail millet protein hydrolysates: a combined in silico and in vitro study.

The stability of bioactive peptides under various food processing conditions is the basis for their use in industrial manufacturing. This study aimed to identify natural ACE inhibitors with excellent stability and investigate their physicochemical properties and putative molecular mechanisms. Five novel ACE inhibitory peptides (QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ) were isolated and identified using RP-HPLC and Nano LC-MS/MS with foxtail millet protein hydrolysates as the raw material. These peptides are non-toxic and exhibit strong ACE inhibitory activity in vitro (IC50 values between 0.13 mg mL-1 and 0.56 mg mL-1). In addition to QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ have excellent human intestinal absorption. Compared to FPGVSPF and SPAQLLPF, the stable helical structure of LVPYRP and WYWPQ allows them to maintain high stability under conditions that mimic gastrointestinal digestion and various food processing (temperatures, pH, sucrose, NaCl, citric acid, sodium benzoate, Cu2+, Zn2+, K+, Mg2+, Ca2+). The results of molecular docking and molecular dynamics simulation suggest that LVPYRP has greater stability and binding capacity to ACE than WYWPQ. LVPYRP might attach to the active pockets (S1, S2, and S1') of ACE via hydrogen bonds and hydrophobic interactions, then compete with Zn2+ in ACE to demonstrate its ACE inhibitory activity. The binding of LVPYRP to ACE enhances the rearrangement of ACE's active structural domains, with electrostatic and polar solvation energy contributing the most energy to the binding. Our findings suggested that LVPYRP derived from foxtail millet protein hydrolysates has the potential to be incorporated into functional foods to provide antihypertensive benefits.

Production of bioactive peptides during yogurt fermentation, their extraction and functional characterization

This study aimed to evaluate the antioxidant, antibacterial, antidiabetic and angiotensin-converting enzyme (ACE)-inhibitory effects of different fractions of bioactive peptides produced as a result of milk fermentation with yogurt starters and probiotics. In addition to yogurt starters, milk was fermented separately and together with Lacticaseibacillus rhamnosus GG and L. paracasei, then passed through 5 and 10 kDa (kilodalton) filters. A significant difference was observed in the fermentation time between the samples. The antioxidant, antibacterial, antidiabetic and ACE-inhibitory activities of the bioactive peptides were significantly affected by the probiotic strains and the molecular weight of the peptide (p < 0.05). ≤5 kDa fractions of Lactobacillus delbrueckii subsp. bulgaricus + Streptococcus thermophilus + L. rhamnosus GG + L. paracasei had the highest antioxidant activity. The addition of L. rhamnosus GG and L. paracasei to yogurt starter significantly increased ɑ-amylase activity, ɑ-glucosidase activity and ACE inhibitor activity. All samples showed antibacterial activity to Escherichia coli, Staphylococcus aureus, and Salmonella Typhimurium microorganisms and the molecular weight of peptides and sample types were significantly exhibited in antibacterial activity (p < 0.05). Cytotoxic activity showed that bioactive peptides had cytotoxic effect against Caco-2 adenocarcinoma cell and the presence of probiotics increased the cytotoxic effect. The results of the study suggest that the use of L. rhamnosus GG and L. paracasei, together with yogurt starters, could improve the bioactive properties of peptides formed in dairy products.

Phytochemical Investigation of Carex praecox Schreb. and ACE-Inhibitory Activity of Oligomer Stilbenes of the Plant.

Phenolic compounds are the main special metabolites of Cyperaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of constituents from Carex praecox. Twenty-six compounds, including lignans, stilbenes, flavonoids, megastigmanes, chromenes, and phenylpropanoids, were identified from the methanol extract of the plant. Five of these compounds, namely, carexines A-E, are previously undescribed natural products. All compounds were isolated for the first time from C. praecox. The ACE-inhibitory activity of seven stilbenoid compounds was tested, and (-)-hopeaphenol proved to be the most active (IC50 7.7 ± 0.9 μM). The enzyme-kinetic studies revealed a mixed-type inhibition; therefore, domain-specific studies were also conducted. The in silico docking of (-)-hopeaphenol to the ACE affirmed some favorable interactions. In addition, the antiproliferative and antibacterial effects of some compounds were also evaluated.

Effects of anaerobic treatment on the non-volatile components and angiotensin-converting enzyme (ACE) inhibitory activity of purple-colored leaf tea

This study investigated the effect of anaerobic treatment on the non-volatile components and angiotensin-converting enzyme (ACE) inhibitory activity in purple-colored leaf tea. Results showed that after 8 h of anaerobic treatment, the γ-aminobutyric acid (GABA) content significantly increased from 0.02 mg/g to 1.72 mg/g (p < 0.05), while lactic acid content gradually rose from non-detectable levels to 3.56 mg/g. Notably, certain flavonols like quercetin and myricetin exhibited significant increments, whereas the total anthocyanins (1.01 mg/g) and epigallocatechin-3-(3''-O-methyl) gallate (13.47 mg/g) contents remained almost unchanged. Furthermore, the ACE inhibition rate of purple-colored leaf tea increased significantly from 42.16% to 49.20% (p < 0.05) at a concentration of 2 mg/mL. Moreover, galloylated catechins showed stronger ACE inhibitory activity than non-galloylated catechins in both in vitro ACE inhibitory activity and molecular docking analysis. These findings might contribute to the development of special purple-colored leaf tea products with potential therapy for hypertension.

Ile-Pro-Pro attenuates sympathetic activity and hypertension.

Isoleucine-proline-proline (Ile-Pro-Pro, IPP) is a natural food source tripeptide that inhibits angiotensin-converting enzyme (ACE) activity. The aim of this study was to determine the central and peripheral roles of IPP in attenuating sympathetic activity, oxidative stress and hypertension. Male Sprague-Dawley rats were subjected to sham-operated surgery (Sham) or two-kidney one-clip (2K1C) surgery to induce renovascular hypertension. Renal sympathetic nerve activity and blood pressure were recorded. Bilateral microinjections of IPP to hypothalamic paraventricular nucleus (PVN) attenuated sympathetic activity (-16.1 ± 2.5%, P < 0.001) and hypertension (-8.7 ± 1.5 mmHg, P < 0.01) in 2K1C rats by inhibiting ACE activity and subsequent angiotensin II and superoxide production in the PVN. Intravenous injections of IPP also attenuated sympathetic activity (-15.1 ± 2.1%, P < 0.001) and hypertension (-16.8 ± 2.3 mmHg, P < 0.001) via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. The duration of the effects of the intravenous IPP was longer than those of the PVN microinjection, but the sympatho-inhibitory effect of intravenous injections occurred later than that of the PVN microinjection. Intraperitoneal injection of IPP (400 pmol/day for 20 days) attenuated hypertension and vascular remodeling via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. These results indicate that IPP attenuates hypertension and sympathetic activity by inhibiting ACE activity and oxidative stress. The sympathoinhibitory effect of peripheral IPP is mainly caused by the ACE inhibition in PVN, and the antihypertensive effect is related to the sympathoinhibition and the arterial ACE inhibition. Long-term intraperitoneal IPP therapy attenuates hypertension, oxidative stress and vascular remodeling.