High Antihypertensive Activity Research Articles

Angiotensin I-Converting Enzyme (ACE-I) Inhibition and Antioxidant Peptide from a Squilla Species.

Oratosquilla woodmasoni is one of the marine squilla species, which is found in the entire Asia-Pacific region. This current study assesses the species as the main basis of both ACEi and antioxidant peptide. To isolate the ACEi peptide derived from O. woodmasoni and examine its ACE inhibition along with antioxidant potential. The squilla muscle protein was hydrolysed using alcalase and trypsin enzymes for 12 hours and tested for DH. The hydrolysates were examined for their ACEi activity and then the best hydrolysate was sequentially purified in various chromatographical methods. The purified peptide was studied for anti-oxidant and functional properties, followed by amino acid sequencing. The purified peptide was also evaluated for its toxicity by in vitro cell viability assay. The DH% was found to be 47.13 ± 0.72% and 89.43 ± 2.06% for alcalase and trypsin, respectively. The alcalase 5th-hour hydrolysate was detected with potent activity (65.97 ± 0.56%) using ACEi assay and was primarily fractionated using ultrafiltration; the maximum inhibitory activity was found with 77.04 ± 0.52% in 3-10 kDa fraction. Subsequently, the fraction was purified using IEC and GFC, in which the AC1-A2 fraction had higher antihypertensive activity (70.85 ± 0.78%). The non-toxic fraction showed hexapeptide HVGGCG with molecular weight 529 Da with great potential of antioxidant activity along with functional property. This peptide could be developed as a potential ACE-inhibitory and antioxidant agent.

Multifunctional hydrolysates from kenaf (Hibiscus cannabinus L.) seed protein with high antihypertensive activity in vitro and in vivo

Kenaf (Hibiscus cannabinus L.) seed is an underutilized protein-rich resource considered as a by-product of the kenaf fiber processing industry. Its high protein content (34%) makes it a promising candidate as a source of bioactive protein hydrolysates. In this study, the potential of enzymatically hydrolyzed kenaf seed protein to generate multifunctional bioactive peptides was evaluated. Kenaf seed protein concentrate was hydrolyzed using four different proteolytic enzymes (papain, alcalase, bromelain, and flavourzyme) at their respective optimum pH and temperature. The choice of enzyme affected the bioactivities to a certain degree as KSPH were shown to possess high ACE inhibitory activity and low-to-moderate DPP-IV and antioxidant activity. Papain KSPH showed the highest ACE inhibitory activity with 95% inhibition compared to other enzymatic hydrolysates, and therefore was chosen for further investigation of its antihypertensive activity. Papain KSPH was profiled for its hydrophobicity by RP-HPLC and revealed that the majority of late-eluting fractions exerted the highest ACE inhibitory activity. Spontaneously hypertensive rats showed a decrease of approximately 18–46 mmHg in their systolic blood pressure (BP) from 0 to 24 h after oral administration of papain KSPH at dosages of 100 mg/kg, 300 mg/kg, and 500 mg/kg. However, the effect was not dose-dependent. As a novel protein source, future research should aim to demonstrate the safety of kenaf seed protein and its hydrolysates, and validate its bioactivity through human intervention trials. Overall, kenaf seed protein has the potential to generate antihypertensive hydrolysates with multifunctional bioactivities as part of a functional food ingredient.

Use of amlodipine + ramipril single-pill combination for prevention of stroke in hypertension patient (clinical case)

Arterial hypertension is one of the most significant modifiable risk factors for stroke. The article provides a clinical example of using a fixed combination of amlodipine + ramipril in real clinical practice in a patient suffering from arterial hypertension, occurring with dyslipidemia, hyperuricoemia, microalbuminuria. High antihypertensive activity of a fixed combination of amlodipine + ramipril was shown. A literature review of the beneficial effect of amlodipine and lisinopril on the risk of stroke, as well as the beneficial effect of this combination of drugs on the course of chronic kidney disease developing in patients with arterial hypertension, is presented.

Оптимальная комбинация Лизиноприла и Амлодипина для лечения пациентов с артериальной гипертонией

Arterial hypertension (AH) remains one of the most common diseases in the world. Reducing cardiovascular risk of mortality from cardiovascular complications is a priority in the treatment of hypertension. Targets of hypertension therapy is to achieve SBP/DBP <140/80 mm Hg. article, regardless of cardiovascular risk and comorbidity. The choice of antihypertensive therapy depends on blood pressure levels, the presence or absence of concomitant diseases, lesion of target organs. Effective and long-lasting control of AH proved by the use of combinations of antihypertensive drugs, including antagonists and ACE inhibitors. The purpose of the study. Evaluation of clinical efficacy and safety of fixed combination antihypertensive therapy using lisinopril combined with amlodipine in patients with hypertension. Material and methods. The study included 30 respondents from essential hypertension II-III degree (ESH/ESC, 2018) aged 35 to 75 years. Patients were treated with the schema a (lisinopril 10 mg, amlodipine 5 mg) and scheme b (lisinopril 20 mg, amlodipine 10 mg) fixed combination therapy with the drug VivaCor® once in the morning. The period of observation was 3 months. At the time of inclusion and at the end of the study all respondents was performed echocardiography, daily monitoring of blood pressure, evaluation of laboratory and instrumental methods of research. Results and discussion. The combination of lisinopril with amlodipine has a fairly high antihypertensive activity, provides a significant cardioprotective effect and is an integral part of antihypertensive therapy in the long-term strategy of administering patients with high hypertensive / very high total cardiovascular risk. Conclusions: 1. The use of a fixed combination of lisinopril and amlodipine in patients with hypertension instead of free or other two-component combinations leads to its target level within 3 months of therapy. 2. Taking a fixed combination of lisinopril and amlodipine is effective and safe. 3. Therapy using the combined drug VivaCor® in patients with high / very high risk of hypertension prevents further pathological remodeling of the heart. 4. The combination of amlodipine and lisinopril is metabolically neutral and well tolerated by patients. Keywords: arterial hypertension, lisinopril, amlodipine, VivaCor.

In Silico identification of angiotensin-converting enzyme inhibitory peptides from MRJP1.

Hypertension is considered as one of the most common diseases that affect human beings (both male and female) due to its high prevalence and also extending widely to both industrialize and developing countries. Angiotensin-converting enzyme (ACE) has a significant role in the regulation of blood pressure and ACE inhibition with inhibitory peptides is considered as a major target to prevent hypertension. In the current study, a blood pressure regulating honey protein (MRJP1) was examined to identify the ACE inhibitory peptides. The 3D structure of MRJP1 was predicted by utilizing the threading approach and further optimized by performing molecular dynamics simulation for 30 nanoseconds (ns) to improve the quality factor up to 92.43%. Root mean square deviation and root mean square fluctuations were calculated to evaluate the structural features and observed the fluctuations in the timescale of 30 ns. AHTpin server based on scoring vector machine of regression models, proteolysis and structural characterization approaches were implemented to identify the potential inhibitory peptides. The anti-hypertensive peptides were scrutinized based on the QSAR models of anti-hypertensive activity and the molecular docking analyses were performed to explore the binding affinities and potential interacting residues. The peptide "EALPHVPIFDR" showed the strong binding affinity and higher anti-hypertensive activity along with the global energy of -58.29 and docking score of 9590. The aromatic amino acids especially Tyr was observed as the key residue to design the dietary peptides and drugs like ACE inhibitors.

The possibilities of angiotensin receptor blocker azilsartan medoxomil and its combination with chlortalidone in cardiovascular risk decrease in patients with obesity, metabolic syndrome and diabetes mellitus

Angiotensin receptor blockers (ARBs) are with increasing frequency used in arterial hypertension treatment, this class of medications is especially important in treatment of patients with obesity, metabolic syndrome and diabetes mellitus. Although not all the ARBs are the therapy of first choice in these patients. The special requirements are imposed upon antihypertensive mediations for patients with arterial hypertension and metabolic disorders such as high antihypertensive activity, maximum duration of action, possibility of increase of peripheral tissues sensitivity to insulin and, subsequently, metabolic profile. Besides, these patients require the use of combined therapy already at the treatment start. There are very few ARBs combinations with thiazide diuretics that exhibit these properties. The present review discusses possibilities of new ARB azilsartan medoxomil (Edarbi®) and its combination with chlortalidone (Edarbi® Clo) in decrease of cardiovascular risk in patients with obesity, metabolic syndrome and diabetes mellitus.

ACE Inhibitory and Antioxidative Bioactive Peptides Derived from Hydrolyzed Soy Milk

Soy milk is a soybean processed product rich in protein as well as sources of bioactive peptides. Bioactive peptides defined as specific protein fragments that have a positive impact on body functions and conditions and may ultimately influence health. This study was conducted to explore the potential of hydrolyzed soy milk as a source of antioxidative and antihypertensive bioactive peptides through enzymatic hydrolysis. The initial treatment of soy milk protein was acidic precipitation with hydrochloric acid. Furthermore, protein precipitate was hydrolyzed using pepsin proteolytic enzyme with an enzyme: substrate ratio (1:5, 1:10 and 1:20). Protein hydrolysis was carried out for 0–48 hours at 37 °C in an acetate buffer pH 4.5. The soy milk protein hydrolysates were subjected to determination of % DH (Degree of Hydrolysis) and protein profile by SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis). The antihypertensive assay was carried out by in vitro inhibition of the ACE enzyme (Angiotensin Converting Enzyme) and antioxidative activity assay using the DPPH method. The results showed that the optimum conditions for hydrolysis of soy milk were obtained at 40 hours with a % DH value of 53.24% in enzyme ratio 1:20 and the highest antihypertensive activity was obtained from 48 hours hydrolysis with % ACE inhibition value of 79.31%. The highest antioxidative activity of bioactive peptide was obtained at hydrolysis 48 hours with IC50 69.1034 µg / ml. After fractionated and LCMS characterized it was obtained 2 bioactive peptides with molecular weights of 8.954 and 2,696 kDa. These bioactive peptides from hydrolyzed of soymilk might be potential as an antihypertensive agent and reduce oxidative stress.

Antioxidant, antihypertensive, anti-hyperglycemic, and antimicrobial activity of aqueous extracts from twelve native plants of the Yucatan coast.

Looking for a biotechnical potential, aqueous extracts of leaves of 12 native species used in the Mayan traditional medicine of the coastal dune and mangrove of Yucatan (Mexico) were selected to evaluate their biological activities. Rhizophora mangle and Manilkara zapota showed the highest free radical scavenging activity (3.94 ± 0.19 and 6.42 ± 0.32 μg/mL, respectively), and the highest antihypertensive activity was obtained from Solanum donianum (0.38 μg/mL). The anti-hyperglycemic activity of these species was also tested; the highest activities were registered with R. mangle. The antimicrobial activity of Malvaviscus arboreus, S. donianum, M. zapota, and R. mangle at 10% (w/v) was positive against six human pathogenic bacteria and Bonellia macrocarpa against one pathogenic fungus. Solanum donianum, M. zapota, B. macrocarpa, and R. mangle were positive against two pathogenic plant fungi. These results show that the aqueous extracts of five native plants of the Yucatan coast have potential as antioxidants, ACE inhibitors, α-amylase and α-glucosidase inhibitors, and as antimicrobials, which make their exploration for utilization in the agricultural and pharmaceutical industries a possibility.

High Throughput Identification of Antihypertensive Peptides from Fish Proteome Datasets.

Antihypertensive peptides (AHTPs) are a group of small peptides with the main role to block key enzymes or receptors in the angiotensin genesis pathway. A great number of AHTPs have been isolated or digested from natural food resources; however, comprehensive studies on comparisons of AHTPs in various species from the perspective of big data are rare. Here, we established a simplified local AHTP database, and performed in situ mapping for high throughput identification of AHTPs with high antihypertensive activity from high-quality whole proteome datasets of 18 fish species. In the 35 identified AHTPs with reported high activity, we observed that Gly-Leu-Pro, Leu-Pro-Gly, and Val-Ser-Val are the major components of fish proteins, and AHTP hit numbers in various species demonstrated a similar distributing pattern. Interestingly, Atlantic salmon (Salmo salar) is in possession of far more abundant AHTPs compared with other fish species. In addition, collagen subunit protein is the largest group with more matching AHTPs. Further exploration of two collagen subunits (col4a5 and col8a1) in more fish species suggested that the hit pattern of these conserved proteins among teleost is almost the same, and their phylogeny is consistent with the evolution of these fish species. In summary, our present study provides basic information for the relationship of AHTPs with fish proteins, which sheds light on rapid discovery of marine drugs or food additives from fish protein hydrolysates to alleviate hypertension.

Antihypertensive and Antioxidant Properties from Whey Protein Hydrolysates Produced by Encapsulated Bacillus subtilis Cells

The proteolytic action from encapsulated Bacillus subtilis cells into polymeric system based in sodium alginate-chitosan-poly (ethylene glycol) (SA/CS/PEG) was evaluated to produce whey protein hydrolysates with antihypertensive and antioxidant properties. Polymeric system SA/CS/PEG resulted in an adequate composite material for the encapsulation of B. subtilis cells. The capsules showed porosity, resistance to agitation and they did not show material leakage and cells leakage. The proteolysis from encapsulated B. subtilis was comparable with the hydrolysis by whole free B. subtilis cells, achieving approximately 40% of hydrolysis of whey proteins after of 6 h. In addition, the proteolysis was maintained during various cycles of hydrolysis, without a drastic reduction of the enzymatic activity. The hydrolisate products included two peptidic fractions; peptides up 11 kDa and those of smaller size than 3 kDa. Peptides than 3 kDa showed high antihypertensive and antioxidant activity (82.33 and 76.54% respectively), and a great contained of amino acids, which were associated to these biological properties.

The control of blood pressure level as the prevention of cognitive impairment

Today the prevalence of cognitive impairment is a large scale. At the end of the pathological process partial or complete, social, professional and common maladjustment and disability comes. One of the main factors of progression of cognitive impairment is a decrease in adherence to the therapy, forming a vicious circle of the underlying disease and its complications. In the article we examine the prevalence, pathogenesis and classification of cognitive impairment of patients with arterial hypertension, memory impairment, analyze the relationship of high blood pressure numbers. The use of modern antihypertensive drugs, with adequate control of blood pressure reduces the risk of development and progression of cognitive impairment. To this end, successfully it can be used calcium channel blocker lercanidipine third generation, which has high anti-hypertensive activity, cerebroprotective function, causing regression of cognitive disorders, enhancing the quality of life of patients. Nowadays there is a small number of studies investigating the effect of calcium channel blockers on cognitive function, that led to the study of this issue.

Контроль уровня артериального давления как профилактика когнитивных нарушений

Today the prevalence of cognitive impairment is a large scale. At the end of the pathological process partial or complete, social, professional and common maladjustment and disability comes. One of the main factors of progression of cognitive impairment is a decrease in adherence to the therapy, forming a vicious circle of the underlying disease and its complications. In the article we examine the prevalence, pathogenesis and classification of cognitive impairment of patients with arterial hypertension, memory impairment, analyze the relationship of high blood pressure numbers. The use of modern antihypertensive drugs, with adequate control of blood pressure reduces the risk of development and progression of cognitive impairment. To this end, successfully it can be used calcium channel blocker lercanidipine third generation, which has high anti-hypertensive activity, cerebroprotective function, causing regression of cognitive disorders, enhancing the quality of life of patients. Nowadays there is a small number of studies investigating the effect of calcium channel blockers on cognitive function, that led to the study of this issue.

Антигипертензивные эффекты фиксированной комбинации лизиноприла и амлодипина у больных ишемической болезнью сердца после коронарного шунтирования

Literature data and results of our own register have indicate that hypertension is one of the most common risk factor in patients with ischemic heart disease (IHD) who have undergone coronary artery bypass grafting (CABG). But despite proven benefits of control of hypertension after CABG adherence of patients to corresponding recommendations remains low. Fixed combinations of antihypertensive drugs are associated with better compliance. In 30 IHD patients after CABG we studied effects of fixed lisinopril/amlodipine combination. This combination was safe and had high antihypertensive activity. Practically all patients responded to therapy and achieved target level of arterial pressure.

Biological Properties of Fucoxanthin in Oil Recovered from Two Brown Seaweeds Using Supercritical CO2 Extraction.

The bioactive materials in brown seaweeds hold great interest for developing new drugs and healthy foods. The oil content in brown seaweeds (Saccharina japonica and Sargassum horneri) was extracted by using environmentally friendly supercritical CO2 (SC-CO2) with ethanol as a co-solvent in a semi-batch flow extraction process and compared the results with a conventional extraction process using hexane, ethanol, and acetone mixed with methanol (1:1, v/v). The SC-CO2 method was used at a temperature of 45 °C and pressure of 250 bar. The flow rate of CO2 (27 g/min) was constant for the entire extraction period of 2 h. The obtained oil from the brown seaweeds was analyzed to determine their valuable compounds such as fatty acids, phenolic compounds, fucoxanthin and biological properties including antioxidant, antimicrobial, and antihypertension effects. The amounts of fucoxanthin extracted from the SC-CO2 oils of S. japonica and S. horneri were 0.41 ± 0.05 and 0.77 ± 0.07 mg/g, respectively. High antihypertensive activity was detected when using mixed acetone and methanol, whereas the phenolic content and antioxidant property were higher in the oil extracted by SC-CO2. The acetone–methanol mix extracts exhibited better antimicrobial activities than those obtained by other means. Thus, the SC-CO2 extraction process appears to be a good method for obtaining valuable compounds from both brown seaweeds, and showed stronger biological activity than that obtained by the conventional extraction process.

Characterization, Antibacterial and Biological Activities of Phenolic Fraction of Argentinean Red Wines

Fil: Stivala, Maria Gilda. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

Characteristics of Two Unrecorded Yeasts from Wild Flowers in Ulleungdo, Korea

Two unrecorded yeasts, Meyerozyma caribbica UL5-1 and Pichia silvicola UL6-1 were screened from 58 yeasts which were isolated from wild flowers in Ulleungdo in Gyeongsangbuk-do, Korea. The morphological and cultural characteristics of these unrecorded yeasts were investigated. Both yeasts were oval in shape and formed pseudomycelia. P. silvicola UL6-1 formed ascospore, but M. UL5-1 did not. P. silvicola UL6-1 and M. caribbica UL5-1 also grew in vitamin-free medium and 5% NaCl-containing yeast extract-peptone-dextrose medium. The two unrecorded yeasts assimilated glucose, galactose, xylose, cellobiose, trehalose, glycerol and sorbitol, and also fermented glucose, fructose and mannose. The supernatant of both M. caribbica UL5-1 and P. silvicola UL6-1 showed high antihypertensive angiotensin I-converting enzyme inhibitory activity of 84.2% and 82.6%, respectively. Cell-free extract of P. silvicola UL6-1 also showed very high anti-diabetic <TEX>${\alpha}$</TEX>-glucosidase inhibitory activity (85.8%).

Development of a capillary high performance liquid chromatography–ion trap-mass spectrometry method for the determination of VLIVP antihypertensive peptide in soybean crops

Soybean peptide VLIVP presents a very high antihypertensive activity (IC50 value 1.69μM), even higher than extensively studied IPP and VPP peptides from milk. Nevertheless, no much attention has been paid to this peptide and there is no method enabling its determination in soybeans. The aim of this work was the development of an analytical methodology for this purpose. A methodology consisting of the extraction of soybean proteins, their digestion with Protease P enzyme, their chromatographic separation using capillary-HPLC, and IT-MS detection was optimized. Protein extraction was performed by the use of high intensity focused ultrasounds to obtain a reduced extraction time. Optimization of chromatographic and mass spectrometry parameters enabled the separation of VLIVP peptide within just 7min and its sensitive detection. The analytical characteristics of the capillary-HPLC–IT-MS method were evaluated through the study of linearity, LOD, LOQ, study of the presence of matrix interferences, precision, and recovery. The method enabled to detect as low as 3.6ng of peptide and to determine as low as 12ng of peptide in 1g of soybean (as dry basis). Finally, the developed method was applied to the determination of the antihypertensive peptide VLIVP in different soybean varieties. The results showed the highest yield of VLIVP peptide in variety Mazowiecka II from Poland.

Biofilm Inhibition of Spoilage Bacteria by Argentinean Fruit Juices with Antihypertensive Activity

Argentinean juices have been studied for their antihypertensive activity, the inhibition of bacteria biofilm formation and the effect on the viability of wine yeast. The influence of phenolic compounds on these activities was evaluated. These studies are the first step for the development of a new type of wine that includes grape must supplement with fruit juices with antihypertensive effect. All juices posses a high antihypertensive activity, higher than 50%. Strawberry juices and eureka lemon showed the highest activity, whereas clarified juices posses the lowest activity. All studied juices produce a high inhibition of bacteria biofilm formation, and the strawberry, orange and mandarin varieties not affect the growth or viability of yeast. Our results permit to conclude that it could be possible the use of these juices in a new type of wine or as a source of new antihypertensive agents for pharmaceutical industry.

Use of diuretics in hypertensive patients with metabolic disturbances

The multicenter research MERSY (Moxonidine Efficacy on blood pressure Reduction revealed in a metabolic SYndrome population) finished in 2008 was devoted to an assessment of long-term safety and efficiency of agonist I2-imidazolin receptors – moxonidine in patients with arterial hypertension and metabolic syndrome (in the general group and in advance defined subgroup of patients in a postmenopause). In 2013 final international results of the research MERSY which showed high antihypertensive activity of moxonidine, and also its positive influence on metabolic parameters and mass of a body were published.

What are the ideal properties for functional food peptides with antihypertensive effect? A computational peptidology approach

Peptides with antihypertensive potency have long been attractive to the medical and food communities. However, serving as food additives, rather than therapeutic agents, peptides should have a good taste. In the present study, we explore the intrinsic relationship between the angiotensin I-converting enzyme (ACE) inhibition and bitterness of short peptides in the framework of computational peptidology, attempting to find out the appropriate properties for functional food peptides with satisfactory bioactivities. As might be expected, quantitative structure–activity relationship modeling reveals a significant positive correlation between the ACE inhibition and bitterness of dipeptides, but this correlation is quite modest for tripeptides and, particularly, tetrapeptides. Moreover, quantum mechanics/molecular mechanics analysis of the structural basis and energetic profile involved in ACE–peptide complexes unravels that peptides of up to 4 amino acids long are sufficient to have efficient binding to ACE, and more additional residues do not bring with substantial enhance in their ACE-binding affinity and, thus, antihypertensive capability. All of above, it is coming together to suggest that the tripeptides and tetrapeptides could be considered as ideal candidates for seeking potential functional food additives with both high antihypertensive activity and low bitterness.