Search

BACKGROUND: Hypertension is a chronic disease with high morbidity and mortality. Previously, we screened a walnut meal peptide FDWLR (PEP) with significant angiotensin‐converting enzyme inhibitory activity. The present study further investigated the anti‐hypertensive effects of PEP in vivo using spontaneously hypertensive rats. RESULTS: The results indicated that PEP reduced blood pressure and the indices in the renin–angiotensin–aldosterone system (RAAS) including angiotensin‐converting enzyme (ACE) (decreased by 15.36%), angiotensin II (Ang II) (decreased by 31.56%), angiotensinogen (AGT) (decreased by 58.84%) and aldosterone (ALD) (decreased by 18.27%), whereas NO levels increased by 54.96%. The pathological analysis showed that PEP relieved cardiac and renal damage. PEP also alleviated oxidative stress, inflammation and fibrosis in the heart and kidney. Mechanistically, PEP mitigated cardiac and renal damage by simultaneously regulating ACE‐Ang II‐AT1R and the ACE2‐Ang (1–7)‐MAS axis. Additionally, PEP increased the levels of short chain fatty acids by 224.16% and improved gut microbiota by increasing the abundance of Prevotella, Phascolarctobacterium, Clostridium_sensu_stricto and Bifidobacterium, at the same time as decreasing Bacteroides and Alistipes abundances. CONCLUSION: This study indicated that PEP prevented hypertension and associated heart and kidney damage by modulating the RAAS system and gut microbiota, which is valuable in guiding future development and optimal utilization of walnut meal. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Fewer than one-half of U.S. adults with hypertension (HTN) have it controlled and one-third are unaware of their condition. The emergency department (ED) represents a setting to improve HTN control by increasing awareness of asymptomatic hypertension (aHTN) according to the 2013 American College of Emergency Physicians asymptomatic elevated blood pressure clinical policy. The aim of the study was to estimate the prevalence and management of aHTN in U.S. EDs. We examined the 2016–2019 National Hospital Ambulatory Medical Care Surveys to provide a more valid estimate of aHTN visits in U.S. EDs. aHTN is defined as adult patients with blood pressure ≥ 160/100 mm Hg at triage and discharge without trauma or signs of end organ damage. We then stratified aHTN into a 160–179/100–109 mm Hg subgroup and > 180/110 mm Hg subgroup and examined diagnosis and treatment outcomes. Approximately 5.9% of total visits between 2016 and 2019 met the definition for aHTN and 74% of patients were discharged home, representing an estimated 26.5 million visits. Among those discharged home, emergency physicians diagnosed 13% (95% CI 10.6–15.8%) and treated aHTN in 3.9% (95% CI 2.8–5.5%) of patients in the higher aHTN subgroup. In the lower aHTN subgroup, diagnosis and treatment decreased to 3.1% (95% CI 2.4–4.1%) and 1.2% (95% CI 0.7–2.0%), respectively. Millions of ED patients found to have aHTN are discharged home without diagnosis or treatment. Although management practices follow clinical policy to delay treatment of aHTN, there are missed opportunities to diagnosis aHTN. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the in vivo anti-hypertensive activity and the intestinal microbiota regulation of yeast protein hydrolysate (YH) on spontaneous hypertensive rat (SHR). The YH was produced by alkali protease hydrolysis and ultrafiltration, with the ACE inhibitory IC 50 of 0.11 mg/mL. Treatment with 200 mg/kg BW and 400 mg/kg BW of YH resulted in 12 and 17 mmHg of decrease in systolic blood pressure (SBP), respectively, at 4 h after the first administration. For 4-week administration, both dosages of the YH could decrease about 20 mmHg of SBP compared with untreated SHRs. The YH modulated blood pressure by inhibiting serum ACE activity, lowering Ang II content, and upregulating the expression of AT2R at the higher dose. The YH also alleviated oxidative stress in SHRs, significantly elevating serum GSH (24%) and reducing MDA content (50%). In addition, the YH could restore the gut microbiota dysbiosis of SHR, and increased the titer of fecal short-chain fatty acids (SCFAs) as well as the relative abundance of SCFA producing bacteria, including Roseburia , Bacteroides , Ruminococcaceae_UCG-005 , Ruminococcaceae_UCG-014 and Alloprevotella. According to the correlation analysis, significant relevances among blood pressure, serum ACE activity, Ang II level, oxidative stress, fecal SCFAs, and gut microbiota in SHR were found. Therefore, YH is a promising functional component in lowering blood pressure and regulating intestinal microbiota. [Display omitted] • Yeast hydrolysate (YH) showed high ACE inhibition with the IC 50 of 0.11 mg/mL. • High and low dose of YH show significant acute and subacute antihypertensive effect. • YH reduced blood pressure by modulating RAS-KKS and ameliorating oxidative stress. • YH restored the gut microbiota disturbances and increased SCFA-producing bacteria. • Negative correlation between diversity of gut microbiota, SCFAs and blood pressure. [ABSTRACT FROM AUTHOR]

Hypertension knowledge and medication adherence are the success of treatment. We aimed to determine the association between knowledge about hypertension and medication adherence in hypertensive patients. A crosssectional study was conducted in in-person interviews with 360 hypertensive patients using a pre-designed questionnaire. The Hypertension Knowledge-Level Scale (HK-LS) assessed patients' knowledge about hypertension. The Morisky Medication Adherence Scale assessed patients' medication adherence. Patients' characteristics and medication usage data were obtained from medical records or prescriptions. The mean age of the patients was 59.3±9.55 years. Most patients used only one antihypertensive medication (74.7%), and a calcium channel blocker was the most used (46.4%). Many patients in this study had poor knowledge about hypertension, accounting for 65.28%, though most patients adhered to medication (81.94%). Patients' knowledge of hypertension had a statistically significant association with medication adherence (p=0.002). This research indicated the association between knowledge and medication adherence, so medical personnel consultation is crucial to raise patients' knowledge and improve treatment safety. [ABSTRACT FROM AUTHOR]

Sugarcane, a globally cultivated crop constituting nearly 80% of total sugar production, yields residues from harvesting and sugar production known for their renewable bioactive compounds with health-promoting properties. Despite previous studies, the intricate interplay of extracts from diverse sugarcane byproducts and their biological attributes remains underexplored. This study focused on extracting the lipid fraction from a blend of selected sugarcane byproducts (straw, bagasse, and filter cake) using ethanol. The resulting extract underwent comprehensive characterization, including physicochemical analysis (FT-IR, DSC, particle size distribution, and color) and chemical composition assessment (GC-MS). The biological properties were evaluated through antihypertensive (ACE), anticholesterolemic (HMG-CoA reductase), and antidiabetic (alpha-glucosidase and Dipeptidyl Peptidase-IV) assays, alongside in vitro biocompatibility assessments in Caco-2 and Hep G2 cells. The phytochemicals identified, such as β-sitosterol and 1-octacosanol, likely contribute to the extract's antidiabetic, anticholesterolemic, and antihypertensive potential, given their association with various beneficial bioactivities. The extract exhibited substantial antidiabetic effects, inhibiting α-glucosidase (5–60%) and DPP-IV activity (25–100%), anticholesterolemic potential with HMG-CoA reductase inhibition (11.4–63.2%), and antihypertensive properties through ACE inhibition (24.0–27.3%). These findings lay the groundwork for incorporating these ingredients into the development of food supplements or nutraceuticals, offering potential for preventing and managing metabolic syndrome-associated conditions. [ABSTRACT FROM AUTHOR]

Adherence to medication plays a crucial role in the effective management of chronic diseases. However, patients often miss their scheduled drug administrations, resulting in suboptimal disease control. Therefore, we propose an implantable device enabled with automated and precisely timed drug administration. Our device incorporates a built-in mechanical clock movement to utilize a clockwork mechanism, i.e., a periodic turn of the hour axis, enabling automatic drug infusion at precise 12-h intervals. The actuation principle relies on the sophisticated design of the device, where the rotational movement of the hour axis is converted into potential mechanical energy and is abruptly released at the exact moment for drug administration. The clock movement can be charged either automatically by mechanical agitations or manually by winding the crown, while the device remains implanted, thereby enabling the device to be used permanently without the need for batteries. When tested using metoprolol, an antihypertensive drug, in a spontaneously hypertensive animal model, the implanted device can deliver drug automatically at precise 12-h intervals without the need for further attention, leading to similarly effective blood pressure control and ultimately, prevention of ventricular hypertrophy as compared with scheduled drug administrations. These findings suggest that our device is a promising alternative to conventional methods for complex drug administration. [ABSTRACT FROM AUTHOR]

Hypertension is a common disease that affects human health and can lead to damage to the heart, kidneys, and other important organs. In this study, we investigated the regulatory effects of bioactive peptides derived from Ruditapes philippinarum (RPP) on hypertension and organ protection in deoxycorticosterone acetate (DOCA)–salt hypertensive rats. We found that RPPs exhibited significant blood pressure-lowering properties. Furthermore, the results showed that RPPs positively influenced vascular remodeling and effectively maintained a balanced water–sodium equilibrium. Meanwhile, RPPs demonstrated anti-inflammatory potential by reducing the serum levels of inflammatory cytokines (TNF-α, IL-2, and IL-6). Moreover, we observed the strong antioxidant activity of RPPs, which played a critical role in reducing oxidative stress and alleviating hypertension-induced damage to the aorta, heart, and kidneys. Additionally, our study explored the regulatory effects of RPPs on the gut microbiota, suggesting a possible correlation between their antihypertensive effects and the modulation of gut microbiota. Our previous studies have demonstrated that RPPs can significantly reduce blood pressure in SHR rats. This suggests that RPPs can significantly improve both essential hypertension and DOAC–salt-induced secondary hypertension and can ameliorate cardiorenal damage caused by hypertension. These findings further support the possibility of RPPs as an active ingredient in functional anti-hypertensive foods. [ABSTRACT FROM AUTHOR]

One of the most striking aspects of the primary structure in the hydrophobic domains of the tropoelastin molecule is the occurrence of the VAPGVG repeating sequence. Since the N-terminal tripeptide VAP of VAPGVG showed a potent ACE inhibitory activity, the ACE inhibitory activity of various derivatives of VAP was examined in vitro. The results showed that VAP derivative peptides VLP, VGP, VSP, GAP, LSP, and TRP exhibited potent ACE inhibitory activities, while the non-derivative peptide APG showed only weak activity. In in silico studies, the docking score S value showed that VAP derivative peptides VLP, VGP, VSP, LSP, and TRP had stronger docking interactions than APG. Molecular docking in the ACE active pocket showed that TRP, the most potent ACE inhibitory peptide among the VAP derivatives, had a larger number of interactions with ACE residues in comparison with APG and that the TRP molecule appeared to spread widely in the ACE pocket, while the APG molecule appeared to spread closely. Differences in molecular spread may be a reason why TRP exhibits more potent ACE inhibitory activity than APG. The results suggest that the number and strength of interactions between the peptide and ACE are important for the ACE- inhibitory potency of the peptide. [ABSTRACT FROM AUTHOR]

Aliskiren is referred to as a direct renin inhibitor. renin catalysis the conversion of angiotensinogen to angiotensin-1 Aliskiren and Valsartan use as hypertension. Valsartan belongs to the angiotensin 2 receptor blocker family. Which prevent the protein angiotensin 2. Cardiac stimulation and renal reabsorption of sodium. This review article represents the collection and discussion of various analytical methods available in the literature for the determination of Aliskiren and Valsartan in pharmaceutical and biological samples consisting of UV spectroscopy, RP-HPLC, HPTLC, LCMS/MS methods. The anticipated review provides details about the comparative utilization of various analytical techniques for the determination of Aliskiren and Valsartan alone and in combination. The present review article can be effectively explored to conduct future analytical investigation for the estimation of Aliskiren and Valsartan. [ABSTRACT FROM AUTHOR]

Bioactive peptides (BPs) generated by enzymatic hydrolysis possess diverse biological properties. In recent years, reports on novel BPs derived from both food and non-food protein sources, such as animals, plants, fermented food products, and microorganisms, have drastically increased. The biological activities of BPs include antioxidant, antihypertensive, antimicrobial, antidiabetic, immomodulatory, opioid, and anticancer properties, among others. Of these, BPs with antioxidative and antihypertensive properties have been studied the most, but their tests were commonly conducted in vitro. Since the mechanism of their biological functions and safety in real situations might be required to support health claims, future research on BPs with the aforementioned activities and/or alternative functions should employ in vivo models and human subjects. Furthermore, the cost of production and formulation for stability should be evaluated prior to commercialization. [ABSTRACT FROM AUTHOR]

Fermented soybean curds (FSC) are popular because of its umami taste. Its bioactivities are of interest. Peptides in FSC were identified using nano-HPLC-MS/MS, and 11 candidate peptides showing potential umami and ACE inhibitory activities were screened using various databases. Pharmacophore model analysis showed their high probability of ACE inhibition with fit values >2, which showed the peptides bound to umami receptors and ACE mainly through hydrogen bond, and electrostatic and hydrophobic interactions. Additionally, their docking and interaction energy were independent of the peptide length. Three high umami-ACE inhibitory peptides (VE, FEF, and WEEF) were synthesized. Their umami thresholds were WEEF (0.32 mM) < FEF (0.55 mM) < VE (1.10 mM), while their IC 50 were WEEF (85 ± 2 μM) < FEF (170 ± 10 μM) < VE (205 ± 5 μM). NO and ET-1 production were dose-dependent with WEEF showing the best ACE inhibitory activity. The results allowed identification of effective umami agents and ACE inhibitory peptides from fermented soybean products. It could also be useful method for screening potential umami-ACE inhibitory peptides. [Display omitted] • 11 umami-ACE inhibitory peptide candidates were screened from FSC. • Dipeptides mainly activated the T1R1 sites. • Tripeptides and tetrapeptides activated the T1R3 sites. • WEEF (Trp-Glu-Glu-Phe) was an effective umami agent and ACE inhibitor from FSC. [ABSTRACT FROM AUTHOR]

We studied angiotensin I converting enzyme (ACE) inhibitory effect of the protein hydrolysates prepared from commercially available nori products that contain Pyropia pseudolinearis as the main ingredient. The water extract of the nori product consisted mainly of phycobiliproteins and RubisCO. The proteins in the aqueous extracts were sequentially hydrolyzed with pepsin and trypsin, and the peptides in the pepsin–trypsin digests were fractionated by reversed-phase HPLC. As a result, 12 ACE inhibitory peptides containing ten novel peptides were identified. These peptides are suggested to have originated from the α- and β-subunits of phycobiliproteins and the large subunits of RubisCO of P. pseudolinearis. The interactions of eight peptides (ALR, FAR, FSR, FDR, EVYR, AYR, GRP, and MVT) with ACE were then simulated using the flexible docking tool Auto Dock Vina. The results showed that all peptides interacted with the active center of ACE, and their docking scores ranged from − 6.8 to − 10.2 kcal/mol. In addition, we synthesized four peptides (AYR, FAR, EVYR, and GRP) and measured the IC50 values of these peptides for ACE. Consequently, FAR and GRP showed considerably low IC50 values (0.29 μmol and 0.45 μmol, respectively) in addition to other ACE inhibitory peptides. Moreover, FAR, which is specific to the nori product, was predicted to bind to the S1, S1′, and S2′ subsites of the catalytic center of ACE. Therefore, it can be expected that daily intake of "nori products" may have a positive effect on the prevention of hypertension. [ABSTRACT FROM AUTHOR]

In Indonesia, hypertension is a condition that can lead to death through stroke and TB. Herbs have traditionally been used in Indonesia as an alternative medicine for lowering blood pressure. The leaves of Anredera cordifolia and Sonchus arvensis have been investigated for their antihypertensive potential. Based on the number of treatments, rats were randomized into groups. Each group consists of five rats. The test animals were grouping as follows: the positive control group (hypertension induction without treatment), A. cordifolia 50 mg/kg b.w. group, A. cordifolia 100 mg/kg b.w., S. arvensis 50 mg/kg b.w, S. arvensis 100 mg/kg b.w., A. cordifolia 25 mg/kg b.w + S. arvensis 25 mg/kg b.w, A. cordifolia 50 mg/kg b.w + S. arvensis 50 mg/kg b.w, and atenolol 4.5 mg/kg b.w. The rats were given 0.25 mg/kg b.w. of epinephrine intraperitoneally. The initial, after induction, and final blood pressure of the animals were measured using the CODA® noninvasive blood pressure device. All animal test groups at T60 showed a significant difference in systolic and diastolic blood pressures to initial blood pressure (T0), P < 0.05. The combination of A. cordifolia 50 mg/kg b.w and S. arvensis 50 mg/kg b.w showed the highest percent inhibition of systolic and diastolic blood pressure. The combination of A. cordifolia and S. arvensis 50–50 mg/kg b.w showed the best effect of lowering systolic and diastolic blood pressure on the pathway of inhibiting adrenergic receptors. [ABSTRACT FROM AUTHOR]

Arbutus unedo also known as the strawberry tree is an evergreen shrub very appreciated in the Mediterranean area, however, it is still considered as an underexploited tree. Due to its various benefits, ethnobotanicals, chemists, nutritionists and anthropologists are more and more interested in it. It belongs to Erecaceae family and it is abundant, especially all over the Mediterranean sea and in other hotsummer and rainy-winter areas. In a bibliographic and an ethnobotanic study of the strawberry tree, we are going to briefly present the shrub, enumerate its different parts pharmacological properties and its operational fields. In traditional medicine, the fruits are used as antiseptics, diuretics and laxatives and the leaves are known by their diuretics, urinary antiseptics, antidiarrheal, astringent, depurative and antihypertensive properties. The high pharmacological potential was demonstrated by different Arbutus unedo extracts analysis, which provide it with its antidiarrheal, astringent, depurative and antihypertensive properties antifungal, anti-parasitic, antiaggregant, antidiabetic, antihypertensive, anti-inflammatory, antitumoral, antioxidant, and spasmolytic properties. Indeed, fruits, leaves and roots composition of this shrub reveals a promising basis as a phytopharmaceutical product and must motivate researchers to enhance their studies in order to develop innovative drugs. [ABSTRACT FROM AUTHOR]

Korean red pine needle (RPN) exhibits various biological and pharmacological activities. Among the various compounds of RPN, we isolated dehydroabietic and 4-epi-trans-communic acid. At first, we confirmed that two compounds inhibited angiotensin converting enzyme (ACE) and induced p-Akt in human umbilical vein endothelial cells (HUVEC). RPN extract powder significantly reduced systolic blood pressure in spontaneous hypertensive rats (SHRs) through the reduced expression of ACE and angiotensin type I receptors in the lungs of SHRs. The Lineweaver–Burk plots suggested that the two compounds were noncompetitive inhibitors of ACE. Using docking analysis, we found that two compounds showed the best returned pose at ACE active sites, and formed hydrogen and hydrophobic bonds with ACE residues. These results demonstrate that RPNs may be a source of compounds effective for preventing hypertension and may be useful in the development of antihypertensive drugs. [ABSTRACT FROM AUTHOR]

Background: Propolis has been widely reported as having various biological activities. However, Indonesian propolis seems to be less explored. Objective: The present study aimed to analyze the antihypertensive activity of Indonesian propolis in rats. Materials and Methods: Hypertension was induced by high-NaCl (8%) diet for 3 weeks. A total of 36 rats were divided into 6 groups, including standard diet group (SD), high-NaCl diet group (NaD), high-NaCl diet group + captopril (25 mg/ kg) (PD), high-NaCl diet + propolis from Riau Archipelago (NaDP1), high-NaCl diet + propolis from Lampung (NaDP2) and high-NaCl diet + propolis from South Sulawesi (NaDP3). Propolis was daily administered at dose of 200 mg/kg on hypertensive rats for 1 week. Blood pressure and body weight were weekly measured. Moreover, routine urine analysis, haematological parameters and lipid profiles at week 4 were determined. Results: The results showed that high-NaCl diet successfully induced hypertension in rats after 3 weeks of intervention. However, the diet did not cause weight gain (p>0.05). All Indonesian propolis samples significantly reversed either systolic or diastolic blood pressure of hypertensive rats. From urine analysis, propolis from Riau Archipelago and Lampung showed diuretic effect. The haematological analysis mainly showed no significant difference compared standard diet group. Furthermore, LDL and HDL concentrations were significantly improved by propolis from Lampung and South Sulawesi, respectively (p<0.05). In addition, we only found significant decrease in relative weight of liver in all groups administered with high-NaCl diet (p<0.05). Conclusion: The present study suggests that all Indonesian propolis possessed antihypertensive activity. [ABSTRACT FROM AUTHOR]

Angiotensin I converting enzyme (ACE) inhibition is one of the key factors for cardiovascular disease, and inhibition of ACE activity is related to the prevention of high blood pressure. Until now, some ACE inhibitory peptides have been found in the protein hydrolysates of red algae, and most of them were derived from phycobiliproteins and rubisco. In this study, we modified the preparation method to evaluate the potential of ACE inhibitory activity from protein hydrolysate of red alga Mazzaella japonica except for phycobiliproteins and rubisco. As a result, we identified 11 peptides (YRD, VSEGLD, TIMPHPR, GGPAT, SSNDYPI, SRIYNVKSNG, VDAHY, CPYDWV, YGDPDHY, NLGN and DFGVPGHEP) in the hydrolysate by the reversed phase-HPLC and MALDI-TOF/MS/MS. Among them, YRD would be derived from phycoerythrin α-subunit. However, the others would be from other proteins encoded in chloroplast or nuclear genomes. This study revealed that not only phycobiliproteins and rubisco but also the other proteins in red algae have the potential for the source of ACE inhibitory peptide. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a condition, in which a patient's systolic blood pressure reaches =140 mmHg and/or the diastolic blood pressure reaches =90 mmHg. The disease is generally treated using synthetic chemical drugs such as angiotensinconverting enzyme (ACE) inhibitors. In Indonesia, especially the island of Java, people often use medicinal plants called Jamu (herbs) to treat hypertension. One of the most often used medicinal plants to treat hypertension is cantaloupe (Cucumis melo var. cantalupensis) or Blewah in Javanese. However, thus far, the mechanism of how cantaloupe reduces blood pressure is still unknown. Materials and Methods: This research aimed to investigate the working mechanism of cantaloupe in reducing blood pressure through an in silico approach. Results: An enzyme activity analysis showed that the methanol extract from cantaloupe inhibited the activity of ACE in a dose-dependent manner. Moreover, the mapping analysis of the interaction between the bioactive compounds and their target proteins, using the STITCH and STRINGdb databases, suggested that L-glutathione (GSH) (reduced) interacted with proteins that are members of the superfamily of GSH S-transferase (GST). Conclusion: This protein family acts in detoxification and radical scavenging. Thus, the possible working mechanism of cantaloupe in reducing blood pressure is through the detoxification and radical scavenging pathways by GST. [ABSTRACT FROM AUTHOR]

Hypertension is an important risk factor of cardiovascular disease which is the leading cause of death. Traditionally, many plants are used to lower blood pressure including Anredera cordifolia (Ten.) v. Steenis and Sonchus arvensis L. Previous studies found that both plants showed antihypertensive activity through inhibiting angiotensin converting enzyme and inducing diuresis. The aim of this study is to evaluate the antihypertensive effect of Anredera cordifolia (Ten.) v. Steenis leaves extract (ACLE) and Sonchus arvensis L. leaves extract (SALE) combination on hypertensive animal induced with angiotensin II. In this study, blood pressure measurement was done using CODA® tail-cuff blood pressure system plethysmograph. After initial measurement of blood pressure, extracts were administered orally according to the respective groups as follow: ACLE 50, ACLE 100, SALE 50, SALE 100, ACLE-SALE 25-25, and ACLE-SALE 50-50 mg/kg bw. After 1 hour, angiotensin II 100 µg/kg bw was administered then the blood pressure was re-measured. ACLE 50 and ACLE-SALE 25-25 mg/kg bw were able to significantly lower blood pressure compared to positive control group (p<0.05), while SALE 50 mg/kg bw was not. Significant prevention of blood pressure elevation was seen in ACLE-SALE 25-25 mg/kg bw group with percent inhibition of 54.77% for systole and 67.6% diastole. ACLE 50 and ACLE-SALE 25-25 mg/kg bw were able to reduce the effect of angiotensin II and possibly act as angiotensin receptor antagonist. Furthermore, in extract combination, SALE of 25 mg/kg bw could reduce the dose of single ACLE as antihypertension by half the individual dose. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated whether lancemaside A (LMA) can prevent hypertension and assessed the mechanisms of action of LMA in rats. Methods: Hypertension was induced by chronic immobilization stress and nicotine administration. Hypertensive vehicle rats were treated with LMA (1, 20, or 40 mg/kg) or nifedipine (10 mg/kg) as a positive control daily for 3 weeks. Key findings: In hypertensive vehicle rats, LMA dose‐dependently reduced systolic blood pressure. LMA doses of 20 and 40 mg/kg reduced the aortic expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)2 (both P < 0.01), and 40 mg/kg LMA reduced serum malondialdehyde (P < 0.01). Serum nitrite levels were significantly higher in LMA treated rats than in hypertensive vehicle rats, with LMA doses of 20 and 40 mg/kg reducing the expression of endothelial nitric oxide synthase in rat aortas (P < 0.001 and P < 0.01, respectively). LMA also reduced the aortic levels of nuclear factor kappa B and the activation of the three isoforms of mitogen‐activated protein kinase (MAPK). Conclusions: Lancemaside A prevents hypertension in rats by inhibiting the activation of MAPK signalling and the impairment in nitric oxide bioavailability due to NOX2‐mediated oxidative stress. Thus, LMA may act as a preventive agent for hypertension. [ABSTRACT FROM AUTHOR]

Hypertension is a major risk factor for human cardiovascular health, which can damage heart, brain, kidneys, etc. In this study we aimed to develop novel angiotensin II receptor blockers (ARBs) that prevent the increase of blood pressure for treatment of hypertension. (2-(4-((2-Amyl-5-nitro-1H-benzo[d]-imidazol-1-yl) methyl)-1H-indol-1-yl) tetrazole; compound 1a) was one of the ARBs designed and synthesized. It was prepared and orally administered to spontaneous hypertensive rats to study the antihypertensive effects. The maximum reduction in blood pressure reached 50 mmHg after dosing compound 1a for 5 h. Acute toxicity test was carried out on healthy 4 week old 30 male and 30 female ICR mice and LD50 for 1a was found to be 2864.03 mg/kg. High performance liquid chromatography was employed to determine the level of 1a plasma concentration at various time points after administration. The plasma concentration of 1a increased after 2 h, declined gradually and was still detectable in the plasma after 72 h. The drug distribution analysis of 1a was performed on healthy Wistar rats. It was present in the liver with the highest concentration, in kidney with a lower concentration, and in the spleen, lung, heart and brain with the lowest concentration. It displayed high affinity to AT1 receptor, and had an efficient and long-lasting effect in reducing blood pressure, which lasted for more than 12 h. Due to its biological safety, 1a could be absorbed quickly, metabolized smoothly, and can be distributed in important organs. Therefore, 1a could be considered as a suitable ARB candidate for further studies. [ABSTRACT FROM AUTHOR]

Summary: Bioactive peptides are the general name for the short amino acid sequences, which could be generated from the hydrolysis of parent proteins including beef, pork, mutton, chicken, duck and various species of marine organisms. Drying, curing, ripening and fermentation are particular procedures for meat flavour and also important for the releasing of bioactive peptides from parent proteins. Once being released, the peptides would play bioactive roles beyond their nutritional values. The physiological activities of meat‐derived peptides have been demonstrated to have antioxidative, antihypertensive, antimicrobial, opioid, antithrombotic and other bioactive effects. The regulation on immunological, gastrointestinal and neurological responses of those bioactive peptides supplies a vital base for the prevention of hypertension, obesity, diabetes and other metabolic disorders. In this review, we summarised the current studies on meat derived bioactive peptides along with their physiological functions to supply the overall understanding of the health benefit of bioactive peptides. [ABSTRACT FROM AUTHOR]

Highlights • Kefir milk is a probiotic beverage and its consumptions has several benefits. • Kefir treatment reduced the blood pressure in hypertensive animals. • Proteomic studies identified 35 potential ACE inhibitor peptides in this beverage. Abstract Kefir, a probiotic beverage prepared from fermented milk, has been associated with antihypertensive activity. However, the bioactive molecules responsible for this activity still remain unclear. Therefore, in this study we aim to evaluate the mechanisms of the antihypertensive effects of Kefir in the two-kidney one-clip hypertension model, and to bioprospect for bioactive peptides identified by proteomic methodologies. Treatment with Kefir was performed via gavage, and resulted in a 37 mmHg reduction in systolic arterial pressure and 19% inhibition of angiotensin converting enzyme (ACE) activity. For the proteopeptidomic study, the protein extract of Kefir beverage and non-fermented bovine milk were analysed by MALDI-TOF mass spectrometry, and their tryptic digestion products sequenced via Shotgun proteomics (Q-Exactive mass spectrometer). A list of 35 peptides with potential hypertensive activity due to ACE inhibition were identified. These results demonstrate the benefits of Kefir products, and may guide the design of new antihypertensive drugs. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Antihypertensive effect of Tianshu Capsule (TSC) is associated with vasorelaxation. • TSC-induced vasorelaxation via both endothelium-dependent and -independent pathway. • The NO/sGC/cGMP pathway, K+ and Ca2+ channels were involved in this vasorelaxation. Abstract Background Both Chuanxiong (Ligusticum chuanxiong Hort) and Tianma (Gastrodia elata Blume) have the effects of vasorelaxation and antihypertension. However, the effects of Tianshu Capsule (TSC, composed of Chuanxiong and Tianma in the mass ratio of 4:1) on antihypertensive activity have not been explored. This study aimed to investigate the eff ;ects of TSC on vascular tension and blood pressure in rats and to explore the underlying mechanisms. Methods The vasorelaxant effect of TSC was explored on thoracic aortic rings (both intact endothelium and denuded) preincubated with phenylephrine (Phe) or potassium chloride (KCL). The mechanism was investigated in the presence of antagonists or blockers on aorta isolated from normotensive rats. The in vivo antihypertensive effect was assessed using a tail-cuff method on spontaneously hypertensive rats (SHRs). Results TSC (0.125–4 mg/mL) produced a concentration-dependent vasorelaxation on aortic rings preincubated with Phe (1 μM) or KCL (60 mM). Removal of aorta endothelium markedly attenuated the TSC activity. Pretreatment of aortic rings with β-adrenoceptor blocker propranolol (1 μM), muscarinic receptor antagonist atropine (1 μM), cyclooxygenase inhibitor indomethacin (IDO, 1 μM), adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536, 100 μM), K+ channel blockers 4-aminopyridine(4-AP, 1 mM) or barium chloride(BaCl 2 , 1 mM) followed by addition of Phe (1 μM) prior to TSC did not influence the TSC-induced relaxation. In contrast, the vasorelaxant effects of TSC were markedly inhibited by the NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 10 μM), guanylyl cyclase inhibitor 1H- [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM), K+ channel blockers, glibenclamide (100 μM) and clotrimazole (5 mM). Moreover, TSC (2 mg/mL, 4 mg/mL) inhibited CaCl 2 -induced contractions and caused a concentration-dependent rightward shift of the response curves. Additionally, TSC (2 mg/mL, 4 mg/mL) depressed the constriction caused by Phe (1 μM) in the absence of extracellular Ca2+. Furthermore, TSC (2.15 g/kg) lowered the systolic blood pressure (SBP), with no alteration in heart rate (HR) in SHRs. Conclusions These findings demonstrated that TSC induced vasorelaxant effects via both endothelium-dependent and endothelium-independent pathways. The NO/sGC/cGMP pathway, ATP-sensitive K+ channels, Ca2+-activated K+ channels, inhibition of extracellular Ca2+ influx and intracellular Ca2+ release were probably involved in this relaxation. The vasorelaxant effects of TSC may make the greatest contribution to the reduction in high blood pressure. [ABSTRACT FROM AUTHOR]

Abstract In-vitro antidiabetic and antihypertensive properties of novel camel skin gelatin hydrolysates (CSGHs) were reported for the first time. Effect of different proteolytic enzymes, time of hydrolysis and enzyme: substrate (E/S) ratio on the bioactive (antidiabetic and antihypertensive) properties was explored. Results revealed that CSGHs exhibited highly potent inhibitory activity against dipeptidyl peptidase-IV (DPP-IV), pancreatic α-amylase (PA) and angiotensin-I converting enzyme (ACE) compared to non-hydrolyzed camel skin gelatin. All three enzyme combinations used produced highly potent PA inhibitory hydrolysates while for DPP-IV inhibitory property, protease and alcalase-protease (A/P) in combination produced more potent hydrolysates than alcalase generated hydrolysates. Moreover, alcalase and protease generated hydrolysates were highly active in inhibiting ACE activity in comparison to their combination (AP) (P < 0.05). Overall, no significant effect of E/S ratio and time of hydrolysis on production of DPP-IV, PA and ACE inhibitory peptides were observed. These findings suggest that both enzymes i.e. alcalase and protease alone or in combination were capable of producing camel skin gelatin hydrolysates with highly potent antidiabetic and antihypertensive properties. The present study presents the first report on the production of camel skin gelatin hydrolysates with strong in-vitro antidiabetic and antihypertensive potential. Future studies should be directed to identify the sequence of peptides responsibe for antidiabetic and antihypertensive activities. Highlights • Novel camel skin derived gelatin hydrolysates were produced. • ACE, DPP-IV and pancreatic α-amylase inhibition was reported by camel skin gelatin hydrolysates (CSGH) for the first time. • Protease enzyme was more effective than alcalase on DPP-IV inhibition. • Extending hydrolysis time beyond 2 h had very little effect on the ACE-IC50 values. [ABSTRACT FROM AUTHOR]

• Protein language model ESM-2 exhibited superiority over 12 popular peptide embedding methods. • The confident learning theory was first introduced to clean real-world biological data. • An ACE inhibitory peptide classifier, pLM4ACE, was developed with experimental data. • A user-friendly web server was built for practical usage of the advanced model. Angiotensin-I converting enzyme (ACE) regulates the renin-angiotensin system and is a drug target in clinical treatment for hypertension. This study aims to develop a protein language model (pLM) with evolutionary scale modeling (ESM-2) embeddings that is trained on experimental data to screen peptides with strong ACE inhibitory activity. Twelve conventional peptide embedding approaches and five machine learning (ML) modeling methods were also tested for performance comparison. Among the 65 classifiers tested, logistic regression with ESM-2 embeddings showed the best performance, with balanced accuracy (BACC), Matthews correlation coefficient (MCC), and area under the curve of 0.883 ± 0.017, 0.77 ± 0.032, and 0.96 ± 0.009, respectively. Multilayer perceptron and support vector machine also exhibited great compatibility with ESM-2 embeddings. The ESM-2 embeddings showed superior performance in enhancing the prediction model compared to the 12 traditional embedding methods. A user-friendly webserver (https://sqzujiduce.us-east-1.awsapprunner.com) with the top three models is now freely available. [ABSTRACT FROM AUTHOR]

Sensory evaluation is an important task for manufacturers to improve the product quality of new functional fermented milk drinks (FFMD) containing angiotensin‐converting enzyme inhibitory (ACE‐I) bioactive peptides produced during milk processing by enzymatic/mechanical hydrolysis. Herein, a fermented reconstituted skim milk (RSM) was made with Lactobacillus helveticus supplemented with Flavourzyme® using a bioreactor to improve cell viability and levels of ACE‐I bioactive peptides. Sensory evaluations of three different fermented RSM drink samples were conducted by 20 trained panellists. There were no significant differences in flavour, bitterns, appearance and acceptance of FFMD compared to the commercial product Yakult®. Addition of sucrose and flavour provided positive changes in terms of acceptability by consumers. [ABSTRACT FROM AUTHOR]

Angelica decursiva is a perennial herb that belongs to the Umbelliferae family. It is traditionally used to treat fever, upper respiratory tract infections, bleeding and hypertension. However, despite its extensive pharmacological potential, literature reports on its antihypertensive pharmacological properties are scarce. In the study, crude extract from A. decursiva roots was examined for its antihypertensive activity and its molecular basis was explored. A. decursiva roots were extracted with ethanol, and isolated with silica gel normal-phase chromatography and reverse-phase high performance liquid chromatography. L-NAME-induced hypertensive mouse model was used to detect in vivo hypertensive activity. Thoracic aorta ring contraction activity and electrophysiology recordings were employed to evaluate in vitro antihypertensive activity and revealed an antihypertensive target, which was transiently expressed in HEK293T cells. Angelica decursiva ethanol decoction (ADED) exhibited significant antihypertensive effects in L-NAME-induced hypertension models and phenylephrine-induced vasoconstriction. Further screening revealed that demethylsuberosin is an essential component accounting for the antihypertension effects of A. decursiva. Voltage-gated calcium channel Ca V 1.2 is the likely target of A. decursiva for its antihypertension effects. The study suggests that A. decursiva and demethylsuberosin may be effective antihypertensive agents in preclinical studies. It appears that A. decursiva and demethylsuberosin exert antihypertensive effects by inhibiting the Ca V 1.2 channel, which contributes to the vasodilatory effect. The present study provides experimental evidence that A. decursiva is an effective remedy for hypertension in folklore. Demethylsuberosin could be a lead molecule for antihypertension drug development. [Display omitted] • The study found that A. decursiva displayed antihypertensive properties. • A. decursiva active principles inhibit the Ca V 1.2 channel. • Demethylsuberosin is an essential component accounting for the antihypertension effects of A. decursiva. • Demethylsuberosin potently inhibits the Ca V 1.2 channel. [ABSTRACT FROM AUTHOR]

Background Angiotensin converting enzyme (ACE) is a key enzyme in the renin angiotensin system (RAS) responsible for conversion of angiotensin (Ang) I into Ang II, a vasoconstrictor leading to elevated blood pressure. ACE inhibitory (ACEi) peptides derived from food proteins have shown potential in the prevention and management of hypertension. Although most ACEi peptides were characterized based on in vitro ACEi activity, a relationship between ACE inhibition and physiological antihypertensive effect is not apparent, indicating the involvement of other mechanisms of action. Scope and approach This paper focuses on emerging antihypertensive mechanisms of ACEi peptides. As an alternate arm of the classic RAS, ACE2 cleaves Ang II into Ang (1–7) and thus counterbalances the harmful effects of Ang II. Endothelial dysfunction is now recognized as an early feature in the pathophysiology of metabolic syndrome and cardiovascular disorders including hypertension; endothelial dysfunction, vascular oxidative stress and inflammation are interplayed. Future perspectives on mechanistic study of ACEi peptides are forecasted. Key findings and conclusions Apart from classic ACE inhibition, emerging evidence suggests that food peptides can exert antihypertensive activity through upregulation of ACE2 (an ACE homologue that counterbalances the detrimental effect of elevated ACE), improvement of endothelial function, as well as reduced vascular oxidation and inflammation. Future research is expected to look into the effects of bioaccessibility, bioavailability, stability and reactivity of the peptides with food and gut matrices, as well as the gut microbiota, on blood pressure reduction. [ABSTRACT FROM AUTHOR]

In the present study, the effects of 6,6′-bieckol isolated from Ecklonia cava on angiotensin I-converting enzyme (ACE) inhibition and nitric oxide (NO) production, and the inhibitor’s binding modes using the crystal structure of ACE were examined. The effects of 6,6′-bieckol on systolic blood pressure (SBP) after meals were also investigated. We predicted the 3D structure of ACE and used a docking algorithm to understand the binding between ACE and 6,6′-bieckol. The molecular docking study revealed that ACE inhibitory activity of 6,6′-bieckol was mainly attributed to the hydrogen bond interactions (Lys454, His353, Glu162, Glu376, Glu384 and Glu411) and Pi interactions (Lys511 and His513) between ACE and 6,6′-bieckol. 6,6′-bieckol significantly increased the production of nitric oxide (NO) and by phosphorylating endothelial nitric oxide synthase (eNOS) in human endothelial cells. Furthermore, antihypertensive effect in spontaneously hypertensive rats (SHRs) also revealed that oral administration of the compound can down-regulate (28.6 mmHg in 6 h) systolic blood pressure (SBP). [ABSTRACT FROM AUTHOR]

S-1-propenyl-L-cysteine (S1PC) is a stereoisomer of S-allyl-L-cysteine (SAC), an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE). The existence of S1PC in garlic preparations has been known since the 1960's. However, there was no report regarding the biological and/or pharmacological activity of S1PC until 2016. Recently, we performed a series of studies to examine the chemical, biological, pharmacological and pharmacokinetic properties of S1PC, and obtained some interesting results. S1PC existed only in trace amounts in raw garlic, but its concentration increased almost up to the level similar of SAC through aging process of AGE. S1PC showed immunomodulatory effects in vitro and in vivo, and reduced blood pressure in a hypertensive animal model. A pharmacokinetic study revealed that S1PC was readily absorbed after oral administration in rats and dogs with bioavailability of 88-100%. Additionally, S1PC had little inhibitory influence on human cytochrome P450 activities, even at a concentration of 1 mM. Based on these findings, S1PC was suggested to be another important pharmacologically active and safe component of AGE similar to SAC. In this review, we highlight some results from recent studies on S1PC and discuss the potential medicinal value of S1PC. [ABSTRACT FROM AUTHOR]

Recently, a new syndromic disease combination theory of traditional Chinese medicine (TCM) for hypertensive treatment has been introduced. In the wake of this new concept, a new science-based TCM formula that counteracts various syndromes is needed. The objective of this study was to develop such a formula. Five of the most clinically prescribed TCM herbs that work on different syndromes, namely Gastrodia elata, Uncaria rhynchophylla, Pueraria thomsonii, Panax notoginseng, and Alisma orientale, were selected for this study. The fingerprints of these five herbs were analyzed by tri-step Fourier transform infrared spectroscopy. Three different solvents, 95% ethanol, 50% ethanol, and distilled water, were used for the maceration of the herbs and their vasodilatory effects were studied using in vitro precontracted aortic ring model. Among these, the 50% ethanolic extracts of G. elata (GE50) and A. orientale (AO50), and 95% ethanolic extracts of U. rhynchophylla (UR95), P. thomsonii (PT95), and P. notoginseng (PN95) were found to be the most effective for eliciting vasodilation. Thus, these five extracts were used for orthogonal stimulus-response compatibility group studies by using L25 (55) formula. The best combination ratio for GE50, UR95, PT95, PN95, and AO50, which was assigned as Formula 1 (F1), was found at EC0, EC25, EC20, EC20, and EC10, respectively. The vasodilatory effect of the extracts prepared from different extraction methods using F1 ratio was also studied. From the results, the EC50 and Rmax of total 50% ethanolic extract of five herbs using F1 ratio (F1-2) were 0.028 ± 0.005 mg/mL and 101.71% ± 3.64%, with better values than F1 (0.104 ± 0.014 mg/mL and 97.80% ± 3.12%, respectively). In conclusion, the optimum ratio and appropriate extraction method (F1-2) for the new TCM formula were revealed. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is a leading problem in Indonesia, because of the high prevalence and the long term effect. Bitter melon leaves (Momordica charantia L.) has been traditionally utilized to treat hypertension, yet not many studies explained the antihypertension effect of this plant. Methods: This study was conducted to test the benefit of bitter melon leaves as antihypertension using angiotensin converting enzyme inhibition activity in 80% ethanolic extract and its fractions (n-hexane, ethyl acetate, and n-butanol) using ACE kit-WST (Dojindo, Japan). Then the antihypertension activity was associated with the phenolic content which was expressed in gallic acid equivalent (GAE) and total flavonoid in quercetin equivalent (QE). Results: Result of the study showed that the IC50 value obtained from the ethanolic extract to inhibit ACE activity was 7.52 μg/mL and the highest inhibition obtained in ethyl acetate fraction with IC50 value was 4,29 μg/mL. Phenolic total and flavonoid total determination also showed that the highest content obtained in ethyl acetate fraction with 18.752 mg GAE/gr extract and 8.310 mg QE/gr extract, respectively. Conclusion: According to the study, it could be concluded that bitter melon (Momordica charantia L.) leaves provide inhibition activity against Angiotensin Converting Enzyme (ACE) and chemical compounds that were expected to play an active role in inhibiting ACE were flavonoid and tannin. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the antioxidative activities of Crab meat analogue prepared with protein hydrolysates obtained from mechanically deboned chicken meat (MDCM) from spent laying hens. 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) radical-scavenging activity was increased by adding MDCM hydrolysates during storage, and activity correlated with the concentration of DPPH added up to 6 weeks of storage. Hydroxyl radical-scavenging activity was increased in all analogues containing MDCM hydrolysates. At 0 days of storage, angiotensin I-converting enzyme (ACE)-inhibitory activity was increased by the addition of MDCM hydrolysates. Activity did not correlate after 6 weeks of storage, in which ACE-inhibitory activity was increased with low concentrations of MDCM hydrolysates, but no ACE-inhibitory activity was observed at higher concentrations. The liverprotecting activity of crab meat analogue was shown to be around 60% of the positive control; however, it was not significantly different among the samples during storage. These results support the use of MDCM as a source of health-promoting constituents in crab meat analogue. [ABSTRACT FROM AUTHOR]

Angiotensin- I- converting enzyme (ACE) is crucial in the control of hypertension and the development of type- 2 diabetes and other diseases associated with metabolic syndrome. The aim of this work was to utilize Pacific cod skin to purify ACE inhibitory peptides. First, gelatin was extracted from Pacific cod skin and hydrolyzed with several enzymes (pepsin, papain, α-chymotrypsin, trypsin, neutrase, and alcalase). The pepsin hydrolysate showed the strongest ACE inhibitory effect and was further fractionated into different ranges of molecular weight (<1, 1–5, 5–10, and >10 kDa) using ultrafiltration (UF) membranes. The peptic hydrolysate below 1 kDa resulted in two potent ACE inhibitory peptides, GASSGMPG (662 Da) and LAYA (436 Da), with IC 50 values (concentration required to decrease the ACE activity by 50%) of 6.9 and 14.5 μM, respectively. Moreover, to explore the interaction between the peptides and ACE molecule, the tertiary structure of ACE and docking simulation to the peptides were predicted using Docking Server. Pacific cod peptides can be used as functional food ingredients to prevent hypertension and its related diseases. [ABSTRACT FROM AUTHOR]

A series of new 5-oxo-1,2,4-oxadiazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole group was designed, synthesized, and pharmacologically evaluated. These derivatives displayed high affinities to the AT1receptor at the same order of magnitude to losartan. The methyl ester with 1, 4-disubsituted indole group, 1 (5.01 ± 1.67 nM) showed high antihypertension activity on spontaneously hypertensive rats (SHRs). Its maximal response lowered 30 mmHg of mean blood pressure (MBP) at 10 mg/kg after oral administration, which was better than irbesartan, and the antihypertensive effect lasted beyond 24 h. These results made 1 deserve further investigation. [ABSTRACT FROM AUTHOR]

Objectives This study investigated the effect of tannic acid ( TA), a plant-derived hydrolyzable polyphenol, on Kv7.4 and Kv7.5 K+ channels and rat mesenteric artery. Methods Whole-cell patch clamp experiments were used to record the Kv7.4 and Kv7.3/7.5 K+ currents expressed in HEK293 cells; and the tension changes of mesenteric arteries isolated from rats were recorded using small vessel myography apparatus. Key findings Tannic acid increases the Kv7.4 and Kv7.3/7.5 K+ currents in a concentration-dependent manner (median effective concentration ( EC50) = 27.3 ± 3.6 μ m and EC50 = 23.1 ± 3.9 μ m, respectively). In addition, 30 μ m TA shifts the G- V curve of Kv7.4 and Kv7.3/7.5 K+ currents to the left by 14.18 and 25.24 mV, respectively, and prolongs the deactivation time constants by 184.44 and 154.77 ms, respectively. Moreover, TA relaxes the vascular tension of rat mesenteric arteries in a concentration-dependent manner (half inhibitory concentration ( IC50) = 148.7 ± 13.4 μ m). Conclusion These results confirms the vasodilatory effects of TA on rat mesenteric artery and the activating effects on the Kv7.4 and Kv7.3/7.5 K+ channels, which may be a mechanism to explain the vasodilatory effect and this mechanism can be used in the research of antihypertension. [ABSTRACT FROM AUTHOR]

2-Benzylisoquinolin-1(2 H )-ones has been proposed as vasodilative agents on the basis of scaffold hopping. In the present study, a series of 2-benzylisoquinolin-1(2 H )-ones were synthesized. Their vasodilative effects were evaluated by wire myograph on isolated rat mesenteric arterial ring induced contraction with 60 mM KCl. The structure–activity relationships of target compounds were discussed. Among these compounds, C7 and C8 displayed potent vasodilative effects and significantly inhibited the contraction of rat mesenteric arterial rings induced by phenylephrine. The antihypertensive effects of compounds C7 and C8 on SHR were further evaluated. The results indicated that oral administrational C7 and C8 can significantly reduce both diastolic and systolic blood pressure in a dose-dependent manner. Moreover, C7 maintained the effects for 4 h at a dosage of 4.0 mg/kg. These findings suggest that the title compounds can serve as novel vasodilative agents and promising antihypertensive agents. [ABSTRACT FROM AUTHOR]

This study was aimed to generate a valuable protein hydrolysate and bioactive peptides with strong ACE-inhibitory activity in vitro and in vivo from palm kernel cake (PKC) protein. PKC protein was independently hydrolyzed by seven different proteases to produce PKC protein hydrolysates. Among those investigated, papain-produced hydrolysate revealed the highest ACE-inhibitory activity (70.9%). When normotensive rats induced with hypertension were fed the hydrolysate at a dose of 75 mg/kg body weight, their blood pressures stabilized considerably. Fractionation of the protein hydrolysate using RP-HPLC revealed a direct relationship between hydrophobicity and ACE-inhibitory activity. The fractions with relatively higher ACE-inhibitory activity were further fractionated by isoelectric focusing, out of which fractions having neutral and basic charges showing higher ACE-inhibitory activities (77% and 75%, respectively). Nine peptide sequences were identified by Q-TOF mass spectrometry, and their respective ACE-inhibitory activities evaluated. The peptide sequences YLLLK, YGIKVGYAIP, and LPWRPATNVF showed ACE-inhibitory activities of 100%; however, the best IC 50 values were observed for YGIKVGYAIP, GIFE and LPWRPATNVF at 1 μM, 3 μM and 20 μM, respectively. [ABSTRACT FROM AUTHOR]

Inhibition of angiotensin-converting enzyme I (ACE-I) in vitro and in vivo from peptide fractions by enzymatic hydrolysis of the Vigna unguiculata protein concentrate was evaluated. Hydrolysis was done with Pepsin-Pancreatin and Flavourzima in two separate systems. The resulting hidrolysates were ultrafiltrated to obtain fractions with different molecular weight. The fractions with better inhibition Flavourzima were size > 1 kDa (> 1 kDa-F) and < 1 kDa (< 1 kDa-F), with an IC50 of 1222.84 and 1098.6 μg/ml respectively. Pepsin-Pancreatin fraction. [ABSTRACT FROM AUTHOR]

To exploit the S3′ subsite of renin active site for renin inhibitor design, 42 aliskiren derivatives with modified P2′ portion were designed, synthesized and biologically evaluated. Some highly potent renin inhibitors (IC 50 < 3 nM) were identified, among which compounds 38 (IC 50 = 0.9 nM) and 39 (IC 50 = 0.7 nM) were over 2.5-fold more potent than aliskiren (IC 50 = 2.3 nM). SAR analysis indicated that incorporation of polar hydrophilic moieties into the P2′ portion of renin inhibitors generally enhanced the potency. Consistently with this, molecular modeling study revealed that the triazole part of 39 could provide additional interactions to the S3′ subsite of renin active site. Moreover, in vivo evaluation in the double transgenic mouse hypertension model demonstrated that 39 produced greater reduction of the mean arterial blood pressure than ariskiren at the doses of 17.0 and 34.0 μmol/kg, respectively. Taken together, the S3′ subsite of renin active site merits further consideration for renin inhibitor design. [ABSTRACT FROM AUTHOR]

Novel angiotensin II receptor type 1 (AT 1 ) blockers bearing 6-substituted carbamoyl benzimidazoles with a chiral center were designed and synthesized as the first step to develop new antihypertensive agents and understand their pharmacodynamic and pharmacokinetic properties. The newly synthesized compounds were tested for their potential ability to displace [ 125 I] Sar 1 Ile 8 -Ang II, which was specifically bound to human AT 1 receptor. Radioligand binding assays revealed nanomolar affinity in several compounds under study. The IC 50 values of nine ligands were higher than those of Losartan. The screening of decreased blood pressure in spontaneous hypertensive rats displayed that compound 8S (IC 50 = 5.0 nM) was equipotent with Losartan, whereas compounds 13R (IC 50 = 7.3 nM), 14R (IC 50 = 6.3 nM), and 14S (IC 50 = 3.5 nM) were slightly ahead of Losartan, and the most significant activity was demonstrated by compound 8R (IC 50 = 1.1 nM). Candidate 8R was identified for its excellent efficacy in antihypertension and fairly low toxicity based on plasma analyses, toxicology studies, and chronic oral tests. Finally, compound 8R exhibited strong and multiple interactions with target active sites of the theoretical AT 1 receptor model in docking study. [ABSTRACT FROM AUTHOR]

Two series of novel NO-releasing benzimidazole derivatives ( 8a- e, 9a- g) were designed and synthesized by coupling nitro ester and furoxan NO-donor moieties with benzimidazole biphenyl skeleton. The NO-releasing assay indicated that all the target compounds had different level of NO-releasing ability. Furthermore, the isolated organ assay (rat aortic strips) was used to evaluate the antagonism of Ang II-induced vasoconstriction ability. It was observed that the pA2 values of compounds 8e and 9e were better than that of lead compound 6. Moreover, the pharmacological investigation showed that the antagonism of Ang II-induced pressure response by oral administration of compound 8e was obviously superior to that of lead compound 6, and comparable to that of the positive control losartan. These results suggested that NO-releasing hybrids may provide a promising approach for the discovery of novel antihypertensive agents. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate antihypertensive effect of bioactive peptides from skate ( Okamejei kenojei ) skin gelatin. The Alcalase/protease gelatin hydrolysate below 1 kDa (SAP) exhibited the highest angiotensin-I converting enzyme (ACE) inhibition compared to other hydrolysates. SAP can decrease systolic blood pressure significantly in spontaneously hypertensive rats. SAP inhibited vasoconstriction via PPAR-γ expression, activation and phosphorylation of eNOS in lungs. Moreover, the expression levels of endothelin-1, RhoA, α-smooth muscle actin, cleaved caspase 3 and MAPK were decreased by SAP in lungs. Vascularity, muscularization and cellular proliferation in lungs were detected by immunohistochemical staining. Finally, two purified peptides (LGPLGHQ, 720 Da and MVGSAPGVL, 829 Da) showed potent ACE inhibition with IC 50 values of 4.22 and 3.09 μM, respectively. These results indicate that bioactive peptides isolated from skate skin gelatin may serve as candidates against hypertension and could be used as functional food ingredients. [ABSTRACT FROM AUTHOR]

Background: Visit-to-visit variability in blood pressure (BP) was demonstrated to correlate with cardiovascular events independent of mean BP. The goal of the present study was to investigate the correlation of visit-to-visit BP variability with artery stiffness and myocardial perfusion in on-treated hypertensive patients. Methods: BP was measured in 271 hypertensive patients at every visit over the course of the antihypertensive treatment, and the standard deviation (SD), coefficient of variation (CV), maximum, and minimum in serial BP were calculated. Non-invasive pulse wave analysis was performed in all patients. Results: Compared with baseline, carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (Aix) and Aix adjusted to a 'standard heart rate' of 75 beats/min (Aix@HR75) were markedly declined, and sub-endocardial viability ratio (SEVR) was obviously increased in each group ( p < 0.001). The changes of cfPWV, SEVR, Aix and Aix@HR75 in patients with lower SD of systolic blood pressure (SBP) were significantly greater than those in patients with higher SD of SBP. And the changes were statistically correlated with both SD and CV of serial SBP during follow-up, even after adjusted for mean SBP and mean diastolic blood pressure (DBP). Conclusion: Visit-to-visit SBP variability is independently correlated with changes of artery stiffness and myocardial perfusion in on-treated hypertensive patients. [ABSTRACT FROM AUTHOR]

Abstract: One of the main pathological changes of hypertension is the dysfunction of blood vessels. We have found in our previous study that formononetin, one kind of phytoestrogens, has an acute antihypertensive effect. Therefore, we hypothesized that formononetin might produce a chronic antihypertensive effect through regulating the expressions of contractile receptors and endothelial nitric oxide synthase (eNOS) in artery. The present study was conducted to verify this effect. Male spontaneously hypertensive rats (SHRs) were divided into two groups, orally administrated formononetin (50mg/kg per day) and Tween 80 vehicle, respectively, for 8 weeks. The blood pressure was measured by tail-cuff method. Isometric tension of arterial rings was recorded by a myograph system. The mRNA and protein expression in arteries was determined with quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Results showed that the systolic blood pressure of SHRs decreased significantly in formononetin group compared to Tween 80 group. The vasoconstriction induced by phenylephrine or 5-hydroxytryptamine (5-HT) in the mesenteric artery segments in formononetin group was decreased, and the relaxation induced by acetylcholine was increased compared with that in Tween 80 group. In the mesenteric arteries of the formononetin-treated SHRs, the expressions of α1-adrenoceptors and 5-HT2A/1B receptors at both mRNA and protein levels decreased, while the mRNA and protein expressions of eNOS increased. In conclusion, formononetin has a chronic antihypertensive effect in SHRs. The antihypertensive mechanism may be associated with the down-regulation of α1-adrenoceptors and 5-HT2A/1B receptors, and the up-regulation of eNOS expression in arteries. [Copyright &y& Elsevier]

Abstract: The influence of polymerisation (number of subunits), galloylation (content of esterified gallates) and type of subunit in the polymeric chain of proanthocyanidins (PAs) in skin and seed extracts of Vitis vinífera L. cv. País on the inhibition of angiotensin I-converting enzyme (ACE) was evaluated. Gel permeation chromatography was used to purify the extracts, which were characterised by acid-catalysis depolymerisation followed by HPLC. ACE activity was tested by quantitative HPLC, measuring the hippuric acid (HA) produced from hippuryl-l-histidyl-l-leucine (HHL) hydrolysis by ACE. The inhibitory activity on ACE was verified for all the obtained fractions, although the PAs’ molecular size and structural composition affected the ACE inhibition. The higher inhibitory power of skin extract was associated with greater –OH availability, higher mean degree of polymerisation (mDP) and the presence of epicatechin-gallate (ECG) expressed as percentage of galloylation (%G). However, comparing only the structural composition (for samples with similar mDP), % epicatechin (EC) and ECG, <3 %G appeared to be the most important characteristic when considering inhibitory effect of both tissues. Thus, these results indicate that the ACE inhibition by grape PAs depend on the stereochemical configuration of the studied flavanols. [Copyright &y& Elsevier]

Abstract: We hypothesised that mulberry leaves (ML) exert their antihypertensive effect through γ-aminobutyric acid (GABA) and that the antihypertensive activity of ML extract would be comparable to GABA alone in spontaneously hypertensive rats (SHR). We found that single administration of a water extract from leaves of Morus alba L. (WEML) lowered systolic blood pressure (SBP) transiently in a dose-dependent manner. Interestingly, the SBP-lowering effect of WEML was significantly higher than after treatment with GABA alone. We further found that WEML strongly inhibited angiotensin I-converting enzyme (ACE) activity in vitro with an IC50 value of 29.8mg/ml. These results suggest that WEML has a transient antihypertensive effect in vivo that may involve a mechanism of ACE inhibition in addition to GABA. [Copyright &y& Elsevier]

Abstract: Gelatin extracted from squid (Dosidicus eschrichitii Steenstrup) skin was hydrolysed with pepsin to prepare Angiotensin-I-Converting Enzyme (ACE) inhibitory peptide. The ACE-inhibitory activity was measured by spectrophotometric assay. The hydrolysate was fractionated into three ranges of molecular weight (6kDa

The purpose of this study was to evaluate the effects of SM-368229, a novel mineralocorticoid receptor (MR) antagonist, on the blood pressure and cardiorenal injury markers in aldosterone/salt-treated hypertensive rats, in comparison to those of spironolactone (SPI). Uninephrectomized rats, given 1% NaCl to drink, were infused with aldosterone (0.75 μg/h, s.c.). In experiment 1, SM-368229 (10, 30 mg/kg) or SPI (100 mg/kg) were administered for 14 days immediately after aldosterone/salt loading. In experiment 2, SM-368229 (10 mg/kg) or SPI (100 mg/kg) were administered for 10 days after 10 days of aldosterone/salt loading. In both experiments, SM-368229 prevented the increase in systolic blood pressure, heart/kidney weights, and urinary protein/N-acetyl-β-D- glucosaminidase excretion caused by aldosterone infusion. In real-time polymerase chain reaction analysis, SM-368229 abolished aldosterone-induced gene expression levels for inflammatory, fibrosis and oxidative stress markers in hearts and kidneys. The antihypertensive effect of SM-368229 (30 mg/kg) was superior to that of SPI, and the antihypertensive and cardiorenal protective effects of SM-368229 (10 mg/kg) were similar to those of SPI (100 mg/kg) in both experiments. These results clearly demonstrated that SM-368229 strongly attenuated the progression of hypertension and exerted cardiorenal protection in aldosterone/salt-treated hypertensive rats. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]