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]

Integrated bioinformatics tools have created more efficient and robust methods to overcome in vitro challenges and have been widely utilized for the investigation of food proteins and the generation of peptide sequences. This study aimed to analyze the physicochemical properties and bioactivities of novel peptides derived from hydrolyzed milkfish (Chanos chanos) protein sequences and to discover their potential angiotensin-converting enzyme (ACE)- and dipeptidyl peptidase-4 (DPPIV)-inhibitory activities using machine learning-based tools, including BIOPEP-UWM, PeptideRanker, and the molecular docking software HADDOCK 2.4. Nine and three peptides were predicted to have ACE- and DPPIV-inhibitory activities, respectively. The DPPIV-inhibitory peptides were predicted to inhibit the compound with no known specific mode. Meanwhile, two tetrapeptides (MVWH and PPPS) were predicted to possess a competitive mode of ACE inhibition by directly binding to the tetra-coordinated Zn ion. Among all nine discovered ACE-inhibitory peptides, only the PPPS peptide satisfied the drug-likeness analysis requirements with no violations of the Lipinski rule of five and should be further investigated in vitro. [ABSTRACT FROM AUTHOR]

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

Abstract The homeostasis of the gut microbiota is a crucial factor in regulating peripheral and central blood pressure. Formulating a food-derived mixture of antioxidants, anti-inflammatory compounds and prebiotics to maintain the homeostasis of the gut microbiota will be essential for preventing and alleviating hypertension. Although bioactive peptides and plant extracts have been demonstrated not only to be excellent antioxidants and anti-inflammatory agents but also to promote the homeostasis of the microbiota, few studies have investigated the influence of multiple peptides mixed with plant extracts on the gut microbiota of hypertensive rats. This is the first study to characterize the fecal microbiome of spontaneously hypertensive rats supplemented with a mixture of multiple peptides and plant extracts by integrating 16 S rRNA gene sequencing. During the six-week experiment, the animals were healthy and without mortality. The results revealed that oral supplementation with the formulation reduced both systolic and diastolic blood pressure, improved the gut microbiota by increasing the ratio of Bacteroidetes to Firmicutes, and increased the relative abundance of specific genera, such as Lactobacillus. This study suggested that a synergistic formulation of multiple peptides mixed with plant extracts could be a novel strategy for preventing and alleviating hypertensive diseases. Graphical Abstract

The homeostasis of the gut microbiota is a crucial factor in regulating peripheral and central blood pressure. Formulating a food-derived mixture of antioxidants, anti-inflammatory compounds and prebiotics to maintain the homeostasis of the gut microbiota will be essential for preventing and alleviating hypertension. Although bioactive peptides and plant extracts have been demonstrated not only to be excellent antioxidants and anti-inflammatory agents but also to promote the homeostasis of the microbiota, few studies have investigated the influence of multiple peptides mixed with plant extracts on the gut microbiota of hypertensive rats. This is the first study to characterize the fecal microbiome of spontaneously hypertensive rats supplemented with a mixture of multiple peptides and plant extracts by integrating 16 S rRNA gene sequencing. During the six-week experiment, the animals were healthy and without mortality. The results revealed that oral supplementation with the formulation reduced both systolic and diastolic blood pressure, improved the gut microbiota by increasing the ratio of Bacteroidetes to Firmicutes, and increased the relative abundance of specific genera, such as Lactobacillus. This study suggested that a synergistic formulation of multiple peptides mixed with plant extracts could be a novel strategy for preventing and alleviating hypertensive diseases. [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]

Over the years, isolated compounds from medicinal plants have been lead candidates in drug discovery and they are useful therapeutic aid to patients. This work isolated a compound from the seed of Parinari curatellifolia and investigated its inhibitory potential and mechanism on angiotensin-1-converting enzyme (ACE1). The methanolic extract of the seed was subjected to chromatographic techniques and yielded a white, crystalline solid. Structural elucidation of the compound was carried out using NMR and MS spectroscopic techniques. The use of N-(3-[2- furyl-acryloyl]-Phe-Gly-Gly) (FAPGG) as an enzyme substrate and the Michealis-Menten method in this study showed how sensitive and fast ACE1 could be inhibited. Inhibition mechanism was explored using the Lineweaver-Burk model, and IC50 was determined using Cheng-Prusoff empirical analysis. Molecular interaction with ACE1 was investigated computationally. NMR and MS spectroscopy showed the compound to be Akuammine, with 26 protons, 22 carbons, 2 nitrogen, and 4 oxygen atoms and chlorinated molecular ion peak at m/z 417.1593. Akuammine exhibited an IC50 of 8.5 µM and displayed mixed type inhibition. Molecular dynamics simulations indicated strong interaction at the allosteric site of ACE1, primarily through hydrophobic interactions. Akuammine demonstrated an ability as a template for antihypertensive agent. This ability may contribute to the ethno botanical uses of Parinari curatellifolia seed. [ABSTRACT FROM AUTHOR]

Fekade Beshah Tessema,1,2 Yilma Hunde Gonfa,2,3 Tilahun Belayneh Asfaw,4 Mesfin Getachew Tadesse,2,5 Rakesh Kumar Bachheti2,6 1Department of Chemistry, College of Natural and Computational Science, Woldia University, Woldia, Ethiopia; 2Department of Industrial Chemistry, College of Natural and Applied Sciences, Addis Ababa Science and Technology University, Addis Ababa, Ethiopia; 3Department of Chemistry, College of Natural and Computational Science, Ambo University, Ambo, Ethiopia; 4Department of Chemistry, College of Natural and Computational Science, Gondar University, Gondar, Ethiopia; 5Centre of Excellence in Biotechnology and Bioprocess, Addis Ababa Science and Technology University, Addis Ababa, Ethiopia; 6Department of Allied Sciences, Graphic Era Hill University, Society Area, Clement Town, Dehradun, 248002, IndiaCorrespondence: Fekade Beshah Tessema, Tel +251913141754, Email fbms08@gmail.comBackground: Ajuga integrifolia (Armagusa) is used as a decoction to treat high blood pressure and diabetes, widely in Ethiopia. Specific compounds for anti-hypertension activity were not identified so far. This study aims to provide a scientific basis for the therapeutic use of A. integrifolia as an antihypertension agent.Methods: In silico studies were used to evaluate the antihypertensive components of A. integrifolia. Flavonoids identified using HPLC analysis and iridoid glycosides isolated from A. integrifolia in this study and those isolated from synonyms (A. remota and A. bractosa) were considered in the molecular docking study. Interactions were studied by using Autodock vina (1.2) on PyRx 0.8 and visualizing in 2D and 3D using ligPlot+ and Discovery studio software. Activities like vasoprotection and druglikeness properties were predicted using online servers.Results: Flavonoids such as quercetin, myricetin, and rutin were identified and quantified by HPLC analysis from different extracts of A. integrifolia. Reptoside and 8-O-acetylharpgide isolated from the aerial part of A. integrifolia. The binding energies of all 17 candidates considered in this study range from − 10.2 kcal/mol to − 7.5 kcal/mol and are lower than enalapril (reference drug: − 5.9 kcal/mol). The binding energies, in most case, constitute hydrogen bonding. Biological activity predicted using PASS test also showed that the flavonoids have more probability of activity than the iridoid glycosides. Druglikeness properties of the candidate molecules showed that most follow the Lipinski rule of five with few violations.Conclusion: Lower binding energies involving hydrogen bonding and predicted activities concerning hypertension confirm the traditional use of the aerial part of the medicinal plant concerned. Flavonoids: rutin, myricetin, quercetin, and kaempferol take the leading role in the antihypertensive activity of the aerial part of A. integrifolia. The iridoid glycosides studied are almost similar in their effect on their antihypertensive activity and still better than the reference drug.Keywords: A. integrifolia, antihypertension, flavonoids, iridoid glycosides

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]

Integrated bioinformatics tools have created more efficient and robust methods to overcome in vitro challenges and have been widely utilized for the investigation of food proteins and the generation of peptide sequences. This study aimed to analyze the physicochemical properties and bioactivities of novel peptides derived from hydrolyzed milkfish (Chanos chanos) protein sequences and to discover their potential angiotensin-converting enzyme (ACE)- and dipeptidyl peptidase-4 (DPPIV)-inhibitory activities using machine learning-based tools, including BIOPEP-UWM, PeptideRanker, and the molecular docking software HADDOCK 2.4. Nine and three peptides were predicted to have ACE- and DPPIV-inhibitory activities, respectively. The DPPIV-inhibitory peptides were predicted to inhibit the compound with no known specific mode. Meanwhile, two tetrapeptides (MVWH and PPPS) were predicted to possess a competitive mode of ACE inhibition by directly binding to the tetra-coordinated Zn ion. Among all nine discovered ACE-inhibitory peptides, only the PPPS peptide satisfied the drug-likeness analysis requirements with no violations of the Lipinski rule of five and should be further investigated in vitro.

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]

Preeclampsia is one of many unsolved obstetric problems. The purpose of this research is to compare effectiveness of antihypertensive in preeclampsia patient in RSUD Panembahan Senopati Bantul in the period January-July 2019. This study needs to analyze about antihypertensive drugs in preeclampsia because Preeclampsia is the 3rd rank of disease in pregnancy that causes maternal death after hemorrhagic and cardiovascular diseases. The study was conducted at Panembahan Senopati Hospital Bantul because hypertension in inpatient was ranked first in 10 distributions of noncommunicable diseases. The research was observational analytic using a cross sectional study with retrospective data collection of patient medical record. Samples were selected on inclusion and exclusion criteria in 46 cases. Data analysis using Mann-Whitney to determine differences in drug effectiveness and Fisher's to determine the relationship. The results are found that no relationship between maternal age, obstetrical age, pregnancy status, method of birth, and length of stay, but there was a relationship between the severity of preeclampsia with the achievement of blood pressure targets. The results of comparative analysis of the effectiveness nifedipine monotherapy with combination of nifedipine + methyldopa there was a significant difference (p = 0.006), and there was a significant relationship between nifedipine monotherapy and combination of nifedipine + methyldopa (p = 0.015) OR results = 7.200. The conclusion of this study is more effective to use the combination of nifedipine + methyldopa for patients with preeclampsia.

Background Avocado leaves ( Persea americana Mill.) have been traditionally used as antihypertensive. Various studies have tested the benefits of the Persea americana Mill. in treating hypertension but still using extracts not yet using nanoparticles. Therefore, this study aims to study the effectiveness of avocado leaf extract, including the nanoparticles, on salt-induced hypertensive Wistar rats in inhibiting the ACE enzyme, which causes decreasing systolic blood pressure (SBP) and diastolic blood pressure (DBP) as well as increasing urine volume. Methods This study used an experimental in vivo study design involving 24 white male Wistar rats ( Rattus norvegicus), aged 2–3 months, weighing 130–250 g, and of a healthy condition with active movement. The samples were randomly divided into six treatment groups and post-test only research design with control group design. Results The result of the study showed that the extract contained a quercetin of 1129.597 ppm and 10 mineral compounds, including potassium, with the highest content. The analysis of antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl method showed that the antioxidant activity at IC 50 was 44.734 ppm. The P. americana leaf extract nanoparticles had the most significant result in reducing blood pressure in Wistar rats induced by 16% NaCl for 14 days SBP to normal was by 68.75 mmHg (175.00±21.57 mmHg to 106.25±9.21 mmHg) and 55.25 mmHg (128.42±25.75 mmHg to 73.17±15.75 mmHg), respectively. Also, avocado leaf extract caused the decrease of SBP from 164.92±7.16 mmHg to 116.83±6.36 mmHg and DBP from 118.42±16.24 mmHg to 82.83±6.47 mmHg. The P. americana leaf extract nanoparticles resulted in the most urine volume at 13.5 ml, with the highest DAI value of 2.25. The ACE inhibitor test using the ELISA method showed that the P. americana leaf extract and the nanoparticle extract inhibition against the ACE enzyme were 60.0±12.1 % and 59.5±3%, respectively. The mean serum nitrate as a result of P. americana leaf extract (K4) and nanoparticles of P. americana leaf extract (K5) were 44.0±9.0 μmol/L and 41.1±11.5 μmol/L, respectively. The mean of serum nitrite was led by P. americana leaf extract (K4), and nanoparticles of P. americana leaf extract (K5) were 83.7±24.0 μmol/L and 81.0±23.2 μmol/L, sequentially. Conclusions The study showed that the leaf extract and nanoparticle extract of Persea americana Mill. was effective as an antihypertensive.

Processing can change the properties and flavors of food. Many plants in the Araceae family can be used as food or medicine, but their raw materials are usually toxic, such as Pinellia ternata tuber (PTT). After processing (processed PTT, PPTT), its toxicity is reduced. However, the mechanism remains unclear. In this study, a novel approach integrating liquid chromatography-mass spectrometry, feature-based molecular networking (FBMN), de novo sequencing, and protein database searching was applied to rapidly discover and characterize peptides in PPTT. Potential antihypertensive peptides were screened using in silico methods, angiotensin I-converting enzyme (ACE) inhibitory assay, and molecular docking analysis. A significant decrease was observed in toxic lectins after processing. Meanwhile, a total of 1954 mass spectral nodes were discovered in PPTT, of which 130 were annotated as peptides by FBMN. These peptides, ranging from 2 to 21 amino acids, were rapidly identified using PEAKS. Notably, 98 peptides were derived from lectins, most of which increased after processing. Approximately 30% of identified peptides were screened for potential high antihypertensive activity in silico. Five peptides exhibited inhibitory effects on ACE, with two showing IC50 values of 131 and 185 μM. Dynamic profiling indicated that 7–9 days of processing is optimal for reducing toxicity and enhancing efficacy. More importantly, these peptides were also found in commercial PPTT, confirming their bioactivity contributions. These findings provide insights into the mechanism by which food processing drives the toxic lectin reduction and bioactive peptide enhancement in PTT, providing a novel approach to rapidly discover bioactive peptides, which can be extended to other foods in Araceae family.

Sweet potato is a rich source of antioxidant phytohemicals, like β-carotene, vitamin C, anthocyanins, xanthophylls, and phenolics, which are relevant for providing dietary protections against chronic oxidative stress-associated diseases, like type 2 diabetes. However, the health protective phytochemical profiles and associated antioxidant and anti-diabetic properties of sweet potatoes vary widely between different flesh color and among cultivars. Therefore, the aim of this study was to screen aqueous and ethanol (12%) extracts of seven sweet potato cultivars with different flesh colors (white–yellow, orange, and purple) for their phenolic phytochemical-linked functional qualities. Total soluble phenolic (TSP) content, phenolic profile, protein content, total antioxidant activity, anti-hyperglycemic function relevant α-amylase, α-glucosidase, and anti-hypertensive function related angiotensin-I-converting enzyme (ACE) inhibitory activities of sweet potato cultivars were determined using rapid in vitro assay models. The purple flesh cv. NIC-413 had significantly higher phenolic content (2.8 mg GAE 100 g−1 FW) and associated high antioxidant activity. Catechin, gallic, and dihydroxybenzoic acids were found in all cultivars, while chlorogenic acid was present only in purple-flesh cultivar. Anti-hyperglycemic property relevant α-amylase (74–84%), and α-glucosidase (21–60%) enzyme inhibitory activities were present in all sweet potato cultivars. Additionally, anti-hypertensive property relevant ACE (10–88%) enzyme inhibitory activity were present across all sweet potato cultivars. The results of this in vitro screening study suggested that sweet potato cultivars like NIC-413, Murasaki, Evangeline, and Covington are good dietary source of phenolic antioxidants and can be relevant for anti-hyperglycemic and anti-hypertensive benefits to target type 2 diabetes associated health risks. [ABSTRACT FROM AUTHOR]

Solanum torvum is one of the plants mentioned in “Kitab Al-Tibb Pontianak”, a historical medical manuscript which encompasses many traditional healings of Malay people for various ailments including of hypertension. This systematic review involves searching within Science Direct, SCOPUS, and PUBMED databases with the aim to find scientific evidences purporting this traditional claim. The keywords such as anti-hypertensive, angiotensin-converting enzyme (ACE) inhibitor, blood pressure, diuretic, vasodilation, Solanum torvum, and S. torvum were used with suitable Boolean operators. Sixteen research articles were finally included in this systematic review after considering some inclusions and exclusions criteria. The evidence that supported S. torvum use for hypertension included its capability in reducing blood pressure in normal and high fructose-induced hypertensive rats, and also its diuretic effect by increasing sodium excretion and total urinary output in normal and in nitric-oxide deprived rats, as well as the ability to inhibit ACE, the key enzyme that mediates consequential increment of blood pressure. On contrary, S. torvum also induced partial vasoconstriction and amplified the hypertensive effect in the nitric-oxide-deprived hypertensive rats. In conclusion, this review found scientific evidence asserting the traditional use of S. torvum for hypertension with some conflicting findings in some study models. Therefore, this ethnomedicinal claim warrants more scientific verification, especially on its effect on the essential hypertension model which is very common in humans but has not yet been explored.

Objective: To investigate the effect of epigallocatechin-3-gallate (EGCG) on endothelial dysfunction in spontaneously hypertensive rats (SHR). Methods: Wistar-Kyoto (WKY) rats and SHR were divided into four groups; WKY control, SHR control and SHR treated with EGCG (50 mg/kg/day) or losartan (10 mg/kg/day). The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days. Acetylcholine-induced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment. The vascular levels of reactive oxygen species, nitric oxide, tetrahydrobiopterin, and cyclic guanosine monophosphate were also measured. Moreover, the expression of angiotensin II type 1 (AT1) receptor protein was determined. Results: The systolic blood pressure was significantly decreased in SHR treated with EGCG. The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group. EGCG also significantly increased the levels of nitric oxide, tetrahydrobiopterin, and cyclic guanosine monophosphate, while decreasing the level of reactive oxygen species and the protein expression of AT1 receptor in SHR. Conclusions: EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability, which may be modulated partly by inhibition of vascular AT1 receptors. An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

Objective: To investigate the effect of epigallocatechin-3-gallate (EGCG) on endothelial dysfunction in spontaneously hypertensive rats (SHR). Methods: Wistar-Kyoto (WKY) rats and SHR were divided into four groups; WKY control, SHR control and SHR treated with EGCG (50 mg/kg/day) or losartan (10 mg/kg/day). The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days. Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment. The vascular levels of reactive oxygen species, nitric oxide, tetrahydrobiopterin, and cyclic guanosine monophosphate were also measured. Moreover, the expression of angiotensin II type 1 (AT1) receptor protein was determined. Results: The systolic blood pressure was significantly decreased in SHR treated with EGCG. The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group. EGCG also significantly increased the levels of nitric oxide, tetrahydrobiopterin, and cyclic guanosine monophosphate, while decreasing the level of reactive oxygen species and the protein expression of AT1 receptor in SHR. Conclusions: EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability, which may be modulated partly by inhibition of vascular AT1 receptors. An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals. [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.

Objective To observe the difference of hypotensive effect of sarcubitril/valsartan between hypertensive patients with increased left atrial diameter (LAD) and with normal LAD. Methods A total of 80 patients who were diagnosed as essential hypertension in Nanjing First Hospital from June 2021 to January 2022 were selected, and they all did not take antihypertensive drugs in the past two weeks. According to the size of LAD, they were divided into first group (LAD≥40 mm, n=50) and second group (LAD＜40 mm, n=30) . After enrollment, all patients were given a daily dose of 100 mg of sarcubitril/valsartan. If the blood pressure reached the standard after 1 week［systolic blood pressure (SBP) ＜140 mmHg and diastolic blood pressure (DBP) ＜90 mmHg］, continue to use 100 mg of sarcubitril/valsartan. If not, increase the dose to 200 mg of sarcubitril/valsartan per day. If the blood pressure reaches the standard after 2 weeks, continue to use 200 mg dose. If the blood pressure does not reach the standard, add it to 400 mg dose per day or add other kinds of antihypertensive drugs according to the patient's individualized situation. The changes of blood pressure level and the rate of reaching the standard of blood pressure in the two groups for 4 weeks (28th day) were observed and compared. Results Compared with second group, the decrease of SBP ［7th day: (11.06±1.36) mmHg vs (7.53±1.31) mmHg, P＜0.01; 14th day: (19.70±2.62) mmHg vs (13.80±1.92) mmHg, P＜0.01］ and the decrease of DBP ［7th day: (5.76±2.63) mmHg vs (4.47±1.31) mmHg, P=0.014; 14th day: (10.02±3.17) mmHg vs (8.23±2.84) mmHg, P=0.013］ were significant higher in the first group. After four weeks, there was no significant difference in SBP, DBP levels and the distribution of proportion of combined use of antihypertensive drugs between the two groups (P＞0.05) . Conclusion Compared with hypertensive patients with normal LAD, sarcubitril/valsartan has a better effect on blood pressure reduction in patients with increased LAD is more superior, and the blood pressure reduction range is very obvious in the first two weeks after use.

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]

Falls are the geriatric syndromes that become one of the main causes of injury, even death in the elderly. It is known that one of the risk factors for falling is the use of certain drugs that have the effect of orthostatic hypotension, sedation, balance disruptions, and other side effects. This study aims to examine the risk of falling based on Morse scale of geriatric patient that use fall-risk drug. Retrospective data were taken from e-prescriptions for geriatric patients and interviews with the patients to determine the risk of falling based on the Morse scale. The results showed that 115 patients who used the fall-risk drug had an average risk of falling from mild to moderate. The high fall-risk drug used by most patients was gabapentin (43%), the moderate fall-risk drug was candesartan (60%), and the low fall-risk drug was furosemide (9%). Patients with the total of 71% received a combination of two to four fall-risk drugs. Total MFRS of ≥6 was 53% patients, meaning that the patients’ using of drugs needed to be evaluated. From the results of statistical analysis, it was found that the number of fall risk drugs received by patients was not associated to the risk of falling in geriatric patients, while increasing the dose of high fall-risk drugs such as gabapentin, increased the fall risk level in geriatric patients. From the result of this study, it is known that fall-risk drugs are widely used by patients, hence it is necessary to increase the awareness of falling in geriatric patients. [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.

Background Long-term chemical drug consumption to treat hypertension may have side effects because the levels are sometimes difficult for the body to tolerate. Therefore, some people have used plants as herbal medicine, including avocado leaves ( Persea americana Mill.) as antihypertensive. This study aims to find out the differences in the effectiveness of modern drugs and natural antihypertensive ingredients in avocado leaf extract (containing flavonoids and quercetin compounds) in inhibiting the ACE enzyme, which causes decreasing systolic blood pressure (SBP) and diastolic blood pressure (DBP) as well as increasing urine volume. Methods This study used an experimental in vivo study design involving 24 white male Wistar rats ( Rattus norvegicus), aged 2–3 months, weighing 130–250 g, and of a healthy condition with active movement. The samples were randomly divided into six treatment groups and post-test only research design with control group design. Results The result of the study showed that avocado leaf extract was effective in reducing blood pressure in Wistar rats with hypertension induced by 16% NaCl for 14 days. SBP fell from 164.92 mmHg to 116.83 mmHg and DBP from 118.42 mmHg to 82.83 mmHg. One-way ANOVA test value significance SBP p=0.000 and Kruskal–Wallis test value of DBP p=0.030, Kruskal–Wallis test urine volume value of p=0.002. The statistical test results proved that avocado leaf extract significantly reduced the blood pressure and increased the urine volume in hypertensive rats. The ACE inhibitor test, performed using an ELISA, showed that the extract inhibition against the ACE enzyme was 60.0±12.1%, serum nitrate levels 41.1±11.5. The decrease in blood pressure occurred because the extract contained a quercetin compound discovered by the high-performance liquid chromatography (HPLC) method of 1129.597 ppm. Conclusions The study showed that the leaf extract of Persea americana Mill. was effective as an antihypertensive.

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]

In the present study, we prepared pea peptides with high angiotensin-converting enzyme (ACE) inhibitory activity in vitro using an enzymatic hydrolysis of pea protein and compounded them with clam peptides to obtain a pea-clam double peptide. The effects of the two-peptide composite and pea peptides on hypertension and the damage-repair of corresponding organs were studied in spontaneously hypertensive rats (SHRs). We found that both pea peptides and the two-peptide composite significantly reduced the blood pressure upon a single or long-term intragastric administration, with the two-peptide composite being more effective. Mechanistically, we found that the two-peptide composite could regulate the renal renin-angiotensin system (RAS), rebalance gut microbial dysbiosis, decrease renal and myocardial fibrosis, and improve renal and cardiac function and vascular remodeling. Additionally, hippocampal lesions caused by hypertension were also eliminated after two-peptide composite administration. Our research provides a scientific basis for the use of this two-peptide composite as a safe antihypertension ingredient in functional foods. [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]

BackgroundCognitive function is a concern among the elderly, which is related to the quality of life, life expectancy, and economic burdens. The relationship between blood pressure (BP) control status, visit-to-visit BP variability, and cognitive function remains controversial.MethodsWe aimed to explore the association between BP control status at baseline, visit-to-visit BP variability, and cognitive function. This study included 3,511 elderlies in the China Health and Retirement Longitudinal Study, covering four waves for 7-year follow-up (baseline 2011, 2013, 2015, and 2018). BP was measured in Wave 2011, 2013, and 2015. Cognitive function was measured by Mini-Mental State Exam in Wave 2018. Participants were divided into two groups: mid-old group for reflecting midlife BP and cognition (45–59 years at baseline but aged 60 or over in Wave 2018), and old-old group for reflecting late-life BP and cognition (aged 60 or over at baseline). We use univariate analysis and general linear model to analyze.ResultsLate-life BP showed stronger associations with cognitive function than midlife BP. As to late-life BP control status, controlled hypertension group get higher cognitive score than uncontrolled hypertension group in language (adjusted β = −0.34, 95%CI −0.68 to 0.00), and untreated hypertension group in orientation (adjusted β = −0.41, 95%CI −0.72 to −0.11), language (adjusted β = −0.35, 95%CI −0.67 to −0.04), and total (adjusted β = −0.99, 95%CI −1.85 to −0.12). Regarding visit-to-visit BP variability, midlife visit-to-visit systolic blood pressure (SBP) variability was associated with language (adjusted β = −3.70, 95% CI −5.83 to −1.57), while late-life visit-to-visit SBP variability was associated with orientation (adjusted β = −2.99, 95% CI −4.84 to −1.14), recall (adjusted β = −1.69, 95% CI −2.89 to −0.48), language (adjusted β = −2.26, 95% CI −4.13 to −0.38), and total (adjusted β = −9.50, 95% CI −14.71 to −4.28); Midlife diastolic blood pressure (DBP) variability and pulse pressure (PP) variability showed a significant relationship with language (adjusted β = 3.25, 95% CI −1.31 to −5.19) and calculation (adjusted β = −0.26, 95% CI −0.47 to −0.04), respectively. No significant correlation was found between midlife BP control status, late-life visit-to-visit DBP variability, late-life visit-to-visit PP variability, and cognitive score. There was no significant correlation between BP and memory.ConclusionsBP control status and visit-to-visit BP variability were significantly related to cognitive function among the Chinese elderly. Receiving effective late-life antihypertensive treatment and keeping SBP stable might contribute to prevent the development of cognitive impairment and dementia, especially for orientation and language function.

There is an increasing amount of evidence that oxidative stress related to hypertension can damage the function of diverse structures such as the aorta and kidney. It is a well-established fact that chlorogenic acid and anthocyanin found in purple sweet potato generates bioactive compound with antihypertensive and anti-ACE activities in RAA system. The present study sought to investigate anti-ACE activities in RAA system of extract ethanol of purple sweet potato (EP) in deoxycorticosterone acetate (DOCA–salt)–induced hypertensive rats (Rattus norvegicus). The rats were orally administrated a 95% ethanol extract of purple sweet potato (var. ayamurasaki) (EP) in a daily dose of 200 and 400 mg/kg body weight also chlorogenic acid (CA) of 700 mg/kg bw for 4 weeks. Activity of renin, ACE, and Ang II concentration were assessed. Inhibiting activity of renin, ACE, and decreasing Ang II concentration after treatment was observed in the DOCA-salt hypertensive rats compared to normotensive group rats; (P

As prodrugs series of new sartan-derived molecules were designed, synthesized, and evaluated. Most of the synthesized compounds could decrease blood pressure efficiently in spontaneously hypertensive rats. It could be ratiocinated that the original drugs could be released from the prodrugs exactly at the connecting position catalyzed by the hydrolyzation enzymes. The maximal response of mean blood pressure (MBP) lowered 70.2 ± 5.0 mmHg (compound I1) and 61.2 ± 1.0 mmHg (compound II1) at 10 mg/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than Losartan and were similar with Telmisartan. Pharmacokinetics test results of I1 were consistent with its antihypertension effects in vivo. The safety was confirmed by the influence on the rats' heart rates and other symptoms which could not be observed during the whole process. Therefore, compounds I1 and II1 could be considered potential antihypertension drug candidates. [ABSTRACT FROM AUTHOR]

The antihypertensive effects of Eucommia ulmoides were determined between normal rats and spontaneously hypertensive rats daily gavaged with leaf extracts, bark extract, chlorogenic acid (CGA), and captopril. Significant composition difference between leaf and bark extracts were noted since CGA was only detected in leaf extract. The overall antihypertensive effects ranked as captopril > CGA > leaf extracts > bark extract, indicating the antihypertensive effect of E. ulmoides extract was CGA-dependent. The hypertension related targets of CGA were screened out and ten KEGG pathways of these targets were significantly enriched, indicating CGA took function in antihypertension via multiple biological processes. Molecular docking revealed CGA bound more tightly to hypertension related targets than captopril, indicating CGA positively participated in antihypertension. However, drug-likeness evaluation displayed the bioavailability of CGA was 5 times lower than captopril, which was consistent with dosage difference in animal experimental. Hence, the antihypertensive effect of CGA was bioavailability limited.

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.

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.

Processing can change the properties and flavors of food. Many plants in the Araceae family can be used as food or medicine, but their raw materials are usually toxic, such as Pinellia ternata tuber (PTT). After processing (processed PTT, PPTT), its toxicity is reduced. However, the mechanism remains unclear. In this study, a novel approach integrating liquid chromatography-mass spectrometry, feature-based molecular networking (FBMN), de novo sequencing, and protein database searching was applied to rapidly discover and characterize peptides in PPTT. Potential antihypertensive peptides were screened using in silico methods, angiotensin I-converting enzyme (ACE) inhibitory assay, and molecular docking analysis. A significant decrease was observed in toxic lectins after processing. Meanwhile, a total of 1954 mass spectral nodes were discovered in PPTT, of which 130 were annotated as peptides by FBMN. These peptides, ranging from 2 to 21 amino acids, were rapidly identified using PEAKS. Notably, 98 peptides were derived from lectins, most of which increased after processing. Approximately 30% of identified peptides were screened for potential high antihypertensive activity in silico . Five peptides exhibited inhibitory effects on ACE, with two showing IC 50 values of 131 and 185 μM. Dynamic profiling indicated that 7-9 days of processing is optimal for reducing toxicity and enhancing efficacy. More importantly, these peptides were also found in commercial PPTT, confirming their bioactivity contributions. These findings provide insights into the mechanism by which food processing drives the toxic lectin reduction and bioactive peptide enhancement in PTT, providing a novel approach to rapidly discover bioactive peptides, which can be extended to other foods in Araceae family., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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]

Peperomia pellucida (L.) Kunth has been used widely to treat headache, kidney disease, fever, and hypertension. Previous in vitro studies discovered that the flavonoid-rich extract of this plant has potential hypotensive effects, specifically angiotensin-converting enzyme (ACE)-inhibitory activity. However, there is insufficient scientific evidence to validate the result in vivo. This study investigated the dose dependencies of the effects of the ethyl acetate fraction of the ethanolic extract of this plant on blood pressure and biomarkers associated with the renin–angiotensin–aldosterone systems (RAAS), such as angiotensin II (AII) and the plasma renin concentration (PRC). In total, 30 two-kidney, one-clip (2K1C) hypertensive model rats were divided into five groups (n = 6 each): model group, captopril 25 mg/kg BW group, and three different ethyl acetate groups (25, 50, and 100 mg/kg BW). Another six rats comprised the sham group. Renal hypertensive rats (RHRs) were generated using stainless steel modification clips. Drugs were administered via oral gavage for 2 consecutive weeks. Blood pressure was measured weekly prior to treatment. Blood samples were collected before treatment and after the last dose to measure AII and PRC. The left kidney was isolated for histopathological examination. Blood pressure, AII levels, and PRC were elevated after 6 weeks in RHRs. Treatment with captopril and the ethyl acetate fraction of P. pellucida (L.) Kunth decreased blood pressure, AII levels, and PRC. The ethyl acetate fraction at a dose of 50 mg/kg BW had similar ACE-inhibitory effects as captopril. Histopathological examination disclosed coagulative necrosis in clipped kidneys. Impairment was alleviated in a dose-dependent manner by P. pellucida (L.) Kunth, similarly as observed in the captopril group. P. pellucida (L.) Kunth targets the renin–angiotensin–aldosterone system, which might explain its antihypertensive effects. [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]

In our previous study, the clams (Ruditapes philippinarum) were inoculated with Bacillus natto and fermented to produce peptides (RBPs) with high ACE inhibitory effect in vitro. In this study, we continued to explore the anti-hypertensive effect and potential mechanisms of RBPs in vivo. The results showed that RBPs significantly reduced both systolic and diastolic blood pressure and alleviated the damage of kidney, thoracic aorta and heart of spontaneously hypertensive rats after 8 weeks of treatment. Meanwhile, RBPs could also inhibit the expression of RAS signaling pathway, maintained the secretion balance of NO/ET-1 in vascular endothelial cells and inhibited the cardiac TGF-β/Smad pathway. Most notably, RBPs could also improve the gut microbiota by decreasing the ratio of Firmicutes and Bacteroidetes and increasing the relative abundance of certain genera, like Ruminococcaceae_UCG-014. The data suggested that RBPs could be used as functional food ingredient for the improvement of hypertension.

Cardiovascular disease stands as the leading cause of death globally, with hypertension emerging as an independent risk factor for its development. The worldwide prevalence of hypertension hovers around 30%, encompassing a staggering 1.2 billion patients, and continues to escalate annually. Medication plays a pivotal role in managing hypertension, not only effectively regulating blood pressure (BP) but also substantially mitigating the occurrence of cardiovascular and cerebrovascular diseases. This review comprehensively outlines the categories, mechanisms, clinical applications, and drawbacks of conventional antihypertensive drugs. It delves into the five primary pharmacological classifications, namely β-receptor blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and diuretics. The emphasis is placed on elucidating the mechanisms, advantages, and research progress of novel antihypertensive drugs targeting emerging areas. These include mineralocorticoid receptor antagonists (MRAs), atrial natriuretic peptides (ANPs), neutral endopeptidase inhibitors (NEPIs), sodium-dependent glucose transporter 2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), endothelin receptor antagonists (ERAs), soluble guanylate cyclase (sGC) agonists, brain aminopeptidase A inhibitors (APAIs), and small interfering ribonucleic acids (siRNAs) targeting hepatic angiotensinogen. Compared to conventional antihypertensive drugs, these novel alternatives exhibit favorable antihypertensive effects with minimal adverse reactions. This review serves as a valuable reference for future research and the clinical application of antihypertensive drugs.

The purpose of this study was to investigate the antihypertensive effect of camellia oil in vivo and its potential ACE-pathway mechanism. The results showed that the contents of oleic acid and linoleic acid in camellia oil were 78.83% and 8.32%, respectively. In vivo experimental results exhibited that both low-dose and high-dose groups significantly reduced the systolic blood pressure (SBP) in acute and long-term administration experiments compared to the control group. Camellia oil with various dosages significantly reduced the angiotensin-converting enzyme (ACE) activities of tissues and the levels of endothelin, renin and angiotensin II in serum. Moreover, camellia oil performed a similar reduction level on SBP of spontaneously hypertension rats (SHRs) for both captopril and olive oil. Overall, camellia oil exert antihypertension effect by modulating the balance of endothelium-derived vasoconstrictor and relaxing factors in serum.

Objectives:There is an increasing number of complex diseases that are progressively more difficult to be controlled using the conventional “single compound, single target” approach as demonstrated in our current modern drug development. TCM might be the new cornerstone of treatment alternative when the current treatment option is no longer as effective or that we have exhausted it as an option. Orthogonal stimulus-response compatibility group study is one of the most frequently employed formulas to produce optimal herbal combination for treatment of multi-syndromic diseases. This approach could solve the relatively low efficacy single drug therapy usage and chronic adverse effects caused by long terms administration of drugs that has been reported in the field of pharmacology and medicineMethods:The present review was based on the Science Direct database search for those related to the TCM and the development of antihypertensive TCM herbal combination using orthogonal stimulus-response compatibility group studies approach.Results:Recent studies have demonstrated that the orthogonal stimulus-response compatibility group study approach was most frequently used to formulate TCM herbal combination based on the TCM principles upon the selection of herbs, and the resulting formulated TCM formula exhibited desired outcomes in treating one of global concerned complex multi-syndromic diseases, the hypertension. These promising therapeutic effects were claimed to have been attributed by the holistic signaling mechanism pathways employed by the crude combination of herbs.Conclusion:The present review could serve as a guide and prove the feasibility of TCM principles to be used for future pharmacological drug research development.

Hypertension is widely known as cardiovascular disease. In addition to resulting heart failure, hypertension can result in kidney failure and cerebrovascular disease. This study was aimed to determine the percentage of treatment rationality of hypertensive patient treatment outpatient in Puskesmas Siantan Hilir Pontianak 2015 which includes the appropriate indication, appropriate drug, appropriate patient, and appropriate dose based on the guideline JNC 7. This study was cross-sectional observational study using retrospective data such as medical records of outpatient hypertension patients in 2015. The total of sample for this research were 92 people. The percentage of using the angiotensin converting enzym inhibitor (captopril) was 47,46%; calcium channel blocker (amlodipine) was 34,75%; tiazid diuretic (hydrochlorothiazid) was 16,10%; loop diuretic (furosemid) was 0, 85%; and potassium sparing (spironolactone) was 0.85%. The therapy rasionality of hypertensive patients in this research were 100% appropriate indication, 70,65% appropriate drug, 100% appropriate patient and 98,91% appropriate dose. The conclusion of this study is that overall treatment that meets all four rational treatment criteria is 69.56%.