Angiotensin-converting Enzyme Activity Research Articles

Effects of n-hexane fraction of Piper guineense seed extracton Nω-nitro-L-arginine methyl ester hydrochloride-induced hypertension in rats.

This study aimed to investigate the effects of the n-hexane fraction of the ethanolic seed extract of PG (NFESEPG)on hypertension induced by Nω-nitro-L-argininemethyl ester (L-NAME)in rats. Specifically, the study examined the impact of NFESEPG on blood pressure, oxidative stress markers, NO concentration, angiotensin-converting enzyme (ACE) and arginase activities, and cardiac biomarkers in hypertensive rats. The study involved collecting, identifying, and processing the PG plant to obtain the ethanolic seed extract. The extract was then partitioned with solvents to isolate the n-hexane fraction. Hypertension was induced in rats by oral administration of L-NAMEfor 10 days, while concurrent treatment with NFESEPG at two doses (200 and 400 mg/kg/day) was administered orally. Blood pressure was measured using a noninvasive tail-cuff method, and various biochemical parameters were assessed. Treatment with both doses of NFESEPG significantly reduced systolic and diastolic blood pressure in L-NAME-inducedhypertensive rats. Additionally, NFESEPG administration increased NO concentration and decreased ACE and arginase activities, malondialdehyde (MDA) levels, and cardiac biomarkers in hypertensive rats. The findings indicate that NFESEPG effectively lowered blood pressure in hypertensive rats induced by L-NAME,potentially through mechanisms involving the modulation of oxidative stress, NO bioavailability, and cardiac biomarkers. These results suggest the therapeutic potential of NFESEPG in managing hypertension and related cardiovascular complications.

Antihypertensive effects of whey protein hydrolysate involve reshaping the gut microbiome in spontaneously hypertension rats

Novel angiotensin-converting enzyme (ACE) inhibitory peptides were identified from whey protein hydrolysates (WPH) in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study. Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension. WPH inhibited ACE activity (20.81 %, P < 0.01), and reduced renin concentration (P < 0.05), thereby reducing systolic blood pressure (SBP) (12.63 %, P < 0.05) in spontaneously hypertensive rats. The increased Akkermansia, Bacteroides, and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention. These changes jointly contributed to low blood pressure. The heart weight and cardiomyocyte injuries (hypertrophy and degeneration) were alleviated by WPH. The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated (Wnt) signaling pathway and Apelin signaling pathway were altered after WPH supplementation. Notably, WPH alleviated serum oxidative stress, indicated by the decreased malondialdehyde content (P < 0.01), enhanced total antioxidant capacity (P < 0.01) and superoxide dismutase activity (P < 0.01). The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements.

Proteomic Analysis of Human Macrophages Overexpressing Angiotensin-Converting Enzyme.

Angiotensin converting enzyme (ACE) exerts strong modulation of myeloid cell function independently of its cardiovascular arm. The success of the ACE-overexpressing murine macrophage model, ACE 10/10, in treating microbial infections and cancer opens a new avenue into whether ACE overexpression in human macrophages shares these benefits. Additionally, as ACE inhibitors are a widely used antihypertensive medication, their impact on ACE expressing immune cells is of interest and currently understudied. In the present study, we utilized mass spectrometry to characterize and assess global proteomic changes in an ACE-overexpressing human THP-1 cell line. Additionally, proteomic changes and cellular uptake following treatment with an ACE C-domain selective inhibitor, lisinopril-tryptophan, were also assessed. ACE activity was significantly reduced following inhibitor treatment, despite limited uptake within the cell, and both RNA processing and immune pathways were significantly dysregulated with treatment. Also present were upregulated energy and TCA cycle proteins and dysregulated cytokine and interleukin signaling proteins with ACE overexpression. A novel, functionally enriched immune pathway that appeared both with ACE overexpression and inhibitor treatment was neutrophil degranulation. ACE overexpression within human macrophages showed similarities with ACE 10/10 murine macrophages, paving the way for mechanistic studies aimed at understanding the altered immune function.

Persistent Vascular Complications in Long COVID: The Role of ACE2 Deactivation, Microclots, and Uniform Fibrosis.

Angiotensin-converting enzyme 2 (ACE2), a key regulator in vasoregulation and the renin-angiotensin system, is hypothesized to be downregulated in patients with COVID-19, leading to a cascade of cardiovascular complications. This deactivation potentially results in increased blood pressure and vessel injury, contributing to the formation and persistence of microclots in the circulation. Herein, we propose a hypothesis regarding the prolonged vascular complications observed in long COVID, focusing on the role of ACE2 deactivation and/or shedding, the persistence of microclots, and the unique pattern of fibrosis induced by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Furthermore, we propose that the distinctive, uniform fibrosis associated with COVID-19, which is challenging to detect through conventional X-ray imaging, exacerbates vascular injury and impairs oxygenation. The persistence of these microclots and the unique fibrosis pattern are suggested as key factors in the extended duration of vascular complications post-COVID-19 infection, regardless of the initial disease severity. Moreover, plasma ACE2 activity has the potential to serve as prognostic or diagnostic biomarkers for monitoring disease severity and managing long COVID symptoms. Elucidating the role of ACE2 deactivation and the consequent events is vital for understanding the long-term effects of COVID-19. The experimental verification of this hypothesis through in vitro studies, clinical longitudinal studies, and advanced imaging techniques could yield significant insights into the pathophysiological mechanisms underlying long COVID, thereby improving the management of patients, particularly those with cardiovascular complications.

IN VITRO AND IN SILICO INHIBITORY ACTIVITY OF ANGIOTENSIN-CONVERTING ENZYME II AND ANTI-INFLAMMATORY EFFECTS OF NATURAL COMPOUNDS FROM RHEUM OFFICINALE ROOTS

Rhubarb roots (Rheum officinale), a common medicinal plant in folk remedies, and their chemical compositions were investigated for their inhibitory activity of angiotensin-converting enzyme II and anti-inflammatory effects by inhibiting NO production and IL-6 expression. Four natural compounds, including two anthraquinones, chrysophanol (2) and emodin (3), and two stilbenes, rhapontigenin (1) and trans-piceatannol (4), were isolated from the roots of Rhubarb. The results showed that rhapontigenin (1) exhibited an inhibitory effect on the ACE-2 enzyme with an IC50 value of 132 mM. In an in silico study, rhapotigenin (1) had a binding energy value of -9.32 kcal/mol, lower than MLN-4760, on ACE-2. Both rhapontigenin (1) and emodin (3) exhibited inhibitory activity on NO production in primary cultures of macrophages RAW264.7, with IC50 values ranging from 5.65 to 32.3 µg/mL. This is the first study of the anti-ACE-2 and anti-inflammatory activity of Rhubarb root extract and its constituents.

HPLC phytochemical profiling, antioxidant activity and in vitro evaluation of inhibitory effects of Terminalia catappa stem bark extract on enzymes linked to diabetes, hypertensive vasoconstriction and erectile dysfunction

BackgroundTerminalia catappa is a traditional medicinal plant used for several ailments among the local folks. Among the locals, the stem bark is an important constituent of polyherbal remedies for the treatment of cancer and metabolic diseases; however, there is a paucity of scientific reports on it. This study aimed to evaluate the in vitro antidiabetic, antihypertensive and antierectile dysfunction effects of Terminalia catappa stem bark extract (TSBE). MethodsThe HPLC phytochemical profiling, total phenol content, total flavonoid content and antioxidant capacity of the extract were delineated. The inhibitory effects of TSBE on activities of α-glucosidase, α-amylase, acetylcholinesterase (AChE), arginase, phosphodiesterase-5′ (PDE-5′), angiotensin-converting enzyme (ACE) and ecto-5 nucleotidase (Ecto-5-NTD) were estimated following standard procedures. ResultsHPLC of TSBE profiled ferulic acid, gallic acid, caffeic acid, catechin, rutin, p-coumaric acid, chlorogenic acid, kaempferol, apiginin and quercetin. TSBE had IC50 values of 49.19 µg/mL and 55.42 µg/mL in terms of scavenging DPPH and NO radicals, respectively. The TSBE inhibited α-glucosidase and α-amylase activities with IC50 values of 71.53 µg/mL and 105.11 µg/mL, respectively. The inhibitory effects of TSBE on AChE, arginase, PDE-5′, and ACE revealed IC50 values higher than that of standards. TSBE demonstrated a stimulatory effect on ecto-5-NTD activity. ConclusionTSBE revealed promising antioxidant, antidiabetic, antihypertensive and antierectile dysfunction (anti-ED) properties which may be associated with the bioactive compounds present in the extract.

Recent Advances in the Therapeutic Potential of Carotenoids in Preventing and Managing Metabolic Disorders.

Carotenoids constitute compounds of significant biological interest due to their multiple biological activities, such as antimicrobial, anticancer, antiadipogenic, antidiabetic, and antioxidant properties. Metabolic syndrome (MetS) comprehends a series of metabolic abnormalities (e.g., hypertension, obesity, and atherogenic dyslipidemia) that can affect children, adolescents, and the elderly. The treatment of MetS involves numerous medications, which, despite their efficacy, pose challenges due to prolonged use, high costs, and various side effects. Carotenoids and their derivatives have been proposed as alternative treatments to MetS because they reduce serum triglyceride concentrations, promote insulin response, inhibit adipogenesis, and downregulate angiotensin-converting enzyme activity. However, carotenoids are notably sensitive to pH, light exposure, and temperature. This review addresses the activity of carotenoids such as lycopene, lutein, fucoxanthin, astaxanthin, crocin, and β-carotene towards MetS. It includes a discussion of sources, extraction methods, and characterization techniques for analyzing carotenoids. Encapsulation approaches are critically reviewed as alternatives to prevent degradation and improve the biological performance of carotenoids. A brief overview of the physiopathology and epidemiology of the diseases, including MetS, is also provided.

SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2.

In this study, we investigated whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein may modify angiotensin-converting enzyme 2 (ACE2) activity in the plasma, heart, kidney, liver, lung, and six brain regions (amygdala, brain stem, cortex, hippocampus, hypothalamus, and striatum) of diabetic and hypertensive rats. We determine ACE2 activity in the plasma and lysates of heart, kidney, liver, lung, and six brain regions. MLN-4760 inhibits ACE2 activity in the plasma and all organs. On the other hand, soluble ACE2 (sACE2) activity increased in the plasma of diabetic rats, and there was no change in the plasma of hypertensive rats. ACE2 activity was augmented in the liver, brain stem, and striatum, while it decreased in the kidney, amygdala, cortex, and hippocampus of diabetic rats. ACE2 activity increased in the kidney, liver, and lung, while it decreased in the heart, amygdala, cortex, and hypothalamus of hypertensive rats. We measured the ACE2 content via enzyme-linked immunosorbent assay and found that ACE2 protein levels increased in the heart, while it decreased in the plasma, kidney, brain stem, cortex, hippocampus, hypothalamus, and striatum of diabetic rats. ACE2 protein levels decreased in the brain stem, cortex, hippocampus, and hypothalamus of hypertensive rats. Our data showed that the spike protein enhanced ACE2 activity in the liver and lungs of diabetic rats, as well as in the heart and three of the brain regions (cortex, hypothalamus, and striatum) of hypertensive rats.

Consumption of a Byproduct of Chia Seed Oil Extraction by Cold Pressing Ameliorates Cardiovascular Risks Factors in an Experimental Model of Metabolically Unhealthy Normal Weight.

The byproduct of Salvia hispanica (chia) seed oil extraction by cold pressing, also known as expeller, possesses a high nutritional value. It is rich in proteins, fibers, minerals, and has a residual oil content of 7-11%, which is rich in omega 3 linolenic acid (ALA). However, this byproduct has been historically undervalued. Thus, the aim of current work was to study the effects of consuming of a rich in chia expeller diet on a rabbit model of metabolically unhealthy normal weight to validate their use as a functional food. Rabbits were fed different diets for a period of 6 weeks: a standard diet (CD), a high-fat diet (HFD), a rich in expeller CD (Exp-CD) and a rich in expeller HFD (Exp-HFD). The Exp-HFD attenuated the rise in basal glucose, TyG index, triglycerides, cholesterol and non-HDL cholesterol induced by the HFD. Both rich in expeller diets reduced mean arterial blood pressure (MAP) and increase liver and fat ALA levels compared to their respective controls. Furthermore, the angiotensin converting enzyme (ACE) activity was lower in the lungs of animals fed on rich in expeller diets compared to their respective controls. In vitro studies showed that ALA inhibited ACE activity. The evaluation of vascular reactivity revealed that rich in expeller diets improved angiotensin II affinity and reduced contractile response to noradrenaline. In conclusion, the consumption of rich in expeller diets showed beneficial effects in preventing cardiovascular risk factors such as insulin resistance, dyslipidemia and MAP. Therefore, its use as functional ingredient holds significant promise.

Development of Pomegranate Aloe Vera Juice: Pomalo

Abstract: Pomegranate juice is a good source of polyphenols and has good antioxidant potential, whereas, the studies on pomegranate juice have shown that it possesses antiatherogenic, antioxidant, antihypertensive, and anti-inflammatory properties. The literature also reported the major decrease in atherosclerotic lesion region in immune-deficient mice and intima media thickness in cardiac patients on medications, due to consumption of pomegranate juice. Whereas, in patients with type 2 diabetes, a reduction in lipid peroxidation was observed and in hypertensive patients, a systolic blood pressure and serum angiotensin converting enzyme activity was determined. Therefore, the study showed the potential cardioprotective advantages of pomegranate juice and suggests the inclusion of this juice in a diet for a healthy living. the composition of aloe vera and its role in development of functional foods. The colorless and watery gel-like consistency are the characteristics of aloe vera gel that makes it better option for blend beverages. The functional characteristics render aloe vera with broad range of application in the pharmaceutical, cosmetics and food sectors. The presence of antioxidants and hormones (auxins and gibberellins) in aloe vera, are responsible for preventing chronic diseases and wound healing properties by inducing the cell propagation, thus providing anti-inflammatory action, respectively. Saponins and salicylic acid present in it, provides antibacterial and antiseptic activity. The literature also reveals that emidine and aloin are the compounds present in aloe that act as antiviral, antibacterial and analgesic agent. Whereas, it also contains vitamins E, C and minerals such as, copper, selenium and zinc, along with enzyme brady kinase, fatty acids and sugar, essential and non-essential amino acids, 12 anthraquinones phenolic compounds. The most abundant monosaccharide and polysaccharides found in aloe vera are Mannose-6-phosphate, and glucomannans, respectively.

Food-Derived Up-Regulators and Activators of Angiotensin Converting Enzyme 2: A Review.

Angiotensin-converting enzyme 2 (ACE2) is a key enzyme in the renin-angiotensin system (RAS), also serving as an amino acid transporter and a receptor for certain coronaviruses. Its primary role is to protect the cardiovascular system via the ACE2/Ang (1-7)/MasR cascade. Given the critical roles of ACE2 in regulating numerous physiological functions, molecules that can upregulate or activate ACE2 show vast therapeutic value. There are only a few ACE2 activators that have been reported, a wide range of molecules, including food-derived compounds, have been reported as ACE2 up-regulators. Effective doses of bioactive peptides range from 10 to 50 mg/kg body weight (BW)/day when orally administered for 1 to 7 weeks. Protein hydrolysates require higher doses at 1000 mg/kg BW/day for 20 days. Phytochemicals and vitamins are effective at doses typically ranging from 10 to 200 mg/kg BW/day for 3 days to 6 months, while Traditional Chinese Medicine requires doses of 1.25 to 12.96 g/kg BW/day for 4 to 8 weeks. ACE2 activation is linked to its hinge-bending region, while upregulation involves various signaling pathways, transcription factors, and epigenetic modulators. Future studies are expected to explore novel roles of ACE2 activators or up-regulators in disease treatments and translate the discovery to bedside applications.

Toxicity study and effect of protein hydrolysates derived from black tilapia (Oreochromis placidus) on hypertensive induced mice

Protein hydrolysates are specific protein fragments, produced during enzymatic hydrolysis and can exert various biological functions. The present study investigated the acute toxicity study of protein hydrolysates derived from black tilapia (Oreochromis placidus) and their effect on hypertensive-induced mice. Protein hydrolysates were produced from black tilapia protein isolate through enzymatic hydrolysis. A single dose of protein hydrolysates at 2000 mg/kg of body weight was administered and any changes were observed for 14 days. During 14 days, there were no significant changes in liver enzyme content and kidney function content, adverse clinical signs and mortality. The effect of the administration of protein hydrolysates in hypertensive-induced mice was studied. The body weight, blood pressure, full blood count {red blood cell (RBC), white blood cell (WBC) and platelets} were observed. Hypertensive mice (systolic blood pressure; 161±3 mm/Hg) were fed with pellet consisting of protein hydrolysates at different concentrations as well as carvedilol and combination of carvedilol and protein hydrolysates and systolic blood pressure was monitored. After 28 days, there was a significant reduction of blood pressure in the group of carvedilol (107±4 mm/Hg), 5% protein hydrolysate (119±1 mm/Hg), 10% protein hydrolysate (123±1 mm/Hg), 20% protein hydrolysate (115±2 mm/Hg) and 10% protein hydrolysate in combination with carvedilol (103±2 mm/Hg). Red blood cells significantly increased in hypertension mice but no significant changes in white blood cells and platelets after 28 days. Administration of protein hydrolysates reduced red blood cell levels similar to control group. A significant increase in body weight was observed in hypertension mice administered with protein hydrolysates at different concentrations as well as carvedilol and a combination of carvedilol and protein hydrolysates compared to control group and hypertensive group. Studies on any changes in liver enzyme level, kidney function level and angiotensin converting enzyme (ACE) activity on blood serum were carried out. Results showed that treatment with protein hydrolysates on hypertensive-induced mice reduced liver enzyme levels (ALP, ALT and GGT) and kidney function levels (Na+, K+ and Cl-) to normal levels. ACE enzyme activity of hypertensive-induced mice in the serum was also reduced similar to control mice after being treated with protein hydrolysates.

#1182 Arterial hypertension and chronic obstructive pulmonary disease—problems of choice of therapy

Abstract Background and Aims The development of hypertension in COPD is based on the early formation of endothelial dysfunction in the small and large circulatory circles, increased sympathetic activity with an imbalance in the synthesis of catecholamines, a violation of the role of the lungs in the metabolism of vasoactive substances, oxidative stress, chronic systemic inflammation, an imbalance in the renin-angiotensin-aldosterone system (RAAS). There are few studies confirming the role of RAAS components in the pathogenesis of cardiovascular changes in patients COPD. The activity of angiotensin converting enzyme (ACE) increases with hypoxia, which may play an important role in increasing the degree of systemic hypertension. An increase in the function of the RAAS is possible both under the direct influence of hypoxia and indirectly through activation of the sympathoadrenal system. To evaluate the efficacy and tolerability of the angiotensin II receptor antagonist valsartan (Nortivan) at a dose 80-160 mg per day in patients with hypertension of 1-2 degrees and COPD of stage II-IV. Method The study design is a local, open, incomparable study on the efficacy and safety of the drug Nortivan in patients with hypertension in combination with COPD. We examined 18 patients with stage II-IV in remission, suffering from grade I and II hypertension, determined in accordance with the generally accepted classification of blood pressure levels (VNOK, 2010). Results The criteria for exclusion from the study were the presence in patients of complications of hypertension, coronary heart disease, decompensated chronic pulmonary heart, endocrine diseases requiring drug correction, kidney pathology, chronic heart failure, oral steroid therapy. 10 days in the last 6 months before inclusion in the study, oncological diseases and any other conditions that could interfere with the interpretation and evaluation of the results of the study. Patients who had not previously received antihypertensive treatment were included in the study immediately, and the rest underwent a washing period for 2 weeks. Patients received Nortivan as antihypertensive therapy for 24 weeks. The effectiveness of therapy was controlled by daily monitoring blood pressure. The choice of quality criteria for the effectiveness of therapy parameters SMAD is associated with literature data and own observations on the prevalence of diurnal blood pressure profiles in patients with hypertension and COPD with no decrease or increase in blood pressure at night, when office blood pressure figures are to a lesser extent reflect the effectiveness of antihypertensive therapy. The initial dosage was 80 mg/day. With insufficient hypotensive effect, the dose of the drug was doubled at the 4th week of treatment. The basic COPD therapy did not change throughout the study period and included anticholinergic drugs (ipratropium bromide, tiotropium bromide), beta2-adrenomimetic (fe-noterol) or a combination thereof. Initially and after 24 weeks of treatment, a complete laboratory examination was performed: a clinical blood test, a biochemical blood test. The thickness of the intima-media complex of the carotid arteries and ECG was also studied. The criterion The safety of the therapy was assessed by the indicators of respiratory function, daily pulse oximetry. Conclusion The use of the drug Nortivan has shown high efficacy and safety in patients Grade I–II hypertension in combination with stage II-IV COPD. A statistically and clinically significant normalization of SMAD indicators with correction of pathological types of daily curves due to a decrease in the number of patients with an increase in or the absence of a decrease in blood pressure during the night period. The safety of using the drug in the clinical group with bronchial obstruction syndrome was confirmed by the dynamics of ventilation indicators according to spirometry and the results of daily pulse oximetry, which showed the absence of exacerbation of hypoxia during therapy.

New oxadiazol‐5‐ones derivatives and their performance as angiotensin‐converting enzyme (ACE) inhibitors

AbstractAngiotensin‐converting enzyme inhibitors are widely used in treating arterial hypertension, acting on the renin‐angiotensin‐aldosterone system and controlling blood pressure. We present a novel, greener, and faster methodology to assess the 1,2,4‐oxadiazol‐5‐one ring and perform molecular modifications to obtain angiotensin‐converting enzyme (ACE) inhibitors using this heterocyclic core. Molecular docking simulations indicate that the tested compounds exhibited an affinity for the ACE binding site, with scores comparable to the commercial inhibitor lisinopril. However, in vitro assays revealed that the compounds were ineffective in inhibiting ACE activity. The lack of inhibition may be related to the compounds' more apolar nature. These results emphasize the importance of integrating computational and experimental approaches in developing new drugs, providing valuable insights for planning future studies to optimize the activity of synthesized compounds.

Novel Angiotensin-Converting Enzyme-Inhibitory Peptides Obtained from Trichiurus lepturus: Preparation, Identification and Potential Antihypertensive Mechanism.

Peptides possessing antihypertensive attributes via inhibiting the angiotensin-converting enzyme (ACE) were derived through the enzymatic degradation of Trichiurus lepturus (ribbonfish) using alkaline protease. The resulting mixture underwent filtration using centrifugation, ultrafiltration tubes, and Sephadex G-25 gels. Peptides exhibiting ACE-inhibitory properties and DPPH free-radical-scavenging abilities were isolated and subsequently purified via LC/MS-MS, leading to the identification of over 100 peptide components. In silico screening yielded five ACE inhibitory peptides: FAGDDAPR, QGPIGPR, IFPRNPP, AGFAGDDAPR, and GPTGPAGPR. Among these, IFPRNPP and AGFAGDDAPR were found to be allergenic, while FAGDDAPRR, QGPIGPR, and GPTGPAGP showed good ACE-inhibitory effects. IC50 values for the latter peptides were obtained from HUVEC cells: FAGDDAPRR (IC50 = 262.98 μM), QGPIGPR (IC50 = 81.09 μM), and GPTGPAGP (IC50 = 168.11 μM). Peptide constituents derived from ribbonfish proteins effectively modulated ACE activity, thus underscoring their therapeutic potential. Molecular docking and modeling corroborated these findings, emphasizing the utility of functional foods as a promising avenue for the treatment and prevention of hypertension, with potential ancillary health benefits and applications as substitutes for synthetic drugs.

Systematic Review: JAK-STAT Regulation and Its Impact on Inflammation Response in ARDS from COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a global impact and resulted in millions of deaths worldwide. The course of the Janus kinase signaling transducers and activators (JAK-STAT) pathway is an important molecular pathway that is involved in the cellular response to various cytokines and growth factors promoting an inflammatory response. The overactivation of the JAK-STAT signaling pathway in coronavirus disease 2019 (COVID-19) and its effect on acute respiratory distress syndrome (ARDS)-induced inflammatory processes was observed in various clinical articles that focused on JAK-STAT regulation regarding angiotensin converting enzyme 2 (ACE2) expression and cytokine storm release. Down-regulation of the JAK-STAT signaling pathway through inhibitors decreases the inflammatory response by decreasing cytokine storm release. However, the increased regulation of JAK-STAT in severe COVID-19 patients caused cytokines such as interferon alpha (IFN-α) to promote the phosphorylation of STATs. This response indicated an imbalance with JAK-STAT regulation and its inability to induce the transcription of interferon stimulated response elements. Furthermore, an increase in ACE2 regulation was noted to also increase JAK-STAT signaling, yet the down-regulation of JAK-STAT signaling can result in the overexpression of ACE2 by binding to SARS-CoV-2 and increasing STAT1 expression. Data suggest that inflammatory cytokines enhance the activation of ACE2 in endothelial cells via JAK-STAT pathway. Increasing the regulation of the JAK-STAT signaling pathway enhances the release of cytokines such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), further expressing ACE2. The expression of ACE2 regulates STAT1 and STAT2 expression, leading to the up-regulation of the inflammasomal complexes in hyper-inflammatory responses from the JAK-STAT pathway. Through the review of various clinical reports, the effect of the JAK-STAT signaling pathway on ARDS-induced inflammatory response was observed and correlated with the expression of ACE2 and cytokine storm release in severe COVID-19 cases.

Long-term intake of corn gluten meal protein hydrolysate attenuated hypertension development and modulated associated plasma metabolite levels in spontaneously hypertensive rats

This study evaluated the long-term antihypertensive effect of corn gluten meal protein hydrolysate (CGM-H) on spontaneously hypertensive rats (SHRs). Plausible pathways governing blood pressure were also evaluated based on untargeted metabolomic analysis. The casein diet containing 1 % of CGM-H and peptides obtained from ultrafiltration membranes attenuated the development of hypertension in SHRs after a 6-week oral administration with similar efficacy, while the control group showed progressive hypertension. Plasma renin and angiotensin converting enzyme (ACE) activity and total peroxides level of the corn peptides-treated groups decreased when compared with the control (p < 0.05). In addition, the corn peptides up-regulated antihypertensive metabolites such as prostaglandin K2 and 11-ketotestosterone, while corticosterone, biotin, and plasma fatty acids were down-regulated. This study demonstrates that corn peptides did not only inhibit ACE and renin activities, but also modulated the biosynthesis and metabolisms of fatty acids, sex hormones, and aldosterone, which would have contributed to attenuation of hypertension.

Screening and rational identification of a novel angiotensin-converting enzyme C-domain inhibitory peptide from Fabaceae food peptide library

Angiotensin-converting enzyme (ACE), consisting of N-domain and C-domain, is a key regulator of blood pressure. The use of cACE-specific inhibitors helps minimize side effects in clinical applications. Legumes are a good source of proteins containing ACE inhibitory peptides; however, no studies have reported the identification of cACE-specific inhibitory peptides from Fabaceae. In this study, thermal hydrolysates from seeds, sprouts, pods, seedlings, and flowers of legumes were analyzed. Flowers of legumes exhibited a C-domain-preference ACE inhibition and anti-hypertensive effect in rats. Screening the legume peptide library identified a novel cACE inhibitory peptide, SJ-1. This study reported the first identification of cACE inhibitory peptide from Fabaceae foods. SJ-1, identified from the legume flowers, interacted with active site residues of cACE, leading to the inhibition of ACE activity, downregulation of bradykinin levels, and reduction of blood pressure. These findings also suggested the potential of legume proteins as a source of cACE inhibitory peptides.

Hemp seed protein and its hydrolysate compared with casein protein consumption in adults with hypertension: a double-blind crossover study

BackgroundThe effects of consuming hemp seed protein (HSP) as well as its hydrolysate-derived bioactive peptide (HSP+) on blood pressure (BP) has not, to our knowledge, been investigated in humans. ObjectivesWe aimed to investigate how consumption of HSP and its hydrolysate modulates 24-h systolic (SBP) and diastolic BP (DBP) and plasma biomarkers of BP compared with casein. MethodsIn a double-blind, randomized, crossover design trial, 35 adults who had mild hypertension with SBP between 130 and 160 mmHg and DBP ≤110 mmHg were recruited. Participants were randomly assigned to varying sequences of 3 6-wk treatments, 50 g casein/d, 50 g HSP/d, or 45 g HSP plus 5 g HSP-derived bioactive peptides/d (HSP+), separated by a 2-wk washout period. Treatment effects were assessed with a linear mixed model with repeated measures. ResultsCompared with casein, after HSP+ consumption, 24-h SBP and 24-h DBP decreased from 135.1 and 80.0 mmHg to 128.1 ± 1.6 (P < 0.0001) and 76.0 ± 1.4 mmHg (P < 0.0001), respectively, whereas these values were 133.5 ± 1.6 and 78.9 ± 1.4 mmHg after HSP consumption (P < 0.0001). There were no differences between the HSP and HSP+ consumption in plasma angiotensin-converting enzyme (ACE) activity, renin, or nitric oxide (NO) concentrations. However, these 2 treatments were able to lower both ACE and renin activities and raise NO concentration in plasma compared with casein. ConclusionsThese results suggest that hemp protein consumption, as well as in combination with bioactive peptides, may have a role in the dietary management of hypertension.This trial was registered at clinicaltrials.gov as NCT03508895.

Urinary angiotensin-converting enzyme 2 and its activity in cats with chronic kidney disease.

Angiotensin-converting enzyme 2 (ACE2) played an important role in the renin-angiotensin-aldosterone system (RAAS) and it was proved to be renoprotective in renal disease. Urinary angiotensin-converting enzyme 2 (uACE2) has been shown to reflect renal injury in human and experimental studies, but its role in feline kidney disease remains unknown. Our objectives involve comparing uACE2 concentrations and activities in cats across CKD stages with healthy controls, investigating the relationship between uACE2 concentrations, activities, and clinicopathological data in feline CKD patients, and assessing the predictive abilities of both for CKD progression. A retrospective, case-control study. The concentration and activity of uACE2 were measured by commercial ELISA and fluorometric assay kits, respectively. The concentration was adjusted to give uACE2 concentration-to-creatinine ratios (UACCRs). In total, 67 cats consisting of 24 control and 43 chronic kidney disease (CKD), including 24 early-stage CKD and 19 late-stage CKD, were enrolled in this study. UACCR values were significantly higher in both early-stage (2.100 [1.142-4.242] x 10-6) and late-stage feline CKD (4.343 [2.992-5.0.71] x 10-6) compared to healthy controls (0.894 [0.610-1.076] x 10-6; p < 0.001), and there was also significant difference between-early stage group and late-stage group (p = 0.026). Urinary ACE2 activity (UAA) was significantly lower in CKD cats (1.338 [0.644-2.755] x pmol/min/ml) compared to the healthy cats (7.989 [3.711-15.903] x pmol/min/ml; p < 0.001). UACCR demonstrated an independent, positive correlation with BUN (p < 0.001), and UAA exhibited an independent, negative correlation with plasma creatinine (p < 0.001). Both UACCR and UAA did not yield significant results in predicting CKD progression based on the ROC curve analysis. uACE2 concentration and activity exhibit varying changes as renal function declines, particularly in advanced CKD cats.