Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.

Valorization of fruit by-products is a crucial area of research for the development of innovative bio-based products. This study investigated the physicochemical properties and health-promoting benefits of date syrup waste, both fermented by Pichia cecembensis or Pichia kudriavzevii (FDSW), and unfermented (CDSW). Metabolomics profiles of these samples were identified post in vitro digestion. FDSW exhibited 42 volatile compounds, including 9 new ones, and contained (-)-epicatechin, tyrosol, and gallic acid. Bioaccessible fractions of FDSW demonstrated substantial α-amylase inhibition, with percentages of 40.7 % and 53.9 %, respectively. FDSW displayed superior cytotoxicity against Caco2 and MCF-7 cancer cell lines, with an average of ∼75 % and 56 %, respectively. Untargeted metabolomics analysis revealed an increase in secondary metabolites, totaling 27 metabolites. LC-QTOF analysis of bioaccessible carbohydrate metabolites in FDSW identified two phytochemical groups, alkaloids, and terpenoids. This study underscores the potential of FDSW for producing value-added bio-based products with desirable characteristics and health benefits.

Introduction: Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly uncontrolled observational studies. There is a lack of head-to-head studies. Methods: This cohort study compares the remodeling effects of angiotensin receptor blockers combined with a neprilysin inhibitor (ARNI) and perindopril in heart failure with reduced ejection fraction (HFrEF) patients between January 2017 and December 2020. Inclusion criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed not more than 2 months prior to treatment onset, and (iv) follow-up echocardiography performed not earlier than 6 months and not later than 18 months posttreatment onset. No prior treatment with renin-angiotensin-aldosterone system inhibitors was permitted in the ARNI group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were analyzed. A two-way repeated measure ANOVA (for normally distributed) and generalized estimating equation test for nonnormally distributed interval dependent variables. Mean comparison between and within groups was performed using the Bonferroni test. Results: Following an average treatment period of 9 months, LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, increments of 11.5% and 11.8% resp. (Bonferroni test [P ≤ .05]). LVEDV was reduced by 8.4 mL and 3.2 mL, and LVESV by 17.9 mL and 10.8 mL for ARNI and perindopril resp. Only the reduction of LVESV for ARNI was statistically significant (P = .007). Conclusion: Both ARNI and perindopril yielded a significant improvement in the LVEF within 9 months. The remodeling effect of ARNI seems stronger because of the greater improvements in left ventricular volumes.

Chickpea seeds are the source of proteins in human nutrition and attribute some nutraceutical properties. Herein, we report the effects of chickpea seed bioactive peptide on albumin, insulin, lactoglobulin and lysozyme amyloid fibril formation. Employing thioflavin T (ThT) assays and circular dichroism (CD), amyloid structural binding transition was experimented to analyze the inhibition of amyloid fibril formation. The purified active peptide with a molecular mass of 934.53 Da was evaluated in vitro for its ACE-I inhibitory, antibacterial, antifungal and antidiabetic activities. Further, in vivo animal studies were carried out in wistar rats for blood pressure lowering action. In hypertensive rats, chickpea peptide decreased 131 ± 3.57 mm of Hg for systolic blood pressure and 86 ± 1.5 mm of Hg for diastolic blood pressure after 8 h intraperitoneal administration. Additionally, the peptide suppressed the fibrillation of amyloid and destabilized the preformed mature fibrils. Data emphasize efficacy of chickpea peptide vis-a-vis ACE-Inhibitory, antibacterial, antifungal, antidiabetic and anti-amyloidogenic activities, allowing us to propose this novel peptide as a suitable candidate for nutraceutical-based drugs and seems the first kind of its nature.

A novel soy chhurpi product was developed by fermentation of soymilk using proteolytic Lactobacillus delbrueckii strains isolated from traditional chhurpi production of Sikkim Himalaya. Soymilk fermentation by L. delbrueckii WS4 was associated with the hydrolysis of globulin proteins, with observed antioxidant, and ACE-inhibitory activity which further increased upon simulated in vitro gastrointestinal digestion. Peptidomics analysis of soy chhurpi and its gastrointestinal digest resulted in the identification of bioactive peptides with ACE-inhibitory and antioxidant properties. In silico antihypertensive property prediction followed by molecular docking study demonstrated strong binding affinity of selected peptides with ACE. The glycinin-derived peptide, SVIKPPTDE escaped gastrointestinal digestion and demonstrated strong non-bond interactions with ACE catalytic residues. QSAR models predicted an ACE-inhibitory IC50 of 21.29 µM for SVIKPPTDE. This is the first report on the production of novel functional soy chhurpi cheese using defined starter strains and the identification of bioactive peptides in undigested and gastrointestinal digested soy chhurpi.

Background: In this study, the profile of urinary EGF excretion (uEGF/uCreat) was mapped in children presenting with prolonged proteinuria or with nephrotic syndrome refractory to or dependent of steroids. We investigated whether uEGF/uCreat could be linked to the underlying biopsy result, taking into account its response to immunosuppressive medication and to ACE inhibition, as well as genetic predisposition. Methods: Ninety-eight pediatric patients with initial presentation of nephrotic syndrome or prolonged proteinuria were included in this study, along with 49 healthy controls and 20 pediatric Alport patients. All patients had a normal kidney function and were normotensive during the course of the study, whether or not under ACE inhibition. In repeated urine samples, uEGF was measured and concentration was normalized by urine creatinine. In order to compare diagnosis on kidney biopsy, genetic predisposition and response of uEGF/uCreat to immunosuppression and to ACE inhibition, uEGF/uCreat is studied in a linear mixed effects model. Results: Patients with Minimal Change Disease (MCD) showed a significantly different profile of uEGF/uCreat in comparison to healthy children, as well as compared to patients with Focal Segmental Glomerulosclerosis (FSGS) or another glomerulopathy on kidney biopsy. The response of uEGF/uCreat to ACE inhibition was absent in minimal change disease and contrasted with an impressive beneficial effect of ACE inhibition on uEGF/uCreat in FSGS and other proteinuric glomerulopathies. Absence of a genetic predisposition was also associated with a significantly lower uEGF/uCreat. Conclusions: Despite preserved kidney function, children with a proteinuric or nephrotic glomerular disease on kidney biopsy show a significantly lower uEGF/uCreat, indicative of early tubulo-interstitial damage, which appears reversible under ACE inhibition in any underlying glomerulopathy except in minimal change disease. In view of the distinct profile of uEGF/uCreat in minimal change disease compared to other glomerulopathies, and the link between genetic predisposition and uEGF/uCreat, our study suggests that uEGF/uCreat can be a helpful tool to decide on the need for a renal biopsy in order to differentiate minimal change disease from other proteinuric glomerular diseases.

The purpose of this study was to develop an in-vitro digestion protocol to evaluate the antioxidant potential of the peptides found in processed cheddar cheese using digestion enzymes. We first studied antioxidant and angiotensin-converting enzyme (ACE) inhibition and antioxidant activities of processed cheddar cheese with the addition of spices e.g., cumin, clove, and black pepper made from buffalo milk and ripened for 9 months. Then we conducted an in vitro digestion of processed cheddar cheese by gastric and duodenal enzymes. Freeze-dried water (WSE) and ethanol-soluble fractions (ESE) of processed cheddar cheese were also monitored for their ACE inhibition activity and antioxidant activities. In our preliminary experiments, different levels of spices (cumin, clove, and black pepper) were tested into a cheese matrix and only one level 0.2 g/100 g (0.2%) based on cheese weight was considered good after sensory evaluation. Findings of the present study revealed that ACE-inhibitory potential was the highest in processed cheese made from buffalo milk with the addition of 0.2% cumin, clove, and black pepper. A significant increase in ACE-inhibition (%) of processed cheddar cheese, as well as its WSE and ESE, was obtained. Lower IC50 values were found after duodenal phase digestion compared to oral phase digestion.

COVID-19 utilizes the ACE2 pathway as a means of infection. Early data on COVID-19 suggest heterogeneity in the severity of symptoms during transmission and infection ranging from no symptoms to death. The source of this heterogeneity is likely multifaceted and may have a genetic component. Demographic and clinical comorbidities associated with the severity of infection suggest that possible variants known to influence the renin-angiotensin-aldosterone (RAAS) system pathway (particularly those that influence ACE2) may contribute to the heterogenous infection response. ACE2 and Ang(1-7) (the product of ACE2) seem to have a protective effect on the pulmonary and cardiac systems. Hypertension medication modulation, may alter ACE2 and Ang(1-7), particularly in variants that have been shown to influence RAAS system function, which could be clinically useful in patients with COVID-19.

Food protein-derived hydrolysates with multi-bioactivities such as antihypertensive and antioxidant properties have recently received special attention since both activities can play significant roles in preventing cardiovascular diseases. This study reports, for the first time, the angiotensin I-converting enzyme (ACE)-inhibition and antioxidant properties of ultrafiltrate fractions (UF) with different molecular weight ranges (<1, 1-3 and ≥3 kDa) obtained from Fucus spiralis protein hydrolysate (FSPH) digested with cellulase-bromelain. The amino acids profile, recovery yield, protein, peptide and total phenolic contents of these FSPH-UF, and the in vitro digestibility of F. spiralis crude protein were also investigated. FSPH-UF ≥3 kDa presented remarkably higher ACE-inhibition, yield, peptide and polyphenolic (phlorotannins) contents. Antioxidant analysis showed that FSPH-UF <1 kDa and ≥3 kDa exhibited significantly higher scavenging of 2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion-chelating (FIC) activity. FSPH-UF ≥3 kDa had also notably higher ferric reducing antioxidant power (FRAP). Strong correlations were observed between ACE-inhibition and antioxidant activities (FIC and FRAP). The results suggest that ACE-inhibition and antioxidant properties of FSPH-UF may be due to the bioactive peptides and polyphenols released during the enzymatic hydrolysis. In conclusion, this study shows the potential use of defined size FSPH-UF for the prevention/treatment of hypertension and/or oxidative stress-related diseases.

This study aimed to investigate in vitro the health-promoting benefits (anticancer activity, α-amylase and α-glucosidase inhibition, angiotensin-converting-enzyme (ACE)-inhibition, antioxidant and proteolytic activity) of camel milk fermented with indigenous probiotic strains of Lactobacillus spp., compared with fermented bovine milk. The three camel milk probiotic strains Lb. reuteri-KX881777, Lb. plantarum-KX881772, Lb. plantarum-KX881779 and a control strain Lb. plantarum DSM2468 were employed to ferment camel and bovine milks separately. The proteolytic and antioxidant activity of water soluble extracts (WSEs) from all fermented camel milks were higher than those of fermented bovine milk. α-Amylase inhibition of WSEs were >34% in both milk types fermented with all strains during storage periods, except the WSE of camel milk fermented by Lp.K772. The highest ACE-inhibition of the WSE from camel milk fermented by Lr.K777 was >80%. The proliferations of Caco-2, MCF-7 and HELA cells were more inhibited when treated with the WSE of fermented camel milk.