Search Results (166)

Hypertension is a major pathogenic contributor to cardiovascular diseases, primarily mediated through activation of the angiotensin-converting enzyme (ACE) system. Food-derived ACE-inhibitory peptides represent a promising alternative to synthetic drugs due to their favorable safety profile and minimal side effects. ACE-inhibitory peptides have been extensively identified from various foods, with their antihypertensive activity and molecular mechanisms comprehensively characterized through in vitro and in vivo studies. ACE-inhibitory peptides can be prepared by methods such as natural extraction, enzymatic hydrolysis, and fermentation. The production process significantly modulates structural characteristics of the polypeptides including peptide chain length, amino acid composition, and sequence, consequently determining their functional activity. To comprehensively elucidate the gastrointestinal stability and mechanisms action of ACE-inhibitory peptides, integrated experimental approaches combining both in vitro and in vivo methodologies are essential. This review systematically examines current advances in food-derived ACE-inhibitory peptides in terms of sources, production, structure, in vivo and in vitro activities, and bioavailability. Full article

Aminopeptidase A (APA) cleaves a single aspartate residue from the amino terminus of peptides within the renin angiotensin system (RAS). Since several RAS peptides contain an N-terminal aspartate, we developed an assay to evaluate the effect of recombinant APA on the cleavage of Ang I, Ang II, Ang-(1-7), Ang-(1-9), and Ang-(1-12). The latter peptide has been proposed to be a functional Ang II-forming substrate with a hypertensive action attributable to the formed Ang II acting on AT1 receptors. Here we investigated the following: (a) the hydrolytic action of APA on Ang-(1-12), Ang I (1-10), Ang-(1-9), Ang II and Ang-(1-7) and (b) whether Ang-(1-12) pressor activity is altered by recombinant APA (r-APA) or genetic APA deficiency. We found that (a) r-APA cleaves the N-terminal aspartate of not only Ang II but also [Ang-(1-12), Ang I (1-10), Ang-(1-9)] and [Ang-(1-7)]; (b) the pressor activity of Ang-(1-12) was abolished in the presence of Lisinopril or Telmisartan; (c) r-APA significantly attenuated the pressor activities of infused Ang I and Ang II but not Ang-(1-12); and (d) r-ACE2 also did not attenuate the pressor effect of infused Ang-(1-12). Thus, in addition to increasing blood pressure indirectly via the formation of Ang II, Ang-(1-12) increases blood pressure by an Ang II-independent mechanism. We conclude that APA has an antihypertensive effect attributable to rapid degradation of Ang II, and this action may have a therapeutic potential in forms of hypertension that are Ang II-dependent. In addition, APA metabolizes Ang-(1-12), a peptide that has a prohypertensive action, in part, as a source of Ang II formation but also by a yet to be determined action independent of Ang II. Full article

Diuretics are a class of pharmacological agents that promote the renal excretion of water and electrolytes, increasing urine output and reducing fluid retention. They play a critical role in the management of edematous syndromes, irrespective of their etiology (cardiac, renal, or hepatic), as well as in the treatment of hypertension (HTA). The mechanism of action of diuretics can be classified as either renal, as seen with saluretic diuretics that inhibit sodium and water reabsorption at various segments of the nephron, or extrarenal, involving alterations in the glomerular filtration pressure or osmotic mechanisms. Based on their site of action and mechanism, diuretics are categorized into multiple classes, including loop diuretics, thiazide and thiazide-like diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, and osmotic diuretics. These agents are frequently used in combination with other antihypertensive or heart failure medications to optimize therapeutic efficacy. By reducing the blood volume and peripheral vascular resistance, diuretics improve cardiac function, lower blood pressure, and enhance exercise tolerance. Additionally, they are employed in managing chronic kidney disease (CKD), electrolyte imbalances, and specific metabolic disorders. Given the potential for adverse effects such as electrolyte disturbances and renal dysfunction, diuretic therapy should be individualized, with the careful monitoring of the dosage, patient response, and comorbid conditions. Patient education on adherence, lifestyle modifications, and the recognition of side effects is essential for optimizing the therapeutic outcomes and minimizing the risks associated with diuretic therapy. Full article

Pediatric obesity is associated with a wide range of comorbidities beyond metabolic changes, affecting cardiovascular, endocrine, reproductive, musculoskeletal systems, and also mental health. Hypertension, commonly observed in children with obesity, increases the risk of long-term cardiovascular disease. Polycystic ovary syndrome (PCOS) presents another significant endo-reproductive challenge that often develops during adolescence in females, leading to further comorbidities in adulthood. Additionally, excess adiposity can negatively impact bone health by modifying bone metabolism and increasing fracture risk. Obesity is also strongly linked to mental health disorders, including depression, anxiety, and low self-esteem, which can further exacerbate unhealthy lifestyle behaviors and disorders. Given the limitations and poor adherence of traditional treatment strategies, nutraceuticals have emerged as potential complementary therapies due to their bioactive properties. Various compounds have demonstrated antihypertensive, insulin-sensitizing, and anti-inflammatory effects, while others support bone metabolism and promote mental well-being. Herewith, we discuss the role of nutraceuticals in managing hypertension, PCOS, bone health, and mental health issues in individuals with obesity, evaluating their mechanisms of action and clinical relevance. Integrating nutraceutical compounds with dietary and lifestyle interventions may improve treatment outcomes and prevent obesity-related comorbidities. Further, we emphasize the need for further large-scale clinical studies, especially in pediatric patients. Full article

Systemic hypertension is a major global health concern, significantly contributing to the risk of cardiovascular, cerebrovascular, and renal diseases. Antihypertensive medications play a crucial role in lowering blood pressure, with diuretics serving as a particularly effective first-line therapy. However, the development of new compounds with diuretic properties, renal protective effects, and unique mechanisms of action remains a critical area of research for improving clinical outcomes. In this context, the present study investigated the diuretic and renal protective potential of the citrus flavonoid hesperidin in rats. Male spontaneously hypertensive and normotensive rats were treated with hesperidin at a dose of 3.0 mg/kg daily for seven days. Urine samples were analyzed for electrolytes (Na⁺, K⁺, Cl⁻, and Ca²⁺), biochemical parameters, and crystal precipitation, while renal tissues were examined histologically. Hesperidin treatment resulted in significant diuretic and natriuretic effects, along with potassium- and calcium-sparing properties. Furthermore, a marked reduction in calcium oxalate crystal formation was observed in the hesperidin-treated group. Histological analysis indicated a protective effect on renal tissue, with structural preservation observed in hypertensive rats. Docking studies revealed that hesperetin, the active metabolite of hesperidin formed upon oral administration, exhibited a high binding affinity for the calcium-sensing receptor (CaSR). This hypothesis may explain its role in preventing urinary crystalluria and contributing to calcium-sparing effects. Full article

Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, requiring both pharmacological and lifestyle-based preventive strategies. Artichoke (Cynara cardunculus L. var. scolymus) has gained attention for its health benefits, including choleretic and lipid-lowering activities. However, its cardiovascular effects remain underdiscussed. This paper provides a critical review of the current literature on the cardiovascular effects of artichoke, with a focus on its underlying mechanisms of action and clinical efficacy. Experimental studies assessing artichoke’s effects on endothelial function, vascular smooth muscle relaxation, and modulation of the renin–angiotensin–aldosterone axis were assessed. Additionally, clinical studies, systematic reviews, and meta-analyses investigating its antihypertensive effects were reviewed. Artichoke and its bioactive components, particularly flavonoids and caffeoylquinic acids, enhance endothelial-dependent and -independent vasorelaxation and inhibit angiotensin-converting enzyme activity. Although clinical studies indicate improvements in flow-mediated dilation, they report only modest reductions in blood pressure, with high variability in formulations, dosages, and patient populations. While artichoke supplementation may support blood pressure regulation and endothelial health, current evidence suggests it should be considered an adjunct rather than a replacement for conventional antihypertensive therapy. Standardized formulations and well-controlled clinical studies will be required to clarify its therapeutic role. Full article

The marine environment, covering over 70% of the Earth’s surface, serves as a reservoir of bioactive molecules, including peptides and proteins. Due to the unique and often extreme marine conditions, these molecules exhibit distinctive structural features and diverse functional properties, making them promising candidates for therapeutic applications. Marine-derived bioactive peptides, typically consisting of 3 to 40 amino acid residues—though most commonly, 2 to 20—are obtained from parent proteins through chemical or enzymatic hydrolysis, microbial fermentation, or gastrointestinal digestion. Like peptides, protein hydrolysates from collagen, a dominant protein of such materials, play an important role. Peptide bioactivities include antioxidant, antihypertensive, antidiabetic, antimicrobial, anti-inflammatory, anticoagulant, and anti-cancer effects as well as immunoregulatory and wound-healing activities. These peptides exert their effects through mechanisms such as enzyme inhibition, receptor modulation, and free radical scavenging, among others. Fish, algae, mollusks, crustaceans, microbes, invertebrates, and marine by-products such as skin, bones, and viscera are some of the key marine sources of bioactive proteins and peptides. The advancements in the extraction and purification processes, e.g., enzymatic hydrolysis, ultrafiltration, ion-exchange chromatography, high-performance liquid chromatography (HPLC), and molecular docking, facilitate easy identification and purification of such bioactive peptides in greater purity and activity. Despite their colossal potential, their production, scale-up, stability, and bioavailability are yet to be enhanced for industrial applications. Additional work needs to be carried out for optimal extraction processes, to unravel the mechanisms of action, and to discover novel marine sources. This review emphasizes the enormous scope of marine-derived peptides and proteins in the pharmaceutical, nutraceutical, cosmeceutical, and functional food industries, emphasizing their role in health promotion and risk reduction of chronic diseases. Full article

The prevalence of hypertension is increasing worldwide, in particular in developing countries. Anti-hypertensive drugs are commonly used to treat hypertension. However, in developing countries, where access to health care is scarce and the supply system is poor, anti-hypertensive drugs may not always be available. Moringa oleifera is a plant widely found in developing countries, with its leaves, seeds, flowers, roots, and pods used both for nutritional purposes and in traditional medicine to treat various diseases, including hypertension. This review summarizes the evidence, both in animal and human models, about the antihypertensive effects of different parts of M. oleifera, discusses possible mechanisms of action, explores its bioactive compounds with potential antihypertensive properties, and highlights the limitations of its use as a hypotensive agent. Many preclinical studies attribute antihypertensive properties to M. oleifera, particularly the leaves. However, it is premature to draw firm conclusions, as there is a great lack of randomized controlled trials demonstrating its real efficacy. The mechanisms of action and the compounds responsible for the hypotensive effect have not yet been fully elucidated. Therefore, further clinical trials showing its efficacy are strongly required before promoting Moringa for therapeutic purposes. At present, Moringa remains a plant with nutritional and pharmacological potential. Full article

The genus Allium contains more than 300 species where garlic, onion and leek can be found. Recent studies highlight the potential of phytochemicals present in the genus Allium as therapeutic agents, such as antimicrobial, antihypertensive, antioxidant and antiinflammatory, which makes it a widely studied genus and an attractive option for both the pharmaceutical and food industries. This review aims to explore the current knowledge in this field. It highlights key findings regarding the pharmacological approach on thiosulfinates and polysulfides for Allium sativum, Allium ampeloprasum and Allium sphaerocephalon species. Further, by integrating what has been reported in previous research, this review proposes an action mechanism for the formation of thiosulfinates and polysulfides, which will help harness the therapeutic potential of nature-inspired solutions in combating illness. Full article

Background: Sweet almond expeller is an abundant protein resource, but there are few studies on multifunctional peptides. The purpose of this study is to improve its application in food and medical industries. Methods: This study investigated the identification, screening, and action mechanisms of antihypertensive peptides with antioxidant and ferrous binding activities derived from sweet almond globulin hydrolysates using intergrade in vitro and in silico methods and an animal model. Results: Eight novel oligopeptides were identified in sweet almond globulin hydrolysates subfraction D; of them, Pro-Met-Tyr-Gly-Gly-Gly-Met-Val (PMYGGGMV) exhibited ACE inhibitory activity (IC₅₀: 121.16 μmol/L), ferrous binding ability (11.01 mg/g), and quenching capacities on hydroxyl (93.06%) and ABTS radicals (83.67%). The phenolic hydroxyl, amino, and carboxyl groups of PMYGGGMV were linked to Lys511, Tyr520, and Tyr523 in ACE’s substrate binding center through four short hydrogen bonds. PMYGGGMV can inhibit the Kelch-like ECH-Associated Protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) interaction by binding to seven residues of Keap1 (including a key residue, Arg415). The ACE inhibitory and antioxidant activities of PMYGGMY were stable during gastrointestinal digestion. Ferrous chelation did not alter the ACE inhibitory and antihypertensive effects of PMYGGMY, but it reduced its ABTS and hydroxyl radical scavenging ability (p < 0.05). Additionally, PMYGGGMV reduced blood pressure of spontaneous hypertension rates and improved iron absorption across Caco-2 cells (p < 0.05). Conclusions: PMYGGGMV has the potential to prevent oxidative stress, hypertension, and iron deficiency. Full article

Valerian possesses a multitude of pharmacological effects, including sedative and hypnotic properties, antihypertensive effects, antibacterial activity, and liver protection. Insomnia, one of the most prevalent disorders in contemporary society, significantly impacts people’s daily lives. This study aims to explore the anti-insomnia effects of valerian volatile oil (VVO) and investigate its potential mechanism of action through chemical analysis, network pharmacology, molecular docking, molecular dynamics simulations, and experimental validation. Through gas chromatography–mass spectrometry (GC-MS) analysis and drug-likeness screening, we identified 38 active compounds. Network pharmacology studies revealed that these 38 compounds might affect 103 targets associated with insomnia, such as monoamine oxidase B (MAOB), dopamine receptor D2 (DRD2), monoamine oxidase A (MAOA), interleukin 1β (IL1B), solute carrier family 6 member 4 (SLC6A4), prostaglandin-endoperoxide synthase 2 (PTGS2), and 5-hydroxytryptamine receptor 2A (HTR2A), which contribute to regulating the neuroactive ligand–receptor interaction, 5-hydroxytryptaminergic synapse, and calcium signaling pathways. The results of the molecular dynamics simulations indicated that bis[(6,6-dimethyl-3-bicyclo[3.1.1]hept-2-enyl)methyl] (E)-but-2-enedioate exhibited a stabilizing interaction with MAOB. The animal studies demonstrated that gavage administration of a high dose (100 mg/kg) of VVO significantly diminished autonomous activity, decreased sleep latency, and extended sleep duration in mice. Furthermore, the results of the Western blot experiment indicated that VVO interacts with MAOB, resulting in decreased expression levels of MAOB in the cerebral cortex. This study demonstrates the protective mechanism of VVO against insomnia through chemical analysis, network pharmacology, and experimental validation and extends the possible applications of VVO, which is a potential therapeutic ingredient for use in insomnia treatment. Full article

Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and European Traditional Medicine) for the treatment of a wide range of disorders. Plants are a rich source of diverse phytoconstituents with antidiabetic, anticancer, antimicrobial, antihypertensive, antioxidant, antihyperlipidemic, cardioprotective, immunomodulatory, and/or anti-inflammatory activities. This review focuses on the 35 plants most commonly reported for the treatment of these major disorders, with a particular emphasis on their traditional uses, phytoconstituent contents, pharmacological properties, and modes of action. Active phytomolecules with therapeutic potential include cucurbitane triterpenoids, diosgenin, and limonoids (azadiradione and gedunin), which exhibit antidiabetic properties, with cucurbitane triterpenoids specifically activating Glucose Transporter Type 4 (GLUT4) translocation. Capsaicin and curcumin demonstrate anticancer activity by deactivating NF-κB and arresting the cell cycle in the G2 phase. Antimicrobial activities have been observed for piperine, reserpine, berberine, dictamnine, chelerythrine, and allitridin, with the latter two triggering bacterial cell lysis. Quercetin, catechin, and genistein exhibit anti-inflammatory properties, with genistein specifically suppressing CD8+ cytotoxic T cell function. Ginsenoside Rg1 and ginsenoside Rg3 demonstrate potential for treating cardiovascular diseases, with ginsenoside Rg1 activating PPARα promoter, and the PI3K/Akt pathway. In contrast, ternatin, tannins, and quercitrin exhibit potential in gastrointestinal disorders, with quercitrin regulating arachidonic acid metabolism by suppressing cyclooxygenase (COX) and lipoxygenase activity. Further studies are warranted to fully investigate the clinical therapeutic benefits of these plants and their phytoconstituents, as well as to elucidate their underlying molecular mechanisms of action. Full article

Our previous research demonstrated the health benefits of sericin-derived oligopeptides (SDOs) from yellow silk cocoons, particularly their hypoglycemic and antihypertensive properties. This study aims to produce SDOs at a pilot scale, preparing them for large commercial production as a novel food ingredient, and investigates the impact of scale-up on their characteristics and specifications. We compared the productivity of SDOs generated from 25 L and 300 L batches via the hydrolysis of sericin using 5% Neutrase (E/S) at 50 °C for 4 h. The 300 L production scale outperformed the 25 L scale, achieving a hydrolysis degree (DH) of 8.63%, a solid recovery rate of 94.35%, and enhanced inhibitory actions for dipeptidyl peptidase IV (DPP-IV) and angiotensin-converting enzyme (ACE). The characterization of peptides was carried out in ultrafiltered SDOs. Peptides < 3 kDa demonstrated optimal enzyme inhibition and were then fractionated by size exclusion chromatography into nine distinct fractions. Of the nine fractions, F1, F8, and F9 had significant enzyme inhibitory activity. LC-MS/MS analysis revealed 32 unique peptide sequences, with YPDLPYH exhibiting significant dual inhibitory effects on both DPP-IV (IC₅₀ 1.35 mM) and ACE (IC₅₀ 18.10 μM). The maximum residue limit (MRL) for trace metals, pesticide residues, and microbiological contamination in SDOs complies with food regulations. SDOs exhibited stability at 4, 25, and 45 °C for six months, based on their physical characteristics and biological activity. Considering their investigated characteristics, SDOs could be manufactured at a pilot capacity and used as a functional food component in commercial applications designed to improve metabolic health. Full article

Food protein-derived antihypertensive peptides have attracted substantial attention as a safer alternative for drugs. The regulation of the renin–angiotensin system (RAS) is an essential aspect underlying the mechanisms of antihypertensive peptides. Most of the identified antihypertensive peptides exhibit the angiotensin-converting enzyme (ACE) inhibitory effect. In addition, artificial intelligence has improved the efficiency of ACE inhibitory peptide identifications. Moreover, the inhibition of renin and blockade or down-regulation of angiotensin type I receptor (AT1R) have also been demonstrated to be effective intervention strategies. With the identification of the ACE2/Ang (1–7)/MasR axis, activation or up-regulation of angiotensin-converting enzyme 2 (ACE2) has also emerged as a new intervention pathway. This review summarizes the research progress of antihypertensive peptides in intervening with hypertension from the perspective of their properties, sources, and key factors. The objective of this review is to provide theoretical references for the development of antihypertensive peptides and the explorations of the molecular mechanisms. Full article

Fruits are excellent sources of substrate for various fermented products, including fruit vinegars, which are typically produced by submerged fermentation. Some evidence suggests that fruit vinegar consumption can alleviate certain disorders, including hyperlipidemia, inflammation, and hyperglycemia. Fruit vinegars also have bacteriostatic and antihypertensive actions. Recent studies also suggest that apple vinegar may offer benefits in treating insulin resistance, osteoporosis, and certain neurological diseases such as Alzheimer’s disease; it may also support weight loss. Recent studies in animal and human models have considerably broadened our understanding of the biological properties of not only fruit vinegars but also oxymels, i.e., mixtures of vinegar and honey or sugar. This paper reviews the current state of knowledge regarding vinegars and oxymels, with a special emphasis on their chemical composition and the mechanisms behind their biological activity and pro-health potential. The multidirectional effects of fruit vinegars and oxymels result from the synergy of different chemical compounds, including organic acids (mainly acetic acid), phenolic compounds, vitamins, minerals, and fermentation products. However, more studies are needed to understand the interactions between all the different components, not only the phenolic compounds and organic acids. In addition, more research is needed on their mechanisms of action. Although no serious side effects have been noted to date, further studies with large sample sizes are needed to understand the possible side effects of long-term fruit vinegar and oxymel use. Full article