Antihypertensive Properties Research Articles

Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases.

In recent decades, as a result of rising mortality rates due to cardiovascular diseases (CVDs), there has been a growing urgency to find alternative approaches to conventional pharmaceutical treatment to prevent the onset of chronic diseases. Arthrospira platensis, commonly known as Spirulina, is a blue-green cyanobacterium, classified as a "superfood", used worldwide as a nutraceutical food supplement due to its remarkable nutritional value, lack of toxicity, and therapeutic effects. Several scientific studies have evaluated the cardioprotective role of Spirulina. This article presents a comprehensive review of the therapeutic benefits of Spirulina in improving cardio- and cerebrovascular health. It focuses on the latest experimental and clinical findings to evaluate its antihypertensive, antidiabetic, and antihyperlipidemic properties. The objective is to highlight its potential in preventing and managing risk factors associated with cardiovascular disease (CVD).

Quercetin, a Flavonoid with Great Pharmacological Capacity.

Quercetin is a flavonoid with a low molecular weight that belongs to the human diet's phenolic phytochemicals and nonenergy constituents. Quercetin has a potent antioxidant capacity, being able to capture reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive chlorine species (ROC), which act as reducing agents by chelating transition-metal ions. Its structure has five functional hydroxyl groups, which work as electron donors and are responsible for capturing free radicals. In addition to its antioxidant capacity, different pharmacological properties of quercetin have been described, such as carcinostatic properties; antiviral, antihypertensive, and anti-inflammatory properties; the ability to protect low-density lipoprotein (LDL) oxidation, and the ability to inhibit angiogenesis; these are developed in this review.

Scopoletin: a review of its pharmacology, pharmacokinetics, and toxicity.

Scopoletin is a coumarin synthesized by diverse medicinal and edible plants, which plays a vital role as a therapeutic and chemopreventive agent in the treatment of a variety of diseases. In this review, an overview of the pharmacology, pharmacokinetics, and toxicity of scopoletin is provided. In addition, the prospects and outlook for future studies are appraised. Scopoletin is indicated to have antimicrobial, anticancer, anti-inflammation, anti-angiogenesis, anti-oxidation, antidiabetic, antihypertensive, hepatoprotective, and neuroprotective properties and immunomodulatory effects in both in vitro and in vivo experimental trials. In addition, it is an inhibitor of various enzymes, including choline acetyltransferase, acetylcholinesterase, and monoamine oxidase. Pharmacokinetic studies have demonstrated the low bioavailability, rapid absorption, and extensive metabolism of scopoletin. These properties may be associated with its poor solubility in aqueous media. In addition, toxicity research indicates the non-toxicity of scopoletin to most cell types tested to date, suggesting that scopoletin will neither induce treatment-associated mortality nor abnormal performance with the test dose. Considering its favorable pharmacological activities, scopoletin has the potential to act as a drug candidate in the treatment of cancer, liver disease, diabetes, neurodegenerative disease, and mental disorders. In view of its merits and limitations, scopoletin is a suitable lead compound for the development of new, efficient, and low-toxicity derivatives. Additional studies are needed to explore its molecular mechanisms and targets, verify its toxicity, and promote its oral bioavailability.

A high-quality chromosomal-level reference genome of Dendrobium nobile Lindl. provides new insights into the biosynthesis and accumulation of picrotoxane-type sesquiterpenoid alkaloids

Dendrobium nobile L., renowned for its ornamental and medicinal attributes, holds significant economic value attributed to its distinct biochemical constituents. A pivotal element within this plant, picrotoxane-type sesquiterpenoid alkaloids (PSAs), exhibits noteworthy anti-hypertensive, anti-cancer, analgesic, and antipyretic properties. However, research on understanding the genes involved in PSAs biosynthesis in D. nobile is very limited. This study provides a quality-enhanced 1.19-Gb genome of D. nobile, featuring a contig N50 of 10.01 Mb, located on 19 chromosomes and encompassing 31,672 protein-coding genes. A comparative genomic analysis reveals expanded gene families within D. nobile, and the implications of these expanded families on the biosynthesis of secondary metabolites were further considered. By incorporating a multifaceted analysis, including researches on gene expansion, tandem duplication, phylogeny, and gene clusters, incorporating the transcriptomics data based on four different expression profiles in D. nobile, the critical candidate genes involved in PSAs biosynthesis were successfully identified. Further implementation of weighted gene co-expression network analysis allowed the identification of 10 transcription factors as potential regulators during PSAs biosynthesis. This study provides valuable insights and genomics resources to elucidate further the evolution and biosynthesis of specialized PSAs, specifically dendrobine.

Oral Administration of Fermented Milk from Co-Starter Containing Lactobacillus plantarum Y44 Shows an Ameliorating Effect on Hypertension in Spontaneously Hypertensive Rats.

Fermented dairy foods such as yogurt exhibit some beneficial effects on consumers, including relieving the symptoms of hypertension. This study aims to obtain fermented dairy products from a co-starter that have a great flavor and the auxiliary function of reducing blood pressure after longtime consumption. Commercial starter cultures composed of Lactobacillus delbrueckii subsp. bulgaricus CICC 6047 and Streptococcus thermophilus CICC 6038 were combined with Lactobacillus plantarum strains Y44, Y12, and Y16, respectively, as a combined starter culture to ferment the mixed milk of skim milk and soybean milk. The fermented milk produced using the combined starter culture mixed with L. plantarum Y44 showed an angiotensin-converting-enzyme (ACE) inhibitory activity (53.56 ± 0.69%). Some peptides that regulate blood pressure were released in the fermented milk, such as AMKPWIQPK, GPVRGPFPII, LNVPGEIVE, NIPPLTQTPV, and YQEPVL. In spontaneously hypertensive rat (SHR) oral-administration experiments compared with the gavage unfermented milk group, the gavage feeding of SHRs with the fermented milk produced using the combined starter culture mixed with L. plantarum Y44 significantly reduced the blood pressure of the SHRs after long-term intragastric administration, shown with the systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreasing by 23.67 ± 2.49 mmHg and 15.22 ± 2.62 mmHg, respectively. Moreover, the abundance of short-chain fatty acids (SCFA), bacterial diversity in the gut microbiota, and SCFA levels including acetic acid, propionic acid, and butyric acid in the feces of the SHRs were increased via oral administration of the fermented milk produced using the combined starter culture containing L. plantarum Y44. Furthermore, the ACE-angiotensin II (Ang II)-angiotensin type 1 (AT 1) axis was downregulated, the angiotensin-converting-enzyme 2 (ACE 2)-angiotensin(1-7) (Ang1-7)-Mas receptor axis of the SHRs was upregulated, and then the RAS signal was rebalanced. The fermented milk obtained from the combined starter culture shows the potential to be a functional food with antihypertension properties.

Use of Various Sugarcane Byproducts to Produce Lipid Extracts with Bioactive Properties: Physicochemical and Biological Characterization.

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.

Phytochemical Profile, Acute Toxicity, Antioxidant and Anti-inflammatory Activity of Hydroethanolic Extracts from Odontonema strictum (Nees) Kuntze (Acanthaceae) Root and Stem

Background: The leaves of Odontonema strictum (Nees) Kuntze (Acanthaceae), a decorative plant native to Latin America, are used to treat hypertension in alternative medicine. However, the other parts of the plant have not yet been investigated for their antihypertensive properties. Aims: Our study aimed to investigate phytochemical groups with antihypertensive potential, antioxidant and anti-inflammatory properties, and the safety of using stems and roots hydroethanolic extracts.
 Methodology: Phytochemical screening by HPTLC and determining flavonoids and total polyphenols were carried out. The antioxidant activity was evaluated using ABTS, FRAP, DPPH, and LPO methods. The inhibitory activity of Phospholipase A2 and 15-lipoxygenase was determined. Finally, acute oral toxicity was carried out on female mice NMRI.
 Results: The hydroethanolic extracts of Odontonema strictum root (HE_ROS) and stem (HE_SOS) contain tannins, sterols, triterpenes, flavonoids, and saponosides. HE_SOS gave the highest levels of flavonoids (23.69±1.10 mg QE/g) and total phenolics (64.15±4.02 mg TAE/g. The two hydroethanolic extracts had antioxidant activity, with HE_ROS being the best. However, these activities were lower than Trolox (p<0.05). The extracts have a moderate inhibitory effect on 15-lipoxygenase and Phospholipase A2. Finally, HE_ROS and HE_SOS are practically non-toxic when administered once orally.
 Conclusion: This study provided scientific data and could justify the use of Odontonema strictum in the treatment of hypertension.

Exploring the Therapeutic Potential: Phytochemistry and Pharmacology of Bryophyllum pinnatum

Bryophyllum pinnatum, a renowned medicinal plant with a rich history in various traditional medical practices, has been utilized for treating a range of ailments such as fever, smallpox, otitis, cough, asthma, headache, convulsion, and general debility. The plant's diverse secondary metabolites, including steroids, flavonoids, terpenoids, fatty acids, bufadienolides, proteins, peptides, vitamins, and polysaccharides, have been identified. Over the past thirty years, extensive research has unveiled the plant's pharmacological effects both in vivo and in vitro, demonstrating its antimicrobial, anti-ulcer, antihypertensive, antileishmanial, anti-cancer, antidiabetic, and immunomodulatory properties.
 This comprehensive review aims to provide a consolidated overview of Bryophyllum pinnatum, encompassing its traditional uses, phytochemistry, and pharmacological studies. By presenting a wealth of information, this paper seeks to inspire further exploration into the potential beneficial applications of the plant. Additionally, it sheds light on the clinical uses and prospects of Bryophyllum pinnatum, offering valuable insights for future research endeavors.
 Keywords: Bryophyllum pinnatum, Chemical Constituent, Biological activities, antioxidant effect, Therapeutic potential

From Hypertension to Beyond: Unraveling the Diverse Mechanisms of Olmesartan in Disease Modulation.

Olmesartan, originally known for its antihypertensive properties, exhibits promising potential in addressing inflammation-mediated diseases. As an angiotensin II receptor blocker (ARB), Olmesartan influences pivotal pathways, including reactive oxygen species, cytokines, NF-κB, TNF-α, and MAPK. This suggests a viable opportunity for repurposing the drug in conditions such as ulcerative colitis, neuropathy, nephropathy, and cancer, as supported by multiple preclinical studies. Ongoing clinical trials, particularly in cardiomyopathy and nephropathy, suggest a broader therapeutic scope for Olmesartan. Repurposing efforts would entail comprehensive investigations using disease-specific preclinical models and dedicated clinical studies. The drug's established safety profile, wide availability, and well-understood ARB mechanism of action offer distinct advantages that could facilitate a streamlined repurposing process. In summary, Olmesartan's versatile impact on inflammation-related pathways positions it as a promising candidate for repurposing across various diseases. Ongoing clinical trials and the drug's favorable attributes enhance its appeal for further exploration and potential application in diverse medical contexts.

The Use of Nigella sativa in Cardiometabolic Diseases.

Nigella sativa L. is an herb that is commonly used in cooking and in traditional medicine, particularly in Arab countries, the Indian subcontinent, and some areas of eastern Europe. Nigella sativa is also called "black cumin" or "black seeds", as the seeds are the most-used part of the plant. They contain the main bioactive component thymoquinone (TQ), which is responsible for the pleiotropic pharmacological properties of the seeds, including anti-oxidant, anti-inflammatory, anti-hypertensive, anti-hepatotoxic, hypoglycemic, and lipid-lowering properties. In this narrative review, both the potential mechanisms of action of Nigella sativa and the fundamental role played by pharmaceutical technology in optimizing preparations based on this herb in terms of yield, quality, and effectiveness have been outlined. Moreover, an analysis of the market of products containing Nigella sativa was carried out based on the current literature with an international perspective, along with a specific focus on Italy.

Therapeutic potential of oleanolic acid in liver diseases.

Liver-associated diseases affect millions of individuals worldwide. In developed countries, the incidence of viral hepatitis is reducing due to advancements in disease prevention, diagnosis, and treatment. However, with improvements in living standards, the prevalence of metabolic liver diseases, such as non-alcoholic fatty liver disease and alcohol-related liver disease, is expected to increase; notably, this rise in the prevalence of metabolic liver disease can lead to the development of more severe liver diseases, including liver failure, cirrhosis, and liver cancer. The growing demand for natural alternative therapies for chronic diseases has highlighted the importance of studying the pharmacology of bioactive compounds in plants. One such compound is oleanolic acid (OA), a pentacyclic triterpenoid known for its antioxidant, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, anti-diabetic, cardioprotective, hepatoprotective, and anti-neurodegenerative properties. Recent studies have demonstrated that OA treatment can reduce the risk of pathological liver damage, ultimately alleviating liver dysregulation and restoring overall liver function. This review aims to explore the latest research on the biological effects of OA and its derivatives. Notably, it explores the mechanisms of action of these compounds in both in vitro and in vivo research models and, ultimately, highlights OA as a promising candidate for alternative therapies in the treatment and management of chronic liver disease.

In vitro evaluation of the anti-hypertensive potential of albumin and globulin hydrolysates from cocoa bean (Theobroma cacao L. var. Forastero)

According to reports from the World Health Organization (WHO), hypertension is considered the most common cardiovascular risk factor, affecting 25 to 30% of the world's population. One of the primary causes of hypertension is angiotensin-converting enzyme-I (ACE), which plays a crucial role in regulating blood pressure through the modulation of the renin-angiotensin-aldosterone system. Consequently, there is a wide range of drugs available that can inhibit ACE. However, these drugs can cause adverse side effects such as cough, headache, skin rash, altered taste, angioedema, nausea, and allergic reactions. For this reason, there is considerable interest in obtaining ACE inhibitors from natural sources that reduce side effects and dependence on drugs. Specifically, bioactive peptides present in enzymatic protein hydrolysates have shown anti-hypertensive properties by inhibiting ACE, making them a promising alternative in the prevention and treatment of hypertension. The objective of this study was to evaluate the ACE inhibitory activity (in vitro) of enzymatic hydrolysates obtained from cocoa bean proteins (albumin and globulin), with the purpose of considering them as a natural source of potential anti-hypertensive agents. The results demonstrated that the enzymatic treatment (with alcalase) of albumin and globulin from cocoa beans is a viable bioprocess for producing hydrolysates with ACE inhibitory activity. In particular, hydrolysates and peptide fractions (< 3000 Da) with greater ACE inhibitory capacity were generated from globulin, making them a suitable choice for designing functional foods.

Telmisartan-loaded liposomes: An innovative weapon against breast cancer

This study focuses on the development of a liposomal preparation for the targeted delivery of Telmisartan in the context of breast cancer treatment. Telmisartan, a pharmaceutical agent with potential anticancer properties, has been encapsulated within liposomes, lipid-based vesicles known for their capacity to enhance drug delivery and improve therapeutic outcomes. The formulation and characterization of Telmisartan-loaded liposomes were conducted, evaluating factors such as size, shape, and drug release profiles. The findings demonstrate that the liposomal preparation effectively encapsulates Telmisartan, maintaining its pharmacological properties. The development of such liposomal formulations holds promise for advancing breast cancer therapies, offering the potential for enhanced treatment efficacy and reduced side effects. This research contributes to the ongoing efforts to explore innovative drug delivery strategies in the realm of breast cancer treatment. Breast cancer is a pervasive and challenging malignancy affecting women worldwide. In the quest for more effective and targeted treatment approaches, the development of liposomal preparations for delivering therapeutic agents to breast cancer cells has emerged as a promising avenue. Telmisartan, originally recognized for its antihypertensive properties, has been increasingly investigated for its potential anticancer effects. This study delves into the design and evaluation of a liposomal formulation for Telmisartan, aiming to enhance its therapeutic potential in breast cancer. The formulation process involved the encapsulation of Telmisartan within lipid-based liposomes, which are well-known for their ability to carry a variety of drugs, protect them from degradation, and enhance their selective delivery to tumor cells.

Antioxidative, Metabolic and Vascular Medicinal Potentials of Natural Products in the Non-Edible Wastes of Fruits Belonging to the Citrus and Prunus Genera: A Review.

Diabetes mellitus and related metabolic and vascular impairments are notable health problems. Fruits and vegetables contain phenolics that are beneficial to metabolic and oxidative health and useful in preventing associated disease. Scientific evidence has shown that some bioactive phenolics are more abundant in the non-edible parts (especially the peels) of many fruits than in their respective edible tissues. Fruits belonging to the Citrus and Prunus genera are commonly consumed worldwide, including in South Africa, and their non-edible wastes (peel and seed) have been shown to have antioxidative, metabolic and vascular pharmacological potentials and medicinal phytochemistry. It is therefore imperative to evaluate the pharmacological actions and phytochemical properties of the non-edible wastes of these fruits and understand how they could potentially be of medicinal relevance in oxidative, metabolic and vascular diseases, including diabetes, oxidative stress, obesity, hypertension and related cardiovascular impairments. In the absence of a previous review that has concomitantly presented the medicinal potentials of fruits wastes from both genera, this review presents a critical analysis of previous and recent perspectives on the medicinal potential of the non-edible wastes from the selected Citrus and Prunus fruits in metabolic, vascular and oxidative health. This review further exposes the medicinal phytochemistry, while elucidating the underlying mechanisms through the fruit wastes potentiates their therapeutic effects. A literature search was carried out on "PubMed" to identify peer-reviewed published (mostly 2015 and beyond) studies reporting the antidiabetic, antioxidative, antihypertensive, anti-hyperlipidemic and anti-inflammatory properties of the non-edible parts of the selected fruits. The data of the selected studies were analyzed to understand the bioactive mechanisms, bioactive principles and toxicological profiles. The wastes (seed and peel) of the selected fruits had antioxidant, anti-obesogenic, antihypertensive, anti-inflammatory, antidiabetic and tissue protective potentials. Some phenolic acids and terpenes, as well as flavonoids and glycosides such as narirutin, nobiletin, hesperidin, naringin, naringenin, quercetin, rutin, diosmin, etc., were the possible bioactive principles. The peel and seed of the selected fruits belonging to the Citrus and Prunus genera are potential sources of bioactive compounds that could be of medicinal relevance for improving oxidative, metabolic and vascular health. However, there is a need for appropriate toxicological studies.

Effects of diets supplemented with bioactive peptides on nutrient digestibility, immune cell responsiveness, and fecal characteristics, microbiota, and metabolites of adult cats.

Bioactive peptides (BP) are recognized for their ability to function as antioxidants and maintain lipid stability. They may have positive health effects, including antihypertensive, anti-inflammatory, antimicrobial, osteoprotective, gut health, and immunomodulatory properties, but are poorly tested in cats. Our primary objective was to determine the apparent total tract digestibility (ATTD) of BP-containing kibble diets and assess how the fecal characteristics, metabolites, and microbiota were affected in adult cats. Our secondary objective was to test whether BP could impact blood oxidative stress markers and cytokine concentrations following transport stress. Twelve adult cats (4.83±0.37 yr; 4.76±0.14kg) were used in a replicated 4×4 Latin square design to test four extruded kibble diets: Control (no BP), Chicken (4% chicken BP), Marine1 (2% marine BP), and Marine2 (4% marine BP). Each experimental period lasted 28 d, with a 20-d adaptation phase, 5 d for fecal collection, 2 d for blood collection, and 1 d for transport stress testing (driven in vehicle in individual carriers for 45min). Salivary cortisol and blood oxidative stress markers and cytokines were measured after transport. Fecal microbiota data were evaluated using 16S rRNA gene amplicon sequencing and QIIME2. All other data were analyzed using the Mixed Models procedure of SAS, with P<0.05 being considered significant and P<0.10 considered trends. No differences were observed in animal health outcomes, with all cats remaining healthy and serum metabolites remaining within reference ranges. Cats fed the Marine2 diet had higher (P<0.05) ATTD of dry matter (84.5% vs. 80.9%) and organic matter (88.3% vs. 85.8%) than those fed the control diet. The ATTD of protein and energy tended to be higher (P<0.10) for cats fed the Marine2 diet. Fecal characteristics, metabolites, and bacterial alpha and beta diversity measures were not affected by treatment. However, the relative abundances of six bacterial genera were different (P<0.05) and two bacterial genera tended to be different (P<0.10) across treatments. Treatment did not alter salivary cortisol, blood oxidative stress markers, or blood cytokines after transport stress. Our data suggest that BP inclusion may increase nutrient digestibility and modify fecal microbiota and immune measures. More testing is required, however, to determine whether BP may provide additional benefits to cats.

Antihypertensive efficacy and safety of azilsartan medoxomil in patients with diabetes mellitus in real clinical practice. According to the CONSTANT study

Background. Obesity and associated diseases are the most common comorbidities in patients with arterial hypertension (AH). The combination of AH and type 2 diabetes mellitus (DM2) significantly exacerbates the cardiovascular risk in this patients. BP control is one of the key components of the multivariate approach to reducing the risk of DM 2 complications. The use of drugs with pronounced antihypertensive properties and at the same time the ability to improve metabolic parameters should be a priority in this category of patients. Assessing the efficacy and safety of azilsartan medoxomil, the last molecule from the ARB class in patients with AH and DM 2 is an urgent task.Purpose. Evaluation of antihypertensive efficacy and safety of azilsartan medoxomil in patients with AH and DM 2 and overweight or obesity.Materials and methods. 235 overweight or obese patients with AH and DM2 enrolled in the international multicenter observational non-interventional prospective study CONSTANT with azilsartan medoxomil according to the approved label. The observation period is 6 months.Results. The dynamics of SBP by visit 4 (6 months) was 29,7±14,5 mmHg, DBP - 13,36±10,9 mmHg (r≤0,001). Overall, the group achieved BP targets in 211 (89.41%) DM patients enrolled in the study. Response to therapy (reduction in SBP by at least 20 mmHg, DBP of 10 mm Hg) was obtained in 177 (75.0%) patients. Glycated hemoglobin (p&lt;0.001) and fasting glucose (p&lt;0.001) significantly decreased in patients with AH and DM. A decrease in total cholesterol, triglycerides, and LDL was observed, including in DM patients not taking statins (p&lt;0.001). Overall, a decrease in waist circumference was observed across the group (p&lt;0.005).Conclusion. Azilsartan medoxomil in real clinical practice proved to be a highly effective antihypertensive drug in patients with AH and DM. The ability of the drug, including in combination with other drugs, to improve the metabolic profile, reduce the volume of adipose tissue makes it a priority drug of choice in patients with AH, obesity and type 2 DM.

ANTIHYPERTENSIVE AND ANTIDIABETIC PEPTIDES DERIVED FROM IN SILICO SIMULATED GASTROINTESTINAL DIGESTION OF QUINOA (Chenopodium quinoa) GLOBULINS AND MOLECULAR DOCKING STUDY

This study evaluated the impact of in silico simulated gastrointestinal digestion (GID) of four quinoa globulins on the potential to release ACE and DPP-IV inhibitor peptides (antihypertensive and antidiabetic properties, respectively), as well as performed a molecular docking study to evaluate the interactions produced in the peptide-enzyme complexes. In silico GID performed on quinoa globulins resulted in the formation of amino acids as well as peptides with two to five residues. The peptides PSF, IPG, CSG, SPR, CSPG and PPN stood out for their high bioactivity scores (&gt; 0.6), for not showing toxicity, as well as presenting potential inhibitory properties to both ACE and DPP-IV enzymes evaluated by ToxinPred, PeptideRanker and BioPep tools, respectively. The molecular docking analysis allowed highlighting that all peptides interacted with the enzymes, finding favorable binding energy values, different number and type of interactions, either at the level of the enzyme active sites or not, characteristics that together would define the potential of the established interaction of the complexes formed. The results, at the level of a first screening, support that GID of quinoa globulins can give rise to peptides with both antihypertensive and antidiabetic properties, requiring further in vitro and in vivo studies.

Tetrandrine inhibits aldosterone synthesis by covalently targeting CYP11A1 to attenuate hypertension.

Tetrandrine (Tet) is the main pharmacological component of Stephania tetrandra S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses in vivo and in vitro. The diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats. Tet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis. This study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.

Underutilized Canadian wild berries as potential sources of lipophilic bioactive compounds with antihypertensive properties.

Traditional berries are small fruits and are widely distributed in the Canadian prairies. The current study investigates the lipophilic bioactive compounds such as fatty acids, phytosterols, and terpenes, and their bioactivities, such as lipid peroxidation, as well as the antihypertensive activities of fourteen underutilized Canadian wild berries. These berries include Saskatoon berries (Amelanchier alnifolia), gooseberries (Ribes hirtellum), wild grapes (Vitis riparia), blackcurrants (Ribes nigrum), redcurrants (Ribes rubrum), haskap berries (Lonicera caerulea), wild raspberries (Rubus idaeus), wild blueberries (Vaccinium angustifolium), chokeberries (Aronia melanocarpa), buckthorn (Rhamnus cathartica), highbush cranberries (Viburnum trilobum), chokecherries (Prunus virginiana), nannyberries (Viburnum lentago) and snowberries (Symphoricarpos albus). The fatty acids, phytosterols, and terpenes were identified using Gas Chromatography-Mass Spectrometry (GC-MS). Lipid peroxidation and the antihypertensive activity assessed by measuring the berries' angiotensin converting enzyme 1 (ACE1) inhibitory activity were determined using in vitro methods. Notably, wild grapes exhibited the highest (p < 0.05) total fat content (7659 ± 312 μg per g DW), followed by haskap berries (4650 ± 184 μg per g DW). Polyunsaturated fatty acids (PUFAs) were highest (p < 0.05) in wild grapes (74%). Predominant phytosterols and terpenes identified in Canadian wild berries included β-sitosterol, isofucosterol, phytol, and α-amyrin. Saskatoon berries and gooseberries showed a distinct phytosterol and terpene profile compared to the other wild berries. Snowberries demonstrated the highest (p < 0.05) lipid peroxidation and the lowest (p < 0.05) angiotensin converting enzyme (ACE1) activity. This research provides valuable insights into the lipophilic bioactive compounds and their potential activities in vitro of the Canadian wild berries, offering a foundation for further exploration and potential applications in the context of nutraceuticals and functional foods.

Impact of Lactiplantibacillus plantarum and casein fortification on angiotensin converting enzyme inhibitory peptides in yogurt: identification and in silico analysis.

In this study, the effects of Lactiplantibacillus plantarum M11 (Lb. plantarum M11) in conjunction with sodium caseinate on the characteristics and angiotensin converting enzyme (ACE) inhibitory activity of yogurt were investigated. ACE inhibitory peptides (ACEIPs) in yogurt were identified by nano-LC-MS/MS and potential ACEIPs were predicted by in silico and molecular docking methods. The results showed that the ACE-inhibitory activity of yogurt was significantly enhanced (p < 0.05), while maintaining the quality characteristics of the yogurt. Thirteen ACEIPs in the improved yogurt (883 + M11-CS group) were identified, which were more abundant than the other yogurt groups (control 883 group, 883 + M11 group and 883-CS group). Two novel peptides with potential ACE inhibitory activity, YPFPGPIH and NILRFF, were screened. The two peptides showed PeptideRanker scores above 0.8, small molecular weight and strong hydrophobicity, and were non-toxic after prediction. Molecular docking results showed that binding energies with ACE were -9.4 kcal mol-1 and -10.7 kcal mol-1, respectively, and could bind to the active site of ACE. These results indicated that yogurt with Lb. plantarum M11 and sodium caseinate has the potential to be utilized as a functional food with antihypertensive properties. The combination of ACEIP-producing strains and casein fortification could be an effective method to promote the release of ACEIPs from yogurt.