BMY 7378, a selective α-adrenoceptor antagonist, is a new angiotensin converting enzyme inhibitor: In silico, in vitro and in vivo approach.

BMY 7378 is a multitarget drug primarily known for its selective antagonism of α-adrenoceptors (α-AR), exhibiting both hypotensive effects and the ability to prevent or reverse angiotensin II-induced vascular hypertrophy. Notably, BMY 7378 contains a phenylpiperazine moiety, a structural feature associated with angiotensin-converting enzyme (ACE) inhibition. This study aimed to investigate ACE inhibition as a potential pharmacological mechanism of BMY 7378.

Vasorelaxant and tracheorelaxant effects of Bocconia arborea and their isolated benzophenanthridine alkaloids.

Bocconia arborea S. Watson (Papaveraceae) is an abundant medicinal plant in the North of Morelos State, Mexico, which is used for the treatment of several diseases. The aim of current investigation was to isolate the compounds responsible of the relaxant effect shown by the active extracts.

Boroxazolidones: Synthesis, In Silico and In Vitro Evaluation as ACE/AChE Dual Inhibitors, and In Vivo Testing of Antihypertensive Activity.

Background: Systemic arterial hypertension is a serious chronic health problem caused by multiple factors. It is a major risk factor for Cardiovascular Diseases (CVDs), including heart failure, coronary heart disease, and myocardial infarction. Hypertension can be effectively treated with inhibitors of the Angiotensin Converting Enzyme (ACE), such as captopril, enalapril, and lisinopril.

LC-MS Fingerprinting Development for Standardized Precipitate from , Which Induces Antihypertensive Effect through NO Production and Calcium Channel Blockade.

The aim of this work was to evaluate the vasorelaxant and antihypertensive effects of a standardized precipitate of the hydroalcoholic extract from (PP), comprising ursolic acid, oleanolic acid, acacetin, luteolin and tilianin, among others. In the ex vivo experiments, preincubation with L-NAME (nonspecific inhibitor of nitric oxide synthases) reduced the relaxation induced by PP; nevertheless, preincubation with indomethacin (nonspecific inhibitor of cyclooxygenases) did not generate any change in the vasorelaxation, and an opposed effect was observed to the contraction generated by CaCl addition. Oral administration of 100 mg/kg of PP induced a significant acute decrease in diastolic (DBP) and systolic (SBP) blood pressure in spontaneously hypertensive rats, without changes in heart rate.

Ex Vivo and In Silico Approaches of Tracheal Relaxation through Calcium Channel Blockade of 6-Aminoflavone and Its Toxicological Studies in Murine Models.

Asthma is a condition in which a person's airways become inflamed, narrowed, and produce greater amounts of mucus than normal. It can cause shortness of breath, chest pain, coughing, or wheezing. In some cases, symptoms may be exacerbated.

Δ9-Tetrahydrocannabinol Treatment Modifies Insulin Secretion in Pancreatic Islets from Prediabetic Mice Under Hypercaloric Diet.

The endocannabinoid system over-activation is associated with type-2 diabetes mellitus onset, involving physiological, metabolic, and genetic alterations in pancreatic islets. The use of Δ9-Tetrahydrocannabinol (THC) as treatment is still controversial since its effects and mechanisms on insulin secretion are unclear. The aim of this study was to evaluate the effects of THC treatment in pancreatic islets from prediabetic mice.

Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of .

Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes.

High baseline expression of IL-6 and IL-10 decreased CCR7 B cells in individuals with previous SARS-CoV-2 infection during BNT162b2 vaccination.

The current pandemic generated by SARS-CoV-2 has led to mass vaccination with different biologics that have shown wide variations among human populations according to the origin and formulation of the vaccine. Studies evaluating the response in individuals with a natural infection before vaccination have been limited to antibody titer analysis and evaluating a few humoral and cellular response markers, showing a more rapid and intense humoral response than individuals without prior infection. However, the basis of these differences has not been explored in depth.

Antinociceptive and gastroprotective activities of Bocconia arborea S. Watson and its bioactive metabolite dihydrosanguinarine in murine models.

Ethnopharmacological Relevance: Bocconia arborea S. Watson (Papaveraceae) is known as "palo llora sangre" and is used in Mexican traditional medicine for the treatment of infections, it is also used as anxiolytic, analgesic, and antidiabetic, among others.

Aim Of The Study: to evaluate the antinociceptive and gastroprotective activities of extracts from B.

Angiotensin II Inhibits Insulin Receptor Signaling in Adipose Cells.

Angiotensin II (Ang II) is a critical regulator of insulin signaling in the cardiovascular system and metabolic tissues. However, in adipose cells, the regulatory role of Ang II on insulin actions remains to be elucidated. The effect of Ang II on insulin-induced insulin receptor (IR) phosphorylation, Akt activation, and glucose uptake was examined in 3T3-L1 adipocytes.

PPARα/γ, adiponectin, and GLUT4 overexpression induced by moronic acid methyl ester influenced glucose and triglyceride levels of experimental diabetic mice.

The current study aimed to determine the antidiabetic and antidyslipidemic activities of moronic acid methyl ester (1) (compound ) by in vivo, in vitro, in silico, and molecular biology studies. Compound was evaluated to establish its dose-dependent antidiabetic and antihyperglycemic (50 mg/kg) activities, in diabetic and normoglycemic male CD1 mice, respectively. Also, compound was subjected to a subacute study (50 mg/kg per day for 8 days) to determine blood biochemical profiles and the expression of protein tyrosine phosphatase 1B (), glucose transporter type 4 (), peroxisome proliferator-activated receptor α (), , adiponectin, interleukin-1β (IL-1β), and monocyte chemoattractant protein 1 (MCP-1) in adipose tissue of animals after treatment.

6-Amino-3-Methyl-4-(2-nitrophenyl)-1,4-Dihydropyrano[2,3-c]Pyrazole-5-Carbonitrile Shows Antihypertensive and Vasorelaxant Action via Calcium Channel Blockade.

Several 4-pyran derivatives were designed and synthesized previously as vasorelaxant agents for potential antihypertensive drugs. In this context, the objective of the present investigation was to determine the functional mechanism of vasorelaxant action of 6-amino-3-methyl-4-(2-nitrophenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (1: ) and its antihypertensive effect. Thus, compound 1: showed significant vasorelaxant action on isolated aorta rat rings pre-contracted with serotonin or noradrenaline, and the effect was not endothelium-dependent.

Antihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: In vivo, functional ex vivo and in silico studies.

Ethnopharmacological Relevance: Achillea millefolium L. (Asteraceae), known as yarrow (milenrama), is a plant used in Mexican traditional medicine for the treatment of hypertension, diabetes, and related diseases.

Aim: To determine the vasorelaxant and antihypertensive effect of A.

Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolites.

Ethnopharmacological Relevance: Tagetes lucida Cav. commonly known as "yauhtli" or "pericón" is used in Mexican traditional medicine for the treatment of anxiety, depressant diseases, pain, hypertension, among others.

Aim: To evaluate the antihypertensive and vasorelaxant modes of action of a crude ethanolic extract from T.

CARDIOMETABOLIC RISK FACTORS ASSOCIATED WITH RENAL FUNCTION IN APPARENTLY HEALTHY YOUNG STUDENTS: A CROSS-SECTIONAL STUDY.

Background: Cardiometabolic risk factors (CMRFs) appear decades before developing chronic kidney disease (CKD) in adulthood.

Objective: The objective of the study was to identify the prevalence and association between CMRFs and kidney function in apparently healthy young adults (18-25 years old).

Methods: We included 5531 freshman year students.

Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1.

The relationship of uric acid with macrophages has not been fully elucidated. We investigated the effect of uric acid on the proinflammatory ability of human macrophages and then examined the possible molecular mechanism involved. Primary human monocytes were differentiated into macrophages for subsequent exposure to 0, 0.

The α1D-adrenoreceptor antagonist BMY 7378 reverses cardiac hypertrophy in spontaneously hypertensive rats.

Objective: The α1D-adrenoreceptor (α1D-AR) is involved in angiotensin II-induced vascular remodeling and hypertension. Whether α1D-AR plays a role in hypertension-associated cardiac hypertrophy is unclear. Here we investigated effects of BMY 7378, a selective α1D-AR antagonist, on cardiac status in aged spontaneously hypertensive rats (SHR).

Novel CB1 receptor antagonist BAR-1 modifies pancreatic islet function and clinical parameters in prediabetic and diabetic mice.

Backgrouds: Cannabinoid receptor antagonists have been suggested as a novel treatment for obesity and diabetes. We have developed a synthetic cannabinoid receptor antagonist denominated BAR-1. As the function and integrity of a β-cell cellular structure are important keys for diabetes onset, we evaluated the effects of pharmacological administration of BAR-1 on prediabetic and diabetic rodents.

Potential role of angiotensin-(1-7) in the improvement of vascular insulin sensitivity after a bout of exercise.

New Findings: What is the central question of this study? What is the mechanism by which a bout of exercise increases subsequent insulin-stimulated vasodilatation? What is the main finding and its importance? Angiotensin-(1-7) through the Mas receptor participates in enhanced insulin-induced vasorelaxation after a bout of exercise in healthy rats. This new potential role of angiotensin-(1-7) could help in understanding how physical activity improves vascular insulin sensitivity in normal and insulin-resistant states.

Abstract: Exercise increases insulin-stimulated vasodilatation, but the mechanisms involved are unclear.

Aquaporin 8 is involved in H O -mediated differential regulation of metabolic signaling by α - and β-adrenoceptors in hepatocytes.

Reactive oxygen species participate in regulating intracellular signaling pathways. Herein, we investigated the reported opposite effects of hydrogen peroxide (H O ) on metabolic signaling mediated by activated α - and β-adrenoceptors (ARs) in hepatocytes. In isolated rat hepatocytes, stimulation of α -AR increases H O production via NADPH oxidase 2 (NOX2) activation.

Angiotensin-(1-7) Participates in Enhanced Skeletal Muscle Insulin Sensitivity After a Bout of Exercise.

A single bout of exercise increases subsequent insulin-stimulated glucose uptake in skeletal muscle; however, it is unknown whether angiotensin-(1-7) (Ang-(1-7)), a vasoactive peptide of the renin-angiotensin system, participates in this process. The aim of this study was to investigate the possible involvement of Ang-(1-7) in enhanced skeletal muscle insulin sensitivity after an exercise session. Male Wistar rats were forced to swim for 2.

Tracheal relaxation through calcium channel blockade of Achillea millefolium hexanic extract and its main bioactive compounds.

Ethnopharmacological Importance: Achillea millefolium L. (Asteraceae) is used for the treatment of respiratory diseases, diabetes, and hypertension.

Aim: to explore its tracheal relaxant properties and clarify its functional mechanism of action on smooth muscle cells, which allow us to propose it as a potential anti-asthmatic drug.

Antidiabetic effect of Cordia morelosana, chemical and pharmacological studies.

Ethnopharmacological Importance: CORDIA MORELOSANA: Standley (Boraginaceae) is commonly used in folk medicine for the treatment of diarrhoea, kidney inflammation, diabetes, lung pain, bronchitis, asthma, hoarseness, cough and fever.

Aim: Current work was conducted to develop a bio-guided isolation of antidiabetic compounds from ethanolic extract of Cordia morelosana (EECm).

Material And Methods: The phytochemical bio-guided study was conducted by successive chromatographic techniques, and isolated compounds were characterized by 1D and 2D-NMR experiments.

M2 macrophage immunotherapy abolishes glucose intolerance by increasing IL-10 expression and AKT activation.

Glucose intolerance associates with M1/M2 macrophage unbalance. We thus wanted to examine the effect of M2 macrophage administration on mouse model of glucose intolerance. C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks and then received thrice 20 mg/kg streptozotocin (HFD-GI).