Anxio-depressive phenotype and impaired memory in mice with a conditional knockout of brain-derived neurotrophic factor in endothelial cells.

The present study investigated the role of endothelial brain-derived neurotrophic factor (BDNF) in cognition. Male adult mice with a selective knockout of BDNF in endothelial cells () and their wild-type (WT) littermates were subjected to tests for detection of anxiety- and depression-like behaviors and impaired recognition memory. Neuronal activity and synaptogenesis were assessed from hippocampal levels of c-fos and synaptophysin, respectively, and cerebral capillary density from forebrain levels of CD31.

Discovery of New Highly Potent Histamine H Receptor Antagonists, Calcium Channel Blockers, and Acetylcholinesterase Inhibitors.

At present, one of the most promising strategies to tackle the complex challenges posed by Alzheimer's disease (AD) involves the development of novel multitarget-directed ligands (MTDLs). To this end, we designed and synthesized nine new MTDLs using a straightforward and cost-efficient one-pot Biginelli three-component reaction. Among these newly developed compounds, one particular small molecule, named has emerged as a promising MTDL.

Vasorelaxant and hypotensive effects of an ethanolic extract of and its main compound quercetin 3-methyl ether 3'-O-β-xylopyranoside.

plants were traditionally used to treat diseases associated with endothelial dysfunction. The present study investigated the effects of an ethanolic extract of Willd. (commonly named water lily, WL) and its main compound (quercetin 3-methyl ether 3'-O--xylopyranoside) on vascular function in rats.

A treadmill exercise reduced cardiac fibrosis, inflammation and vulnerability to ischemia-reperfusion in rat pristane-induced arthritis.

Aims: To explore cardiac structural and functional parameters and myocardial sensitivity to ischemia in a rat model of chronic arthritis, pristane-induced arthritis (PIA), and to investigate the effects of a running exercise protocol on cardiac disorders related to rheumatoid arthritis (RA).

Main Methods: 3 groups of male Dark Agouti rats were formed: Controls, PIA and PIA-Exercise. The PIA-Exercise group was subjected to an individualized treadmill running protocol during the remission phase.

A revisited version of the disputatio for pharmacological training: An educational study.

Objective: The disputatio is a pedagogical method existing since the Middle-Ages where students had to debate about a question asked by a "master", exercising their thinking and oratory skills. To move away from traditional vertical teaching methods, the disputatio has been revived by pharmacologists. Thus, for almost three successive years, several groups of young French pharmacologists and therapists confronted their ideas concerning a medical question at a therapeutic impasse.

Phosphodiesterase 5 and Arginase Inhibitory Activities of the Extracts from Some Members of Nelumbonaceae and Nymphaeaceae Families.

The objectives of this study were (1) to investigate the effect of extracts from some plants in the families Nelumbonaceae and Nymphaeaceae on phosphodiesterase 5 (PDE5) and arginase, which have been used in erectile dysfunction treatment, and (2) to isolate and identify the compounds responsible for such activities. The characterization and quantitative analysis of flavonoid constituents in the active extracts were performed by HPLC. Thirty-seven ethanolic extracts from different parts of plants in the genus and of Nymphaeaceae and genus of Nelumbonaceae were screened for PDE5 and arginase inhibitory activities.

The new quinazoline derivative (N-methyl-N-[(thiophen-2-yl)methyl]quinazoline-2,4-diamine) vasodilates isolated mesenteric arteries through endothelium-independent mechanisms and has acute hypotensive effects in Wistar rats.

During the screening of new N,N-disubstituted quinazoline 2,4-diamines as phosphodiesterase-5 inhibitors and pulmonary artery vasodilators, one N-methyl-N-[(thiophen-2-yl)methyl]quinazoline-2,4-diamine (compound 8) presented a greater selectivity for systemic than pulmonary vasculature. The present study aimed to characterize its vasorelaxant and hypotensive effects in Wistar rats. Vasorelaxant effects of compound 8 and underlying mechanisms were evaluated on isolated mesenteric arteries.

Relevance of circulating markers of endothelial activation for cardiovascular risk assessment in rheumatoid arthritis: a narrative review.

Rheumatoid arthritis (RA) is associated with excessive cardiovascular mortality secondary to premature atherosclerosis, in which endothelial activation (EA) plays a central role. EA is characterized by loss of vascular integrity, expression of leucocyte adhesion molecules, transition from antithrombotic to prothrombotic phenotype, cytokines production, shedding of membrane microparticles and recruitment of endothelial progenitor cells. As EA is an early event in atherogenesis, circulating markers of EA are putative markers of vascular pathology and cardiovascular (CV) risk.

Quinazoline-based human phosphodiesterase 5 inhibitors exhibited a selective vasorelaxant effect on rat isolated pulmonary arteries involving NO-sGC-cGMP pathway and calcium inhibitory effects.

Phosphodiesterase 5 (PDE5) inhibitors are an attractive option among the currently available therapies in the management of pulmonary arterial hypertension (PAH). Good selectivity for PDE5 is associated with reduced side effects and greater vasorelaxant effect on pulmonary arteries (PA). This study investigated the vasorelaxant effects of a series of quinazoline-based PDE5 inhibitors and their precise mechanisms action using rat isolated PA and aorta, as compared to sildenafil.

Effects of local cryotherapy on systemic endothelial activation, dysfunction, and vascular inflammation in adjuvant-induced arthritis (AIA) rats.

Aim: This study explored the systemic vascular effects of local cryotherapy with a focus on endothelial changes and arterial inflammation in the model of rat adjuvant-induced arthritis (AIA).

Methods: Cryotherapy was applied twice a day on hind paws of AIA rats from the onset of arthritis to the acute inflammatory phase. Endothelial activation was studied in the aorta by measuring the mRNA levels of chemokines (CXCL-1, MCP-1 (CCL-2), MIP-1α (CCL-3)) and adhesion molecules (ICAM-1, VCAM-1) by qRT-PCR.

Endothelial TrkB receptor activation controls vascular tone of rat middle cerebral artery.

Little is known on the cerebrovascular BDNF (brain-derived neurotrophic factor)/TrkB (tropomyosin related kinase B) pathway. This study investigated the contribution of endogenous endothelial BDNF to the control of vascular tone of rat middle cerebral artery (MCA) and the capacity of exogenous agonist of TrkB receptors to induce their relaxation. Endothelial cells constitutively expressed both BDNF and activated TrkB receptors.

Tofacitinib improved peripheral endothelial dysfunction and brain-derived neurotrophic factor levels in the rat adjuvant-induced arthritis model.

This study aimed to explore the effect of Tofacitinib on endothelial dysfunction and cerebral levels of brain-derived neurotrophic factor (BDNF) in the adjuvant-induced arthritis (AIA) rat model. Tofacitinib (10 mg/kg twice a day) or vehicle was administered from the first signs of inflammation. Arthritis scores were daily monitored while other parameters including endothelial function assessed from aortic rings, radiographic scores, blood pressure, heart rate, circulating levels of triglycerides, cholesterol, and interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-17A, and cerebral BDNF levels were determined after 3 weeks of treatment.

Intestinal permeability in spondyloarthritis and rheumatoid arthritis: A systematic review of the literature.

Objectives: To describe the current methods usable to assess intestinal permeability in spondyloarthritis (SpA) and rheumatoid arthritis (RA), to analyze the available data on intestinal permeability in SpA and RA patients and the effects of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) on intestinal permeability.

Methods: A systematic review was conducted. Medline, Embase, and Cochrane Library databases were searched.

Animal models to study pathogenesis and treatments of cardiac disorders in rheumatoid arthritis: Advances and challenges for clinical translation.

Although cardiac diseases such as acute myocardial infarction, heart failure and arrhythmias are the leading cause of cardiovascular complications in rheumatoid arthritis (RA), their pathogenesis is far from being understood and optimal therapeutic options to treat specifically these disorders in RA are lacking. Preclinical studies on animal models of arthritis can help to decipher the complex link between arthritis and the heart, and to identify critical pathways and novel therapeutic targets. This review presented the available data on cardiac disorders in animal models of RA, as well as the current knowledge on pathophysiology and pharmacology of these disorders.

Mammalian Arginase Inhibitory Activity of Methanolic Extracts and Isolated Compounds from Species.

Polyphenolic enriched extracts from two species of , and , possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (-), together with three other stilbenes, -resveratrol (), -scirpusin A (), -cyperusphenol A (), and two flavonoids, aureusidin () and luteolin (), which were isolated for the first time from and . Structures were established on the basis of the spectroscopic data from MS and NMR experiments.

A reconciling hypothesis centred on brain-derived neurotrophic factor to explain neuropsychiatric manifestations in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease characterized by synovitis leading to joint destruction, pain and disability. Despite efficient antirheumatic drugs, neuropsychiatric troubles including depression and cognitive dysfunction are common in RA but the underlying mechanisms are unclear. However, converging evidence strongly suggests that deficit in brain-derived neurotrophic factor (BDNF) signalling contributes to impaired cognition and depression.

Adjuvant-induced arthritis is a relevant model to mimic coronary and myocardial impairments in rheumatoid arthritis.

Objectives: To determine if the adjuvant-induced arthritis model reproduced coronary and cardiac impairments observed in rheumatoid arthritis patients. The link between disease activity and circulating levels of angiotensin II and endothelin-1 have been studied, as well as the myocardial susceptibility to ischemia.

Methods: At the acute inflammatory phase, coronary reactivity was assessed in isolated arteries, and cardiac function was studied in isolated perfused hearts, before and after global ischemia/reperfusion.

Impact of glucocorticoids on systemic sirtuin 1 expression and activity in rats with adjuvant-induced arthritis.

The class III histone deacetylase sirtuin 1 (SIRT1) plays a pivotal role in numerous biological and physiological functions, including inflammation. An association between SIRT1 and proinflammatory cytokines might exist. In addition to their important role in inflammation associated with rheumatoid arthritis (RA), proinflammatory cytokines mediate the development of systemic effects.

Arginase inhibitory properties of flavonoid compounds from the leaves of Mulberry (Morus alba, Moraceae).

Objectives: We aimed to isolate and identify bioactive molecules from Morus alba (Moraceae) leaves having arginase inhibitory activity towards the combat of clinical outcomes related to endothelial dysfunction.

Method: Extraction and isolation were carried out by successive macerations, prepurification by using a Solid Phase Extraction (SPE) and separation using preparative PLC. The structures of the isolated components were established and confirmed by spectroscopic analyses, including the ESI-HRMS and NMR spectroscopic investigations.

Vasorelaxant effects of Crataegus pentagyna: Links with arginase inhibition and phenolic profile.

Ethnopharmacological Relevance: Crataegus leaves, flowers and fruits have been traditionally used to improve blood circulation, numerous preclinical and clinical studies supporting the cardiovascular benefits of Crataegus preparations. In this respect, there is very limited data on Crataegus pentagyna; in addition, the chemical profile of this species is still incompletely elucidated.

Aim Of The Study: The objective of this study was to examine the cardiovascular benefits of Crataegus pentagyna Waldst.

New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition.

New tritarget small molecules combining Ca channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound has been identified as a very promising lead, showing good Ca channels blockade activity (IC = 21 ± 1 μM), potent affinity against hH3R ( = 565 ± 62 nM), a moderate but selective hBuChE inhibition (IC = 7.83 ± 0.

Metabolite profiling, arginase inhibition and vasorelaxant activity of Cornus mas, Sorbus aucuparia and Viburnum opulus fruit extracts.

The present study investigated the effects of Cornus mas, Sorbus aucuparia and Viburnum opulus fruit extracts on arginase activity and arterial vasodilation. V. opulus fruit extract exerted the highest vasorelaxant activity in phenylephrine precontracted rat aortic rings (EC = 6.

Vascular Arginase Is a Relevant Target to Improve Cerebrovascular Endothelial Dysfunction in Rheumatoid Arthritis: Evidence from the Model of Adjuvant-Induced Arthritis.

Emerging data revealed that rheumatoid arthritis (RA) is associated with higher risk of cerebrovascular diseases. Whereas cerebral endothelial dysfunction is acknowledged as a critical aspect of cerebrovascular diseases, its presence in RA and the mechanisms involved are currently unknown. By using the model of rat adjuvant-induced arthritis (AIA), the present study investigated cerebrovascular reactivity in pressurized middle cerebral arteries (MCA) on day 33 post-immunization.