scholarly journals Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Maurizio Forte ◽  
Valeria Conti ◽  
Antonio Damato ◽  
Mariateresa Ambrosio ◽  
Annibale A. Puca ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Vascular Diseases ◽  
Therapeutic Strategies ◽  
Vascular Homeostasis ◽  
The Family ◽  
No Signaling ◽  
Aggregation Control ◽  
Intercellular Messenger

Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases.

scholarly journals Inhibition of neuroinflammatory nitric oxide signaling suppresses glycation and prevents neuronal dysfunction in mouse prion disease

2021 ◽  
Vol 118 (10) ◽  
pp. e2009579118
Author(s):  
Julie-Myrtille Bourgognon ◽  
Jereme G. Spiers ◽  
Sue W. Robinson ◽  
Hannah Scheiblich ◽  
Paul Glynn ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Misfolding ◽  
Hippocampal Neurons ◽  
Therapeutic Potential ◽  
Early Disease ◽  
Nitric Oxide Signaling ◽  
Gene And Protein Expression ◽  
No Signaling ◽  
Nos Inhibitor

Several neurodegenerative diseases associated with protein misfolding (Alzheimer’s and Parkinson’s disease) exhibit oxidative and nitrergic stress following initiation of neuroinflammatory pathways. Associated nitric oxide (NO)-mediated posttranslational modifications impact upon protein functions that can exacerbate pathology. Nonenzymatic and irreversible glycation signaling has been implicated as an underlying pathway that promotes protein misfolding, but the direct interactions between both pathways are poorly understood. Here we investigated the therapeutic potential of pharmacologically suppressing neuroinflammatory NO signaling during early disease progression of prion-infected mice. Mice were injected daily with an NO synthase (NOS) inhibitor at early disease stages, hippocampal gene and protein expression levels of oxidative and nitrergic stress markers were analyzed, and electrophysiological characterization of pyramidal CA1 neurons was performed. Increased neuroinflammatory signaling was observed in mice between 6 and 10 wk postinoculation (w.p.i.) with scrapie prion protein. Their hippocampi were characterized by enhanced nitrergic stress associated with a decline in neuronal function by 9 w.p.i. Daily in vivo administration of the NOS inhibitor L-NAME between 6 and 9 w.p.i. at 20 mg/kg prevented the functional degeneration of hippocampal neurons in prion-diseased mice. We further found that this intervention in diseased mice reduced 3-nitrotyrosination of triose-phosphate isomerase, an enzyme involved in the formation of disease-associated glycation. Furthermore, L-NAME application led to a reduced expression of the receptor for advanced glycation end-products and the diminished accumulation of hippocampal prion misfolding. Our data suggest that suppressing neuroinflammatory NO signaling slows functional neurodegeneration and reduces nitrergic and glycation-associated cellular stress.

scholarly journals Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy

2011 ◽  
Vol 301 (3) ◽  
pp. H634-H646 ◽  
Author(s):  
Yixuan Zhang ◽  
Stefan P. Janssens ◽  
Kirstin Wingler ◽  
Harald H. H. W. Schmidt ◽  
An L. Moens
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Diseases ◽  
Endothelial Nitric Oxide Synthase ◽  
Therapeutic Strategy ◽  
No Synthase ◽  
Superoxide Formation ◽  
No Signaling ◽  
No Bioavailability ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The pathogenesis of many cardiovascular diseases is associated with reduced nitric oxide (NO) bioavailability and/or increased endothelial NO synthase (eNOS)-dependent superoxide formation. These findings support that restoring and conserving adequate NO signaling in the heart and blood vessels is a promising therapeutic intervention. In particular, modulating eNOS, e.g., through increasing the bioavailability of its substrate and cofactors, enhancing its transcription, and interfering with other modulators of eNOS pathway, such as netrin-1, has a high potential for effective treatments of cardiovascular diseases. This review provides an overview of the possibilities for modulating eNOS and how this may be translated to the clinic in addition to describing the genetic models used to study eNOS modulation.

scholarly journals Pin1 as Molecular Switch in Vascular Endothelium: Notes on Its Putative Role in Age-Associated Vascular Diseases

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3287
Author(s):  
Francesca Fagiani ◽  
Marieva Vlachou ◽  
Daniele Di Marino ◽  
Ilaria Canobbio ◽  
Alice Romagnoli ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelium ◽  
Vascular Diseases ◽  
The Elderly ◽  
No Production ◽  
Dependent Manner ◽  
Vascular Homeostasis ◽  
Apoptosis And Inflammation ◽  
Endothelial Nitric Oxide

By controlling the change of the backbones of several cellular substrates, the peptidyl-prolyl cis-trans isomerase Pin1 acts as key fine-tuner and amplifier of multiple signaling pathways, thereby inducing several biological consequences, both in physiological and pathological conditions. Data from the literature indicate a prominent role of Pin1 in the regulating of vascular homeostasis. In this review, we will critically dissect Pin1’s role as conformational switch regulating the homeostasis of vascular endothelium, by specifically modulating nitric oxide (NO) bioavailability. In this regard, Pin1 has been reported to directly control NO production by interacting with bovine endothelial nitric oxide synthase (eNOS) at Ser116-Pro117 (human equivalent is Ser114-Pro115) in a phosphorylation-dependent manner, regulating its catalytic activity, as well as by regulating other intracellular players, such as VEGF and TGF-β, thereby impinging upon NO release. Furthermore, since Pin1 has been found to act as a critical driver of vascular cell proliferation, apoptosis, and inflammation, with implication in many vascular diseases (e.g., diabetes, atherosclerosis, hypertension, and cardiac hypertrophy), evidence indicating that Pin1 may serve a pivotal role in vascular endothelium will be discussed. Understanding the role of Pin1 in vascular homeostasis is crucial in terms of finding a new possible therapeutic player and target in vascular pathologies, including those affecting the elderly (such as small and large vessel diseases and vascular dementia) or those promoting the full expression of neurodegenerative dementing diseases.

The molecular mechanism of mechanotransduction in vascular homeostasis and disease

2020 ◽  
Vol 134 (17) ◽  
pp. 2399-2418
Author(s):  
Yoshito Yamashiro ◽  
Hiromi Yanagisawa
Keyword(s):  
Shear Stress ◽  
Blood Vessels ◽  
Vessel Wall ◽  
Vascular Diseases ◽  
Cell Interactions ◽  
Aortic Aneurysms ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Vascular Homeostasis ◽  
Matrix Cell

Abstract Blood vessels are constantly exposed to mechanical stimuli such as shear stress due to flow and pulsatile stretch. The extracellular matrix maintains the structural integrity of the vessel wall and coordinates with a dynamic mechanical environment to provide cues to initiate intracellular signaling pathway(s), thereby changing cellular behaviors and functions. However, the precise role of matrix–cell interactions involved in mechanotransduction during vascular homeostasis and disease development remains to be fully determined. In this review, we introduce hemodynamics forces in blood vessels and the initial sensors of mechanical stimuli, including cell–cell junctional molecules, G-protein-coupled receptors (GPCRs), multiple ion channels, and a variety of small GTPases. We then highlight the molecular mechanotransduction events in the vessel wall triggered by laminar shear stress (LSS) and disturbed shear stress (DSS) on vascular endothelial cells (ECs), and cyclic stretch in ECs and vascular smooth muscle cells (SMCs)—both of which activate several key transcription factors. Finally, we provide a recent overview of matrix–cell interactions and mechanotransduction centered on fibronectin in ECs and thrombospondin-1 in SMCs. The results of this review suggest that abnormal mechanical cues or altered responses to mechanical stimuli in EC and SMCs serve as the molecular basis of vascular diseases such as atherosclerosis, hypertension and aortic aneurysms. Collecting evidence and advancing knowledge on the mechanotransduction in the vessel wall can lead to a new direction of therapeutic interventions for vascular diseases.

Current Advances in the Biological Activity of Polysaccharides in Dendrobium with Intriguing Therapeutic Potential

2018 ◽  
Vol 25 (14) ◽  
pp. 1663-1681 ◽  
Author(s):  
Chun-Ting Lee ◽  
Heng-Chun Kuo ◽  
Yung-Hsiang Chen ◽  
Ming-Yen Tsai
Keyword(s):  
Biological Activity ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Biological Effects ◽  
Herbal Medicines ◽  
Research Field ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
The Family ◽  
Anti Tumor Activity

The polysaccharides in many plants are attracting worldwide attention because of their biological activities and medical properties, such as anti-viral, anti-oxidative, antichronic inflammation, anti-hypertensive, immunomodulation, and neuron-protective effects, as well as anti-tumor activity. Denodrobium species, a genus of the family orchidaceae, have been used as herbal medicines for hundreds of years in China due to their pharmacological effects. These effects include nourishing the Yin, supplementing the stomach, increasing body fluids, and clearing heat. Recently, numerous researchers have investigated possible active compounds in Denodrobium species, such as lectins, phenanthrenes, alkaloids, trigonopol A, and polysaccharides. Unlike those of other plants, the biological effects of polysaccharides in Dendrobium are a novel research field. In this review, we focus on these novel findings to give readers an overall picture of the intriguing therapeutic potential of polysaccharides in Dendrobium, especially those of the four commonly-used Denodrobium species: D. huoshanense, D. offininale, D. nobile, and D. chrysotoxum.

Therapeutic Potential of Phosphodiesterase Inhibitors for Endothelial Dysfunction- Related Diseases

2020 ◽  
Vol 26 (30) ◽  
pp. 3633-3651 ◽  
Author(s):  
Javier Blanco-Rivero ◽  
Fabiano E. Xavier
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Phosphodiesterase Inhibitors ◽  
Developed Countries ◽  
Major Health Problem ◽  
Pde Inhibitors ◽  
Pharmaceutical Industries

Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3', 5'-monophosphate (cGMP) and adenosine 3', 5'-monophosphate (cAMP), also accompany many vascular disorders that course with altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide synthase expression and activation and to improve the morphological architecture of the endothelial surface. Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as an adjuvant in the pharmacotherapy of CVD.

An overview on therapeutic potential of Iris Persica

2020 ◽  
Vol 06 ◽  
Author(s):  
Faiq H. S. Hussain ◽  
Hawraz Ibrahim M. Amin ◽  
Dinesh kumar Patel ◽  
Omji Porwal
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Folk Medicine ◽  
Underground Storage ◽  
Kurdistan Region ◽  
Traditional Medicines ◽  
The Family ◽  
Storage Organs ◽  
Radical Generation ◽  
Perennial Herbs

: The family Iridaceae contains 92 genera and more than 1800 species, mostly perennial herbs with underground storage organs called rhizomes (bulbs). Some genera are important in traditional medicines, especially Iris and Gladiolus. The genus Iris belongs to this family and comprises about hundreds species among them, 12 species are found in Iraq. It has been widely used various medicines worldwide especially Iris persica is used in folk medicine in the Kurdistan region of Iraq as an effective treatment against tumours, antibacterial, antifungal and treating inflammation. Earlier finding confirmed that Iris persica and its constituents play role in the scavenging of free radical generation and prevention of disease pathogenesis. Each part of the Iris persica herb has some medicinal property. This review gives a eagle eye view mainly on the biological activities of the Iris persica and some of their compounds isolated, pharmacological actions of the Iris persica extracts and products, and plausible medicinal and therapeutically applications.

scholarly journals Effects of AGXT2 variants on blood pressure and blood sugar among 750 older Japanese subjects recruited by the complete enumeration survey method

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuta Yoshino ◽  
Hiroshi Kumon ◽  
Takaaki Mori ◽  
Taku Yoshida ◽  
Ayumi Tachibana ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Sugar ◽  
Vascular Diseases ◽  
Survey Method ◽  
Nucleotide Polymorphisms ◽  
Complete Enumeration ◽  
Plasma Adma ◽  
Oxide Synthase ◽  
Japanese Subjects

Abstract Background Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) is the only enzyme that degrades the R-form of 3-aminoisobutyrate, an intermediate metabolite of thymine. AGXT2, as well as diaminoarginine dimethylaminohydrolase 1 (DDAH1; EC 3.5.3.18), works as an enzyme that degrades asymmetric dimethylarginine (ADMA), which competitively inhibits the nitric oxide synthase family. Thus, these two enzyme activities may change vascular vulnerability for a lifetime via the nitric oxide (NO) system. We investigated the association between vascular conditions and diseases such as hypertension and diabetes mellitus and polymorphisms of these two genes in 750 older Japanese subjects (mean age ± standard deviation, 77.0 ± 7.6 years) recruited using the complete enumeration survey method in the Nakayama study. Demographic and biochemical data, such as blood pressure (BP) and casual blood sugar (CBS), were obtained. Four functional single nucleotide polymorphisms (SNPs; rs37370, rs37369, rs180749, and rs16899974) of AGXT2 and one functional insertion/deletion polymorphism in the promotor region with four SNPs (rs307894, rs669173, rs997251, and rs13373844) of DDAH1 were investigated. Plasma ADMA was also analyzed in 163 subjects. Results The results of multiple regression analysis showed that a loss of the functional haplotype of AGXT2, CAAA, was significantly positively correlated with BP (systolic BP, p = 0.034; diastolic BP, p = 0.025) and CBS (p = 0.021). No correlation was observed between DDAH1 and either BP or CBS. ADMA concentrations were significantly elevated in subjects with two CAAA haplotypes compared with subjects without the CAAA haplotype (p = 0.033). Conclusions Missense variants of AGXT2, but not DDAH1, may be related to vulnerability to vascular diseases such as hypertension and DM via the NO system.

scholarly journals Anti-Biofilm Molecules Targeting Functional Amyloids

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 795
Author(s):  
Leticia Matilla-Cuenca ◽  
Alejandro Toledo-Arana ◽  
Jaione Valle
Keyword(s):  
Biofilm Formation ◽  
Therapeutic Strategy ◽  
Research Area ◽  
Therapeutic Strategies ◽  
Structural Components ◽  
Significant Issue ◽  
Wide Range ◽  
Effective Therapeutic Strategy ◽  
Functional Amyloids ◽  
Biofilm Matrix

The choice of an effective therapeutic strategy in the treatment of biofilm-related infections is a significant issue. Amyloids, which have been historically related to human diseases, are now considered to be prevailing structural components of the biofilm matrix in a wide range of bacteria. This assumption creates the potential for an exciting research area, in which functional amyloids are considered to be attractive targets for drug development to dissemble biofilm structures. The present review describes the best-characterized bacterial functional amyloids and focuses on anti-biofilm agents that target intrinsic and facultative amyloids. This study provides a better understanding of the different modes of actions of the anti-amyloid molecules to inhibit biofilm formation. This information can be further exploited to improve the therapeutic strategies to combat biofilm-related infections.

scholarly journals Chalepin and Chalepensin: Occurrence, Biosynthesis and Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1609
Author(s):  
Lutfun Nahar ◽  
Shaymaa Al-Majmaie ◽  
Afaf Al-Groshi ◽  
Azhar Rasul ◽  
Satyajit D. Sarker
Keyword(s):  
Medicinal Plant ◽  
Critical Appraisal ◽  
Therapeutic Potential ◽  
Therapeutic Agents ◽  
Review Article ◽  
Natural Distribution ◽  
Antiplatelet Aggregation ◽  
Ruta Chalepensis ◽  
The Family ◽  
Novel Therapeutic

Dihydrofuranocoumarin, chalepin (1) and furanocoumarin, chalepensin (2) are 3-prenylated bioactive coumarins, first isolated from the well-known medicinal plant Ruta chalepensis L. (Fam: Rutaceae) but also distributed in various species of the genera Boenminghausenia, Clausena and Ruta. The distribution of these compounds appears to be restricted to the plants of the family Rutaceae. To date, there have been a considerable number of bioactivity studies performed on coumarins 1 and 2, which include their anticancer, antidiabetic, antifertility, antimicrobial, antiplatelet aggregation, antiprotozoal, antiviral and calcium antagonistic properties. This review article presents a critical appraisal of publications on bioactivity of these 3-prenylated coumarins in the light of their feasibility as novel therapeutic agents and investigate their natural distribution in the plant kingdom, as well as a plausible biosynthetic route.

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