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https://www.readbyqxmd.com/read/28798396/flavonoid-glycosides-isolated-from-epimedium-brevicornum-and-their-estrogen-biosynthesis-promoting-effects
#1
Fu Li, Bao-Wen Du, Dan-Feng Lu, Wen-Xuan Wu, Kanjana Wongkrajang, Lun Wang, Wen-Chen Pu, Chang-Lu Liu, Han-Wei Liu, Ming-Kui Wang, Fei Wang
Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1-4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28792962/aberrant-cgmp-signaling-persists-during-recovery-in-mice-with-oxygen-induced-pulmonary-hypertension
#2
Marta Perez, Keng Jin Lee, Herminio J Cardona, Joann M Taylor, Mary E Robbins, Gregory B Waypa, Sara K Berkelhamer, Kathryn N Farrow
Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine monophosphate (cGMP) signaling pathway has not been well studied in BPD-associated PH. In addition, there is little data about the natural history of hyperoxia-induced PH in mice or the utility of phosphodiesterase-5 (PDE5) inhibition in established disease...
2017: PloS One
https://www.readbyqxmd.com/read/28729555/inhibition-of-phosphodiesterase-5-suppresses-calcineurin-nfat-mediated-trpc6-expression-in-pulmonary-artery-smooth-muscle-cells
#3
Shaojun Li, Yilin Pan, Rui Ke, Xinming Xie, Cui Zhai, Wenhua Shi, Jian Wang, Xin Yan, Limin Chai, Qingting Wang, Qianqian Zhang, Xiaofan Su, Lan Yang, Li Gao, Manxiang Li
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705807/augmentation-of-cgmp-pkg-pathway-and-colonic-motility-by-hydrogen-sulfide
#4
Ancy D Nalli, Sayak Bhattacharya, Hongxia Wang, Derek M Kendig, John R Grider, Karnam S Murthy
Hydrogen sulfide (H2S), like nitric oxide (NO), causes smooth muscle relaxation, but unlike NO, does not stimulate soluble guanylyl cyclase (sGC) activity and generate cGMP. The aim of this study was to investigate the interplay between NO and H2S in colonic smooth muscle. In colonic smooth muscle from rabbit, mouse and human, L-cysteine, substrate of cystathionine-γ-lyase (CSE), or NaHS, an H2S donor, inhibited phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels, IP3 receptor phosphorylation at Ser(1756) (measured as a proxy for PKG activation), and muscle relaxation in response to NO donor, s-nitrosoglutathione (GSNO), suggesting augmentation of cGMP/PKG pathway by H2S...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28686445/discovery-and-optimization-of-chromeno-2-3-c-pyrrol-9-2h-ones-as-novel-selective-and-orally-bioavailable-phosphodiesterase-5-inhibitors-for-the-treatment-of-pulmonary-arterial-hypertension
#5
Deyan Wu, Tianhua Zhang, Yiping Chen, Yadan Huang, Haiju Geng, Yanfa Yu, Chen Zhang, Zengwei Lai, Yinuo Wu, Xiaolei Guo, Jianwen Chen, Hai-Bin Luo
Phosphodiesterase 5 (PDE5) inhibitors have been used as clinical agents to treat erectile dysfunction and pulmonary arterial hypertension (PAH). Herein, we detail the discovery of a novel series of chromeno[2,3-c]pyrrol-9(2H)-one derivatives as selective and orally bioavailable inhibitors against phosphodiesterase 5. Medicinal chemistry optimization resulted in 2, which exhibits a desirable inhibitory potency of 5.6 nM with remarkable selectivity as well as excellent pharmacokinetic properties and an oral bioavailability of 63...
July 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28677661/a-novel-therapeutic-approach-in-the-treatment-of-pulmonary-arterial-hypertension-allium-ursinum-liophylisate-alleviates-symptoms-comparably-to-sildenafil
#6
Mariann Bombicz, Daniel Priksz, Balazs Varga, Andrea Kurucz, Attila Kertész, Akos Takacs, Aniko Posa, Rita Kiss, Zoltan Szilvassy, Bela Juhasz
Right-sided heart failure-often caused by elevated pulmonary arterial pressure-is a chronic and progressive condition with particularly high mortality rates. Recent studies and our current findings suggest that components of Wild garlic (Allium ursinum, AU) may play a role in reducing blood pressure, inhibiting angiotensin-converting enzyme (ACE), as well as improving right ventricle function in rabbit models with heart failure. We hypothesize that AU may mitigate cardiovascular damage caused by pulmonary arterial hypertension (PAH) and has value in the supplementary treatment of the complications of the disease...
July 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28648945/phosphodiesterase-5-inhibition-as-a-therapeutic-target-for-ischemic-stroke-a-systematic-review-of-preclinical-studies
#7
Joakim N E Ölmestig, Ida R Marlet, Atticus H Hainsworth, Christina Kruuse
Phosphodiesterase 5 inhibitors (PDE5i), such as sildenafil (Viagra®) are widely used for erectile dysfunction and pulmonary hypertension. Preclinical studies suggest that PDE5i may improve functional outcome following ischemic stroke. In this systematic review we aimed to evaluate the effects of selective PDE5i in animal models of brain ischaemia. A systematic search in Medline, Embase, and The Cochrane Library was performed including studies in English assessing the effects of selective PDE5i. 32 publications were included describing outcome in 3646 animals...
June 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28603047/tadalafil-induces-antiproliferation-apoptosis-and-phosphodiesterase-type-5-downregulation-in-idiopathic-pulmonary-arterial-hypertension-in-vitro
#8
Aya Yamamura, Eri Fujitomi, Naoki Ohara, Kikuo Tsukamoto, Motohiko Sato, Hisao Yamamura
Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease of the pulmonary artery resulting from a currently unidentified etiology. IPAH is pathologically characterized as sustained vasoconstriction and vascular remodeling of the pulmonary artery. Vascular remodeling is mediated by enhanced proliferation and reduced apoptosis in pulmonary arterial smooth muscle cells (PASMCs). Based on its pathological mechanism, specific phosphodiesterase type 5 (PDE5) inhibitors have been used in the treatment of IPAH...
September 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28596298/sex-differences-in-pulmonary-vascular-control-focus-on-the-nitric-oxide-pathway
#9
Daphne P M de Wijs-Meijler, A H Jan Danser, Irwin K M Reiss, Dirk J Duncker, Daphne Merkus
Although the incidence of pulmonary hypertension is higher in females, the severity and prognosis of pulmonary vascular disease in both neonates and adults have been shown to be worse in male subjects. Studies of sex differences in pulmonary hypertension have mainly focused on the role of sex hormones. However, the contribution of sex differences in terms of vascular signaling pathways regulating pulmonary vascular function remains incompletely understood. Consequently, we investigated pulmonary vascular function of male and female swine in vivo, both at rest and during exercise, and in isolated small pulmonary arteries in vitro, with a particular focus on the NO-cGMP-PDE5 pathway...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28506928/distinct-phosphodiesterase-5a-containing-compartments-allow-selective-regulation-of-cgmp-dependent-signalling-in-human-arterial-smooth-muscle-cells
#10
Lindsay S Wilson, Manhong Guo, M Bibiana Umana, Donald H Maurice
Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO(·)) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca(2+) in human platelets...
May 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28469435/inhibition-of-phosphodiesterase-5-and-increasing-the-level-of-cyclic-guanosine-3-5-monophosphate-by-hydroalcoholic-achillea-wilhelmsii-c-koch-extract-in-human-breast-cancer-cell-lines-mcf-7-and-mda-mb-468
#11
Ramin Saravani, Hamid Reza Galavi, Ali Shahraki
This study aimed to investigate the effect of hydroalcoholic Achillea wilhelmsii C. Koch extract (HAWE) on phosphodiesterase 5 (PDE5) gene expression and cyclic guanosine 3',5' monophosphate (cGMP) signaling in the MCF-7 and MDA-Mb-468 cell lines. The effective dose (ED50) of HAWE was examined in both cell lines using a 3-(4,5-dimethylhiazol-2-yl)-2,5-diphenyltetrazolium bromide viability test, and the type of cell death was detected by flow cytometry. The expression of PDE5 and the concentration of cGMP were measured in a time-dependent manner in the ED50 by real-time polymerase chain reaction and a colorimetric assay, respectively...
2017: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/28414103/apoptosis-induction-of-poly-s-nitrosated-human-serum-albumin-in-resistant-solid-tumor-under-hypoxia-can-be-restored-by-phosphodiesterase-5-inhibition
#12
Mayumi Ikeda, Yu Ishima, Victor T G Chuang, Tsuyoshi Ikeda, Ryo Kinoshita, Hiroshi Watanabe, Tatsuhiro Ishida, Masaki Otagiri, Toru Maruyama
Poly-S-nitrosated human serum albumin (Poly-SNO-HSA) delivered and accumulated nitric oxide (NO) in tumors and induces apoptosis. Tumor hypoxia is strongly associated with malignant progression and tumor resistance to therapy. In this study, we examined the cytotoxic effect of Poly-SNO-HSA under hypoxia on the murine colon 26 adenocarcinoma (C26) cells in vitro and in vivo. Under hypoxia, at about 4 times LD50 dose of Poly-SNO-HSA in vitro, the reactive oxygen species production was hindered but apoptotic cells were induced via cGMP pathway as the effect was suppressed by a soluble guanylate cyclase inhibitor, NS2028...
April 13, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28398017/differential-effects-of-phosphodiesterase-5-inhibition-in-chronic-cardiac-decompensation-depending-on-the-type-whether-hfref-or-hfpef-of-heart-failure-a-meta-analysis
#13
Renato DE Vecchis, Arturo Cesaro, Carmelina Ariano
INTRODUCTION: According to 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension(PH), no specific drug is currently indicated for PH related to left heart disease( PH-LDH), i.e., the one secondary to left chronic heart failure (CHF), which coincides with the group 2 of the PH classification endorsed by the above-mentioned guidelines. In fact, adoption of therapies that specifically apply for so-called pulmonary arterial hypertension (group 1 of the PH classification) has been regarded as substantially contraindicated in patients with PH- LHD, according to current ESC/ERS guidelines...
April 10, 2017: Minerva Cardioangiologica
https://www.readbyqxmd.com/read/28337142/icariside-ii-effectively-reduces-spatial-learning-and-memory-impairments-in-alzheimer-s-disease-model-mice-targeting-beta-amyloid-production
#14
Lingli Yan, Yuanyuan Deng, Jianmei Gao, Yuangui Liu, Fei Li, Jingshan Shi, Qihai Gong
Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer's disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28316997/sildenafil-can-affect-innate-and-adaptive-immune-system-in-both-experimental-animals-and-patients
#15
REVIEW
Monika Kniotek, Agnieszka Boguska
Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28294194/phosphodiesterase-5-inhibition-preserves-renal-hemodynamics-and-function-in-mice-with-diabetic-kidney-disease-by-modulating-mir-22-and-bmp7
#16
Riccardo Pofi, Daniela Fiore, Rita De Gaetano, Giuseppe Panio, Daniele Gianfrilli, Carlotta Pozza, Federica Barbagallo, Yang Kevin Xiang, Konstantinos Giannakakis, Susanna Morano, Andrea Lenzi, Fabio Naro, Andrea M Isidori, Mary Anna Venneri
Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. Preclinical and experimental studies show that PDE5 inhibitors (PDE5is) exert protective effects in DN improving perivascular inflammation. Using a mouse model of diabetic kidney injury we investigated the protective proprieties of PDE5is on renal hemodynamics and the molecular mechanisms involved. PDE5i treatment prevented the development of DN-related hypertension (P < 0.001), the increase of urine albumin creatinine ratio (P < 0...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213937/targeting-phosphodiesterase-5-as-a-therapeutic-option-against-myocardial-ischemia-reperfusion-injury-and-in-treating-heart-failure
#17
REVIEW
Sevil Korkmaz-Icöz, Tamás Radovits, Gábor Szabó
Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cyclic 3´-5´guanosine monophosphate (cGMP) into 5'-GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP-dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil, and avanafil...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28155571/the-augmentation-of-bk-channel-activity-by-nitric-oxide-signaling-in-rat-cerebral-arteries-involves-co-localized-regulatory-elements
#18
Barry D Kyle, Ramesh C Mishra, Andrew P Braun
Large conductance, Ca(2+)-activated K(+) (BK) channels control cerebrovascular tone; however, the regulatory processes influencing these channels remain poorly understood. Here, we investigate the cellular mechanisms underlying the enhancement of BK current in rat cerebral arteries by nitric oxide (NO) signaling. In isolated cerebral myocytes, BK current magnitude was reversibly increased by sodium nitroprusside (SNP, 100 μM) and sensitive to the BK channel inhibitor, penitrem-A (100 nM). Fostriecin (30 nM), a protein phosphatase type 2A (PP2A) inhibitor, significantly prolonged the SNP-induced augmentation of BK current and a similar effect was produced by sildenafil (30 nM), a phosphodiesterase 5 (PDE5) inhibitor...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28124739/the-regulation-of-transient-receptor-potential-canonical-4-trpc4-channel-by-phosphodiesterase-5-inhibitor-via-the-cyclic-guanosine-3-5-monophosphate
#19
Jinhong Wie, SeungJoo Jeong, Misun Kwak, Jongyun Myeong, MeeRee Chae, Jong Kwan Park, Sung Won Lee, Insuk So
The transient receptor potential (TRP) protein superfamily consists of a diverse group of cation channels that bear structural similarities to the fruit fly Drosophila TRP. The TRP superfamily is distinct from other groups of ion channels in displaying a large diversity in ion selectivity, modes of activation, and physiological functions. Classical TRP (transient receptor potential canonical (TRPC)) channels are activated by stimulation of Gq-PLC-coupled receptors and modulated by phosphorylation. The cyclic guanosine monophosphate (cGMP)-PKG pathway is involved in the regulation of TRPC3 and TRPC6 channels...
January 26, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#20
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
February 21, 2017: Oncotarget
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