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European Journal of Pharmacology

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https://www.readbyqxmd.com/read/29242120/osteoprotective-effects-of-salidroside-in-ovariectomized-mice-and-diabetic-mice
#1
Xiang-Fan Chen, Xiao-Li Li, Min Yang, Yan Song, Yan Zhang
Salidroside, an active constituent from the root of Rhodiola rosea L., has multiple pharmacological effects, such as anti-cancer, anti-inflammatory and anti-oxidative properties, etc. However, its protective effect on bone tissue via regulating calcium homeostasis is yet to be determined. This study was performed to investigate if salidroside could protect against bone injuries induced by estrogen deficiency or hyperglycemia through modulating calcium homeostasis. Ovariectomized (OVX) mice and diabetic mice were treated with salidroside (20mg/kg) for 6 weeks...
December 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29242119/pharmacological-modulation-of-ampa-receptor-phosphorylation-by-dopamine-and-muscarinic-receptor-agents-in-the-rat-medial-prefrontal-cortex
#2
Bing Xue, Li-Min Mao, Dao-Zhong Jin, John Q Wang
Two key transmitters in the medial prefrontal cortex (mPFC), dopamine and acetylcholine, are believed to interact with each other to modulate local glutamatergic transmission, although molecular mechanisms underlying their crosstalk are poorly understood. Here we investigated effects of pharmacological manipulations of dopamine and muscarinic receptors on phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult rat mPFC in vivo. We found that an agonist selective for Gαs-coupled dopamine D1 receptors, SKF81297, increased AMPA receptor GluA1 subunit phosphorylation at a protein kinase A-sensitive site (S845), while SKF81297 had no effect on GluA1 phosphorylation at S831...
December 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29242118/activation-of-transglutaminase-2-by-nerve-growth-factor-in-differentiating-neuroblastoma-cells-a-role-in-cell-survival-and-neurite-outgrowth
#3
Alanood S Algarni, Alan J Hargreaves, John M Dickenson
NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy...
December 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29237540/prokinetic-effects-of-neurokinin-2-receptor-agonists-on-the-bladder-and-rectum-of-rats-with-acute-spinal-cord-transection
#4
Lesley Marson, Karl B Thor, Mary Katofiasc, Edward C Burgard, Nadia M J Rupniak
The suitability of various neurokinin-2 (NK2) receptor agonists and routes of administration to elicit on-demand voiding of the bladder and bowel, as future therapy for individuals with spinal cord injury, was examined using a rat model. The current study examined the feasibility of alternative routes of administration, which are more practical for clinical use than intravenous (IV) administration. Voiding and isovolumetric cystometry were recorded in anesthetized, acutely spinalized, female rats after IV, subcutaneous (SC), intramuscular (IM), intranasal (IN), or sublingual (SL) administration of [Lys5,MeLeu9,Nle10]-NKA(4-10] (LMN-NKA)...
December 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29233661/hypoglycemic-mechanism-of-a-novel-proteoglycan-extracted-from-ganoderma-lucidum-in-hepatocytes
#5
Zhou Yang, Congheng Chen, Juan Zhao, Weijie Xu, Yanming He, Hongjie Yang, Ping Zhou
Protein tyrosine phosphatase 1 B (PTP1B) is one of main causes involved in type 2 diabetes, it dephosphorylates insulin receptor substrate (IRS) and dysregulates insulin signaling pathway, thus inducing insulin resistance. Our previous work first reported that FYGL, a neutral hyperbranched proteoglycan ingredient extracted from Ganoderma lucidum, has hypoglycemic activity in vivo and inhibitory potency on PTP1B in vitro, but the underlying mechanism was still unclear. In this study, we sought to investigate effects of FYGL on insulin signaling pathway involved with PTP1B as the targeting point in hepatocytes...
December 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29233660/negative-inotropic-effects-of-diadenosine-tetraphosphate-are-mediated-by-protein-kinase-c-and-phosphodiesterases-stimulation-in-the-rat-heart
#6
Nikolai Pakhomov, Ksenia Pustovit, Victoria Potekhina, Tatiana Filatova, Vladislav Kuzmin, Denis Abramochkin
Extracellular diadenosine polyphosphates (ApnA) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular ApnA cause alteration of the heart functioning via purine receptors in different mammalian species. Nevertheless, principal intracellular pathways which underlie ApnA action in the heart remain unknown. In the present study the role of the P2Y-associated intracellular regulatory pathway in the mediation of diadenosine tetraphosphate (Ap4A) effects in the rat heart has been investigated for the first time...
December 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29233659/klotho-upregulation-contributes-to-the-neuroprotection-of-ligustilide-against-cerebral-ischemic-injury-in-mice
#7
Fang-Yi Long, Men-Qi Shi, Hong-Jing Zhou, Dong-Ling Liu, Na Sang, Jun-Rong Du
Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a neuroprotective factor. Our previous studies showed that ligustilide minimizes the cognitive dysfunction and brain damage induced by cerebral ischemia; however, the underlying mechanisms remain unclear. This study aims to investigate whether klotho is involved in the protective effects of ligustilide against cerebral ischemic injury in mice. Cerebral ischemia was induced by bilateral common carotid arterial occlusion. Neurobehavioral tests as well as Nissl and Fluoro-Jade B staining were used to evaluate the protective effects of ligustilide in cerebral ischemia, and Western blotting and ELISA approaches were used to investigate the underlying mechanisms...
December 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29229534/a-novel-compound-dt-010-protects-against-doxorubicin-induced-cardiotoxicity-in-zebrafish-and-h9c2-cells-by-inhibiting-reactive-oxygen-species-mediated-apoptotic-and-autophagic-pathways
#8
Fan Tang, Xinhua Zhou, Liang Wang, Luchen Shan, Chuwen Li, Hefeng Zhou, Simon Ming-Yuen Lee, Maggie Pui-Man Hoi
Doxorubicin (Dox) is an effective anti-cancer agent but limited by its cardiotoxicity, thus the search for pharmacological agents for enhancing anti-cancer activities and protecting against cardiotoxicity has been a subject of great interest. We have previously reported the synergistic anti-cancer effects of a novel compound DT-010. In the present study, we further investigated the cardioprotective effects of DT-010 in zebrafish embryos in vivo and the molecular underlying mechanisms in H9c2 cardiomyocytes in vitro...
December 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29229533/xanthoceraside-attenuates-amyloid-%C3%AE-peptide1-42-induced-memory-impairments-by-reducing-neuroinflammatory-responses-in-mice
#9
Yue Qi, Xue-Fei Ji, Tian-Yan Chi, Peng Liu, Ge Jin, Qian Xu, Qing Jiao, Li-Hua Wang, Li-Bo Zou
Xanthoceraside, a novel triterpenoid saponin extracted from the husks of Xanthoceras sorbifolia Bunge, has neuroprotective effects in vivo and anti-inflammatory properties in vitro. However, the exact mechanism of xanthoceraside on anti-amyloid beta (Aβ)-induced neuroinflammatory responses has not been elucidated. Therefore, we used intracerebroventricular injection of amyloid 1-42 (Aβ1-42) to establish a mouse model to test the effects of xanthoceraside on Aβ-induced cognitive impairments and the TLR2/NF-κB and MAPK pathways...
December 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29229532/inflammation-and-renal-fibrosis-recent-developments-on-key-signaling-molecules-as-potential-therapeutic-targets
#10
REVIEW
Wenshan Lv, George W Booz, Yangang Wang, Fan Fan, Richard J Roman
Chronic kidney disease (CKD) is a major public health issue. At the histological level, renal fibrosis is the final common pathway of progressive kidney disease irrespective of the initial injury. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Some of the inflammatory signaling molecules involved in CKD include: monocyte chemoattractant protein-1 (MCP-1), bradykinin B1 receptor (B1R), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNFα), transforming growth factor β (TGF-β), and platelet-derived growth factor (PDGF)...
December 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29229531/eriodictyol-stimulates-insulin-secretion-through-camp-pka-signaling-pathway-in-mice-islets
#11
Abdul Hameed, Rahman M Hafizur, Nusrat Hussain, Sayed Ali Raza, Mujeeb-Ur-Rehman, Sajda Ashraf, Zaheer Ul-Haq, Faisal Khan, Ghulam Abbas, M Iqbal Choudhary
Eriodictyol, a flavonoid isolated from Lyonia ovalifolia, was found to be the most potent insulin secretagogue in our preliminary studies. Here, we explored mechanism(s) of insulin secretory activity of eriodictyol in vitro and in vivo. Mice islets and MIN6 cells were incubated in basal and stimulatory glucose containing eriodictyol with or without agonist/antagonist. Secreted insulin and cAMP contents were measured using ELISA kits. K+- and Ca2+-channels currents were recorded with patch-clamp technique. Oral glucose tolerance test and plasma insulin was evaluated in non-diabetic and diabetic rats...
December 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225193/synthesis-and-in-vitro-characterization-of-a-p2%C3%A3-7-radioligand-123i-tz6019-and-its-response-to-neuroinflammatory-in-a-mouse-model-of-alzheimer-disease
#12
Hongjun Jin, Junbin Han, Derek Resing, Hui Liu, Xuyi Yue, Rebecca L Miller, Kathleen M Schoch, Timothy M Miller, Joel S Perlmutter, Terrance M Egan, Zhude Tu
The purinergic receptor P2X ligand-gated ion channel 7 (P2×7 receptor) is a promising imaging target to detect neuroinflammation. Herein, we report development of a potent iodinated labeled radiotracer for P2×7 receptor, [123I]TZ6019. The radiosynthesis of [123I]TZ6019 was accomplished by allylic-tin precursor iodination using [123I]NaI with good radiochemical yield of 85% and high radiochemical purity of > 99%. Human embryonic kidney 293 (HEK-293) cell line stably transfected with the human P2×7 receptor was used to characterize the binding affinity of TZ6019 in fluorescence, radioactive competitive, and saturation binding assays...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225192/effects-of-the-new-psychoactive-substances-diclofensine-diphenidine-and-methoxphenidine-on-monoaminergic-systems
#13
Dino Luethi, Marius C Hoener, Matthias E Liechti
Diclofensine, diphenidine, and methoxphenidine are new psychoactive substances (NPSs) that recently appeared on the illicit drug market. Pharmacological profiling of such newly emerged drugs is crucial for a better understanding of their psychotropic effects and toxicity. We therefore investigated the potential of these NPSs to inhibit the norepinephrine, dopamine, and serotonin transporters in human embryonic kidney cells stably transfected with the respective transporters. In addition, we determined monoamine transporter and receptor affinities for the substances...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225191/the-comprehensive-electrophysiological-study-of-curcuminoids-on-delayed-rectifier-k-currents-in-insulin-secreting-cells
#14
Ping-Chung Kuo, Chia-Jung Yang, Yu-Chi Lee, Pei-Chun Chen, Yen-Chin Liu, Sheng-Nan Wu
Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic β-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents inherently in insulin-secreting cells remains largely unclear. The effects of CUR and other structurally similar curcuminoids on ion currents in rat insulin-secreting (INS-1) insulinoma cells were therefore investigated in this study. The effects of these compounds on ionic currents and membrane potential were studied by patch-clamp technique...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225190/scopolamine-induced-passive-avoidance-memory-retrieval-deficit-is-accompanied-with-hippocampal-mmp2-mmp-9-and-mapks-alteration
#15
Maryam Moosavi, Roksana SoukhakLari, Leila Moezi, Fatema Pirsalami
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and cognitive deficit. The observed amnesia in the early stages of AD is suggested to be a retrieval problem, rather than encoding and consolidation deficit. According to the cholinergic hypothesis of AD, scopolamine is used to induce an animal model of amnesia. Howbeit the effect of scopolamine on memory retrieval is contradictory. This study aimed to assess the effect of scopolamine on passive avoidance memory retrieval...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225189/luteolin-attenuates-airway-inflammation-by-inducing-the-transition-of-cd4-cd25-to-cd4-cd25-regulatory-t-cells
#16
Seung-Hyung Kim, Evelyn Saba, Bok-Kyu Kim, Won-Kyung Yang, Yang-Chun Park, Han Jae Shin, Chang Kyun Han, Young Cheol Lee, Man Hee Rhee
Regulatory T cells (Th2) play an important role in autoimmunity and have been shown to exert anti-inflammatory effects in allergic asthma. Mouse model of airway inflammation was used to examine the suppressive activity of luteolin-induced CD4+CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various biological processes were examined, including airway eosinophilia; mucus hypersecretion; elevation of OVA-specific IgE, expression of Th2 cytokines and chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper responsiveness (AHR)...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225188/rosuvastatin-improves-myocardial-hypertrophy-after-hemodynamic-pressure-overload-via-regulating-the-crosstalk-of-nrf2-are-and-tgf-%C3%AE-smads-pathways-in-rat-heart
#17
Pengbo Wang, Lin Luo, Qiusheng Shen, Gaoyong Shi, Anaz Mohammed, Songshi Ni, Xiang Wu
Left ventricular hypertrophy is more commonly associated with hemodynamic overload imposed by hypertension or volume overload. Transforming growth factor β (TGF-β) is involved in the cardiac hypertrophy and fibrosis of the left ventricle. The fact that TGF-β1 and the nuclear factor erythroid 2-related factor 2 (Nrf2) both become up-regulated upon persistent vessel overload suggests that these two factors may virtually impact on their signaling pathways. In this research, 40 rats were divided into sham group, model group, rosuvastatin low and high dose group...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225187/prostaglandin-d2-generation-from-human-lung-mast-cells-is-catalysed-exclusively-by-cyclooxygenase-1
#18
Bandar K Baothman, Jennifer Smith, Linda J Kay, S Kim Suvarna, Peter T Peachell
Mast cells are an exceptionally rich source of prostaglandin D2 (PGD2). PGD2 is pro-inflammatory and can cause bronchoconstriction. The enzyme cyclooxygenase (COX) is central to the generation of prostanoids such as PGD2. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX. COX exists as two isoforms, COX-1 and COX-2. The principal aim of this study was to establish whether COX-1 and/or COX-2 mediates PGD2 generation from human lung mast cells. Mast cells were isolated from human lung tissue and purified by flotation over Percoll and immunomagnetic bead separations...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225186/hinokitiol-inhibits-compound-action-potentials-in-the-frog-sciatic-nerve
#19
Nobuya Magori, Tsugumi Fujita, Eiichi Kumamoto
Hinokitiol (β-thujaplicin) is a natural tropolone derivative contained in Chamaecyparis taiwanensis that has various actions including anti-inflammatory activities. Various plant-derived compounds inhibit compound action potentials (CAPs) in a manner dependent on the chemical structure of the compounds; however, the effects of hinokitiol on nerve conduction have not been examined. To determine whether hinokitiol inhibits CAPs and, if so, the chemical structure of hinokitiol that is important in this inhibition, we examined the effects of hinokitiol and its related compounds on fast-conducting CAPs using the frog sciatic nerve and the air-gap method...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29223348/distinctive-binding-properties-of-the-negative-allosteric-modulator-3h-sb269-652-at-recombinant-dopamine-d3-receptors
#20
Irene Fasciani, Ilaria Pietrantoni, Mario Rossi, Clotilde Mannoury la Cour, Gabriella Aloisi, Francesco Marampon, Marco Scarselli, Mark J Millan, Roberto Maggio
Recently, employing radioligand displacement and functional coupling studies, we demonstrated that SB269,652 (N-[(1r,4r)-4-[2-(7-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide) interacts in an atypical manner with dopamine D3 receptor displaying a unique profile reminiscent of a negative allosteric ligand. Here, we characterized the binding of radiolabelled [3H]SB269,652 to human dopamine D3 receptor stably expressed in Chinese Hamster Ovary cells. Under saturating conditions, SB269,652 showed a KD value of ≈ 1nM...
December 6, 2017: European Journal of Pharmacology
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