Abstract：
:Diabetic cardiomyopathy (DCM) is one of the major cardiac complications in diabetic patients and a major reason for the death of diabetic patients. Obeticholic acid (OCA) is a semi-synthetic bile acid analogue. The objective of the present study was to investigate the possible cardio-protective effect of OCA against DCM. db/db diabetic mice were given OCA with or without injection of LV-short hairpin farnesoid X receptor (shFXR), and general glucose and lipid metabolism, myocardial morphology and function, myocardial fibrosis, inflammation and oxidative stress were evaluated. We found that OCA significantly ameliorated metabolic dysfunctions. Moreover, OCA attenuated morphological injury of cardiac tissue, restored the abnormal changes of hemodynamic variables and echocardiographic parameters. The Sirius-Red staining of cardiac tissue and mRNA expression of fibrotic biomarkers, including connective tissue growth factor, osteopontin, Transforming growth factor-β1, atrial natriuretic peptide, Collagen Ⅰ, and Collagen Ⅲ were decreased by OCA. Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were reduced by OCA. Moreover, OCA decreased oxidant products and increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and the expression and activities of antioxidant enzymes. Injection of LV-shFXR downregulated FXR expression and inhibited all these beneficial effects of OCA. FXR is major target that mediated that beneficial effect of OCA. In summary, FXR/Nrf2 signaling was involved in OCA-induced amelioration of metabolic disorder, oxidative stress, inflammation, fibrosis and myocardial dysfunction. Our findings provide new evidence for the interaction of FXR and Nrf2 signaling and novel option for the intervention of DCM.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Wu H,Liu G,He Y,Da J,Xie Bdoi
10.1016/j.ejphar.2019.05.022subject
Has Abstractpub_date
2019-09-05 00:00:00pages
172393eissn
0014-2999issn
1879-0712pii
S0014-2999(19)30326-7journal_volume
858pub_type
杂志文章abstract：:The antiarrhythmic activity of amitriptyline, a tricyclic antidepressant, was evaluated in anesthetized dogs 24 h after coronary occlusion, during the period of spontaneous ventricular arrhythmias. In all experiments amitriptyline was administered i.v. in incremental doses of 0.3 mg/kg at 1 min intervals until a conve...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90404-1
更新日期：1978-10-01 00:00:00
abstract：:Guinea pig neurotensin differs from other mammalian neurotensin by the substitution of proline by serine at position 7. [Ser7]neurotensin produced a concentration-dependent contraction of the guinea pig oesophagus and rat fundus, a biphasic effect (initial relaxation followed by more sustained contraction) on the guin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90293-7
更新日期：1987-08-21 00:00:00
abstract：:In isolated rabbit aortae, imidazole (10(-4)M) caused a unique nonspecific potentiation of the contractile responses to prostaglandins, norepinephrine, 5-hydroxytryptamine, histamine and potassium only at low concentrations. Imidazole had no effect on the dose-response relationship for Ca2+ in the presence of potassiu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90255-2
更新日期：1982-09-24 00:00:00
abstract：:We have developed an isolated spinal cord-skin preparation of the newborn rat. The spinal cord together with a piece of skin connected to the cord by the saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were re...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90737-o
更新日期：1992-09-22 00:00:00
abstract：:An unbiased conditioned place preference paradigm was used to evaluate the effect of dextro-morphine on the morphine-produced reward in male CD rats. Morphine sulfate (1-10 mg/kg) given intraperitoneally dose-dependently produced the conditioned place preference. Pretreatment with dextro-morphine at a dose from 0.1 to...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.01.083
更新日期：2007-05-21 00:00:00
abstract：:The electrophysiological properties of the locus coeruleus (LC) neurons in response to acute and chronic administration of methylphenidate (MPD) were investigated. The extracellular LC neuronal activities were recorded from non-anesthetized, freely behaving rats previously implanted bilaterally with permanent semi mic...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.08.016
更新日期：2012-11-15 00:00:00
abstract：:Tracazolate (ICI 136,753) 4-butylamine-1-ethyl-6-methyl-1H-pyrazolo[3,4]pyridine-5-carboxylic acid ethyl ester is a non-benzodiazepine with anxiolytic-like activity in animal models. In contrast to the benzodiazepines, it enhances [3H]flunitrazepam binding in rat synaptic membrane fragments. The enhancement is potenti...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90033-4
更新日期：1982-03-12 00:00:00
abstract：:Lycopene, a natural carotenoid, has potential chemopreventive effects in many cancers. This study aimed to examine the effects of lycopene on regulating the inflammation and apoptosis of N-nitrosomethylbenzylamine(NMBzA) induced esophageal cancer in F344 rats. After the rats were fed normal diets containing different ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173230
更新日期：2020-08-15 00:00:00
abstract：:We discovered a novel compound, YM-126414 [1,3, 3-trimethyl-2-(2-phenylaminovinyl)-3H-indolium perchlorate], which stimulates glucose uptake in skeletal muscle cells in vitro. This compound increased the rate of consumption of glucose by C2C12 mouse myoblast cells in a dose-dependent manner (EC(50)=10 nM). To investig...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00880-3
更新日期：2000-12-20 00:00:00
abstract：:The uptake and release of 3H-dopamine was studied in slices of corpus striatum and substantia nigra in the presence of nialamide. High potassium triggered the outflow of tritium in both brain structures and this release was potentiated by GABA in a dose related fashion, whereas the spontaneous overflow of radioactivit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90127-4
更新日期：1979-01-15 00:00:00
abstract：:Taurine influx in the perfused rat heart was characterized and the effect of isoproterenol on this process determined. Hearts were perfused by the Langendorff technique with [3H]-taurine in a non-recirculating system. The rate of taurine influx was constant for at least 20 min and the process was saturable. A Km of 45...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90163-2
更新日期：1978-04-15 00:00:00
abstract：:Chemopreventive non-steroidal anti-inflammatory drugs (NSAIDs) exhibit diverse pharmacological and biological activities mainly through their inhibitory effect on cyclooxygenase (COX). However, COX-independent mechanisms involving kinase inhibition have been proposed to explain certain therapeutic effects of NSAIDs. H...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.04.012
更新日期：2010-07-25 00:00:00
abstract：:One of the recognized side effects of gentamicin is ototoxicity. The mechanism underlying the organ specificity of this side effect of gentamicin has not been fully established. In view of the fact that a number of pharmacologic agents are known to form complexes with melanin and melanin is an abundant constituent of ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)01793-4
更新日期：2002-06-20 00:00:00
abstract：:Aim of this study was to extend the knowledge on the antineoplastic effect of aloe-emodin (AE), a natural hydroxyanthraquinone compound, both in metastatic human melanoma cell lines and in primary stem-like cells (melanospheres). Treatment with AE caused reduction of cell proliferation and induction of SK-MEL-28 and A...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.05.057
更新日期：2015-09-05 00:00:00
abstract：:Hypoglycemia developed in fasted rats during forced swimming. This hypoglycemia was mostly abolished by phentolamine, an alpha-adrenolytic agent, or by hexamethonium; was potentiated by propranolol, a beta-adrenolytic agent, of by 5-methoxyindole-2-carboxylic acid, a gluconeogenic inhibitor; and was not affected by an...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90184-4
更新日期：1977-03-07 00:00:00
abstract：:We studied the effects of carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea) on the intracellular Ca(2+) concentration ([Ca(2+)](i)) in PC12 cells using fura-2 fluorescence imaging. Carmustine (100 microM) caused a delayed increase in [Ca(2+)](i) that developed within approximately 3 h. This effect was enhanced in cell...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.06.043
更新日期：2004-08-16 00:00:00
abstract：:We have previously demonstrated that the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has an antinociceptive effect on various pain stimuli in a naloxone-reversible manner. In the present study, the role of the endogenous opioid peptide β-endorphin in DHA-induced antinociception was examined. DHA-induced ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.05.047
更新日期：2011-09-01 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.08.013
更新日期：2017-11-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90385-h
更新日期：1992-02-18 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90056-n
更新日期：1993-03-23 00:00:00
abstract：:Perfusion of the 1S,3R isomer of trans-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 50 microM), or arachidonic acid (10 microM), for 5 min produced only depression of the field excitatory postsynaptic potential recorded in the CA1 region of rat hippocampal slices from which the CA3 region had been removed. However...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90919-9
更新日期：1993-08-24 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.11.047
更新日期：2004-02-06 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)81936-x
更新日期：1997-11-05 00:00:00
abstract：:We investigated the effects of 1-amino-5-bromouracil on the benzodiazepine-gamma-aminobutyric acid (GABA)A receptor complex to elucidate its central action. 1-Amino-5-bromouracil neither displaced nor enhanced [3H]muscimol, [35S]t-butylbicyclophosphorothionate (TBPS), or [3H]dehydroepiandrosterone sulfate binding to t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90278-x
更新日期：1994-12-12 00:00:00
abstract：:The antithrombotic effect of desethyl KBT-3022, which is the main active metabolite of the new antiplatelet agent, KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl] pyrrol-1-ylacetate; a cyclooxygenase inhibitor), was determined using a photochemically induced arterial thrombosis model in the rat femoral artery...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)83044-0
更新日期：1997-06-11 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90768-4
更新日期：1994-02-21 00:00:00
abstract：:GABAA receptors are pentameric chloride ion channels that are opened by GABA. We have screened a cell line derived from human glioblastoma, U3047MG, for expression of GABAA receptor subunit isoforms and formation of functional ion channels. We identified GABAA receptors subunit α2, α3, α5, β1, β2, β3, δ, γ3, π, and θ ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.12.001
更新日期：2015-02-05 00:00:00
abstract：:In the present study we investigated the in vivo pharmacological profile of the benz[e]indole cis-8-hydroxy-3-(n-propyl)],2,3a,4,5,9b-hexahydro-1H-benz[e]indole (cis-8-OH-PBZI), which has been described as a preferential dopamine D3 receptor agonist in vitro. The compound inhibited spontaneous locomotor activity in mi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01494-5
更新日期：1998-01-26 00:00:00
abstract：:Global forebrain ischemia results in damage to the pyramids in the CA1 hippocampal subfield, which is particularly vulnerable to excitotoxic processes. Morphological and functional disintegration of this area leads to a cognitive dysfunction and neuropsychiatric disorders. Treatment with N-methyl-d-aspartate receptor ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.05.069
更新日期：2011-09-30 00:00:00
abstract：:Adenosine monophosphate activated kinase (AMPK), a regulator of cellular metabolism, has been shown to relax arterial smooth muscle via endothelium-dependent and independent mechanisms. We have examined the role of AMPK in different smooth muscles using the activating compound, 5-amino-4-imidazolecarboxamide riboside-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.07.025
更新日期：2012-11-15 00:00:00
