Abstract：
BACKGROUND AND PURPOSE:Dehydrodiconiferyl alcohol (DHCA), a lignan compound isolated from Cucurbita moschata, has previously been shown to contain anti-adipogenic and antilipogenic effects on 3T3-L1 cells and mouse embryonic fibroblasts. As some of phytochemicals derived from natural plants show anti-inflammatory or antioxidative activities, we determined whether DHCA affects the production of pro-inflammatory mediators and also investigated its underlying mechanisms. EXPERIMENTAL APPROACH:Raw264.7, a murine macrophage cell line, and primary murine macrophages derived from bone marrow cells were treated with LPS in the presence of DHCA. Furthermore, cells were treated with LPS and palmitate in the presence of DHCA to examine its effect on inflammasomes. The production of various pro-inflammatory mediators was examined and the underlying mechanisms investigated using a variety of molecular biological techniques. To test whether DHCA exhibits anti-inflammatory effects in vivo, mouse dextran sodium sulfate (DSS)-induced colitis model was used. KEY RESULTS:DHCA reduced the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β and CCL2) and mediators (iNOS, COX-2 and ROS) by down-regulating the activity of I-κB kinase and, subsequently, the DNA binding activity of NF-κB. Moreover, DHCA effectively suppressed the palmitate-mediated activation of inflammasomes, which resulted in decreased production of IL-1β. DHCA also showed therapeutic effects in the mouse DSS-induced colitis model by suppressing the production of TNF-α and IL-1β and thus preventing weight loss and colon shrinkage. CONCLUSIONS AND IMPLICATIONS:Our data suggest that DHCA is a novel phytochemical that by regulating key molecules involved in inflammation and oxidative stress might exert a broad range of anti-inflammatory activities.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Lee J,Choi J,Kim Sdoi
10.1111/bph.13137subject
Has Abstractpub_date
2015-07-01 00:00:00pages
3353-69issue
13eissn
0007-1188issn
1476-5381journal_volume
172pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:Dexpramipexole, a drug recently tested in patients with amyotrophic lateral sclerosis (ALS,) is able to bind F1Fo ATP synthase and increase mitochondrial ATP production. Here, we have investigated its effects on experimental ischaemic brain injury. EXPERIMENTAL APPROACH:The effects of dexpramipe...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13790
更新日期：2018-01-01 00:00:00
abstract：:1. In decerebrated, non-spinalized rabbits, intrathecal administration of either of the selective 5-HT1A-receptor antagonists (S)WAY-100135 or WAY-100635 resulted in dose-dependent enhancement of the reflex responses of gastrocnemius motoneurones evoked by electrical stimulation of all myelinated afferents of the sura...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb16019.x
更新日期：1996-11-01 00:00:00
abstract：:1. Desensitization of the myocardial beta-adrenergic signal transduction pathway is an important mechanism which is involved in the progression of hypertensive heart disease. The aim of the present study was to evaluate the differential effects of chronic pharmacotherapy with an angiotensin converting enzyme (ACE)-inh...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701615
更新日期：1998-02-01 00:00:00
abstract：:1. The efflux and influx of tryptophan across the synaptosomal plasma membrane has been studied under a variety of experimental conditions, in order to examine the mechanism by which depolarization enhances the efflux of tryptophan from superfused synaptosomes. 2. Efflux of [3H]-tryptophan from preloaded superfused sy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11440.x
更新日期：1988-02-01 00:00:00
abstract：:1 Sera of rabbits immunized against a nocotinic receptor-rich fraction, obtained from the electric organ of Torpedo marmorata, were tested for their pharmacological activity on different in vitro preparations. 2 Sera containing antibodies against the nicotinic receptor blocked neuromuscular transmission in the phrenic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07651.x
更新日期：1976-05-01 00:00:00
abstract：:Using a rat model which allows serial blood sampling and concurrent brain microdialysis sampling, we have investigated the temporal kinetic inter-relationship of levetiracetam in serum and brain extracellular fluid (frontal cortex and hippocampus) following systemic administration of levetiracetam, a new antiepileptic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704141
更新日期：2001-07-01 00:00:00
abstract：:The pharmacological properties of endothelin receptors (ETR) were investigated in guinea-pig bronchus by comparing binding and functional results. In binding assays, both the ET(B) agonists, endothelin-3 (ET-3) and N-suc-[Glu9,Ala11,15]ET-1(8-21) (IRL 1620), and the antagonist, N-cis-2,6-dimethylpiperidinocarbonyl-L-g...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702672
更新日期：1999-07-01 00:00:00
abstract：:NO is a neurotransmitter released from enteric inhibitory neurons and responsible for modulating gastrointestinal (GI) motor behaviour. Enteric neurons express nNOS (NOS1) that associates with membranes of nerve varicosities. NO released from neurons binds to soluble guanylate cyclase in post-junctional cells to gener...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14459
更新日期：2019-01-01 00:00:00
abstract：:1. The serine/threonine protein phosphatase (PP) inhibitors, okadaic acid and calyculin, attenuated the IgE-mediated release of histamine from human lung mast cells (HLMC) and basophils in a dose-dependent manner whereas an alternative PP inhibitor, microcystin, was ineffective. Calyculin was more potent than okadaic ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702169
更新日期：1998-11-01 00:00:00
abstract：:The release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) from the strips of guinea-pig ileum was investigated in the presence of neurotensin. Neurotensin evoked the release of [3H]-GABA from the strips preloaded with [3H]-GABA, and the evoked release was Ca2+-dependent and tetrodotoxin-sensitive. Hexameth...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11204.x
更新日期：1987-03-01 00:00:00
abstract：:1. In order to define the electrophysiological mechanism(s) responsible for bradykinin (BK)-induced positive inotropic and chronotropic responses in isolated guinea-pig atria, effects of BK on the membrane currents were examined in isolated atrial cells using patch clamp techniques. 2. BK (0.1-1000 nM) increased the L...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702060
更新日期：1998-09-01 00:00:00
abstract：:1 The relationship of agonist efficacy to the rate of G protein-coupled receptor signaling desensitization is controversial. 2 Expressing inwardly rectifying potassium channels (GIRKs) in Xenopus oocytes, we have devised a signaling assay that clearly identifies CB1 cannabinoid receptor agonists with low intrinsic eff...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705792
更新日期：2004-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Benzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro. EXPERIMENTAL APPROACH:We assessed the effects of the benzofurans 5-APB, 5-APDB, 6-APB, 6-APDB, 4-APB, 7-APB, 5-EAPB and ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13128
更新日期：2015-07-01 00:00:00
abstract：:1. This study describes the effects of hypoxia on relaxing responses and cAMP production induced by the known vasodilator peptides: alphaCGRP, amylin (AMY) and adrenomedullin (AM) on isolated pig coronary arteries in vitro. 2. Hypoxic incubation increased the vasorelaxant effect of alphaCGRP (four-fold; P<0.05), AMY (...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706232
更新日期：2005-07-01 00:00:00
abstract：:1 Palmitaldehyde, olealdehyde and linolealdehyde acetal phosphatidic acids induced rapid shape change and dose-dependent biphasic aggregation of human platelets in platelet-rich plasma; aggregation was reversible at low doses and irreversible at high doses of the acetal phosphatidic acids. The palmitaldehyde congener ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10508.x
更新日期：1983-05-01 00:00:00
abstract：:1. Prostaglandin F2 alpha (PGF2 alpha) and its synthetic analogue, fluprostenol, potently relaxed the precontracted isolated jugular vein of the rabbit (RJuV). The vasorelaxant activity of PGF2 alpha and fluprostenol was dependent upon an intact vascular endothelium. Although removal of the vascular endothelium abolis...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15960.x
更新日期：1995-12-01 00:00:00
abstract：:1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4 rece...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705929
更新日期：2004-11-01 00:00:00
abstract：:1 The response of pentobarbitone-anaesthetized cats to the intravenous administration of E. coli endotoxin (2 mg/kg) consisted of acute pulmonary vasoconstriction (3-5 min after the injection) and a secondary shock phase characterized by delayed systemic hypotension, decreased central venous pressure and cardiac outpu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb08559.x
更新日期：1974-02-01 00:00:00
abstract：:1 The specific stimulating action of dopamine and L-DOPA on exocrine pancreatic secretion was further investigated in the isolated blood-perfused canine pancreas.2 6-Hydroxydopamine (100 mug, i.a.) stimulated the secretion but was far less potent than dopamine. Epinine (0.3-1 mg. i.a.), alpha-methyldopamine (10-300 mu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb09651.x
更新日期：1974-06-01 00:00:00
abstract：:1. Various neurotransmitters in the brain regulate gastric acid secretion. Previously, we reported that the central injection of kappa-opioid receptor agonists stimulated this secretion in rats. Although the existence of kappa(1)-kappa(3)-opioid receptor subtypes has been proposed, the character is not defined. We inv...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705082
更新日期：2003-03-01 00:00:00
abstract：:1. The ability of the neuroprotective agent, lifarizine (RS-87476), to mitigate veratridine-, cyanide- and glutamate-induced toxicity in rat embryonic cerebrocortical neurones in primary culture has been compared with that of tetrodotoxin (TTX), nitrendipine, (+)-MK-801 and (-)-MK-801. Lactate dehydrogenase (LDH) rele...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13357.x
更新日期：1995-04-01 00:00:00
abstract：:1. Different 5-hydroxytryptamine (5-HT) receptor subtypes mediate different behavioural responses. Compounds acting at more than one 5-HT receptor exert behavioural effects which may be the result of response competition or a specific interaction between pathways within the CNS. Therefore the mutual interaction betwee...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14138.x
更新日期：1990-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Protocatechuic acid (PCA) is plentiful in edible fruits and vegetables and is thus one anti-oxidative component of normal human diets. However, the molecular mechanisms involved in the chemopreventive activity of PCA are poorly understood. Here, we investigated the mechanism(s) underlying the ant...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01022.x
更新日期：2011-01-01 00:00:00
abstract：:1. Turning behaviour after unilateral lesions of the nigro-striatal dopamine pathway in rats has been used to compare the actions of cocaine and desipramine on central dopamine-containing neurones.2. Administration of cocaine alone (5-20 mg/kg) resulted in no turning or minimal turning towards the lesioned side; the m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08156.x
更新日期：1973-01-01 00:00:00
abstract：:Data presentation and statistical analysis in scientific writing are agreed to be in need of improvement, despite the profusion of advice and instruction. Recent evidence supports the need for better planning and analysis of animal experiments. This series of short articles aims to provide advice in small easily diges...
journal_title：British journal of pharmacology
pub_type： 社论
doi：10.1111/j.1476-5381.2011.01251.x
更新日期：2011-05-01 00:00:00
abstract：:1. In the present work, we have studied the expression of Fos during acute and chronic administration of the kappa-opioid receptor agonist U-50488H and after U-5088H withdrawal in the rat hypothalamic paraventricular nucleus (PVN). Fos production was also studied in brainstem regions that innervate the PVN: the A(2) c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705179
更新日期：2003-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5-HT by monoamine oxidase (MAO), as well as the hepati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01453.x
更新日期：2012-02-01 00:00:00
abstract：:1. Prolongation of action potentials by cooling or pharmacological treatment can restore conduction in demyelinated axons. We have assessed the ability of pyrethroids (in vitro) to modify action potential kinetics and to reverse conduction block in lesioned peripheral nerve. 2. Fast Na+ currents were isolated in mamma...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701644
更新日期：1998-02-01 00:00:00
abstract：:1 The question whether constriction of local vessels is essential for the anti-inflammatory action of glucocorticoids in carrageenin-induced granulomatous inflammation was studied. 2 The vasodilator prostaglandin E1 injection into the granuloma pouch fluid increased the exudation of plasma protein into the granuloma t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb16794.x
更新日期：1981-07-01 00:00:00
abstract：:The sensitivity of the uterus to the inhibition of contractions by salbutamol, diltiazem or nifedipine was assessed in the ovariectomized, post-partum rat by dose-response curves following bolus intravenous (i.v.) administration. These tests were performed before (day 1), immediately after a 20 h i.v. infusion of salb...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10238.x
更新日期：1986-07-01 00:00:00
