gw-6471 has been researched along with palmidrol* in 6 studies
6 other study(ies) available for gw-6471 and palmidrol
Article | Year |
---|---|
Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway.
Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA-PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and markedly reduced the production of TNF-α, IL-6, IL-1β, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor α (PPAR-α) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-α pathway. Topics: Amides; Amidohydrolases; Animals; Anti-Inflammatory Agents; beta Carotene; Cytokines; Enzyme Inhibitors; Ethanolamines; Inflammation; Lipopolysaccharides; Mice; Nitric Oxide; Oxazoles; Palmitic Acids; PPAR alpha; RAW 264.7 Cells; Tyrosine | 2020 |
Role of cannabinoid receptor 1 and the peroxisome proliferator-activated receptor α in mediating anti-nociceptive effects of synthetic cannabinoids and a cannabinoid-like compound.
Osteoarthritis (OA) is characterized by cartilage degeneration, subchondral sclerosis, and pain. Cannabinoids have well-established anti-nociceptive properties in animal models of chronic pain. The aim of this study is to evaluate the anti-nociceptive effects of synthetic cannabinoids (WIN-55,212 and HU210) and the cannabinoid-like compound palmitoylethanolamide (PEA) in rat models of OA and to assess the role of cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor α (PPARα) in mediating these effects. Intra-articular injection of monosodium iodoacetate (MIA) in the knee joint was used as a model of osteoarthritis. The von Frey filament test and weight-bearing difference were used to assess the anti-nociceptive effects of WIN-55,212, HU210, and PEA on MIA-induced OA in rats. Open-field locomotor activity system was used confirm the analgesic effects of those compounds. HU210, WIN55, 212, and PEA in a dose-dependent manner restored the paw withdrawal threshold (PWT) and the weight-bearing difference induced by MIA injection. SR141716A (a CB1 antagonist) significantly reversed the anti-nociceptive effects of all the administered drugs in terms of PWT. However, in terms of weight-bearing difference, SR141716A significantly reduced the anti-nociceptive effect of HU210 but not PEA or WIN55, 212. GW6471 (a PPARα antagonist) significantly reversed the anti-nociceptive effects of PEA but not those of HU210 or WIN55, 212. HU210, WIN55, 212 and PEA significantly restored the MIA-induced reduction in locomotor activity. In conclusions, both CB1 and PPARα receptors are involved in mediating pain in osteoarthritis. Therefore, targeting these receptors may be of great clinical value. Topics: Amides; Analgesics; Animals; Cannabinoids; Dronabinol; Ethanolamines; Iodoacetic Acid; Male; Motor Activity; Osteoarthritis; Oxazoles; Palmitic Acids; PPAR alpha; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Rimonabant; Tyrosine | 2019 |
The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice.
Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modulated by positive allosteric modulators (PAMs), ago-allosteric ligands (ago-PAMs), and α7-silent agonists. Activation of α7 nAChRs has been reported to increase the brain levels of endogenous ligands for nuclear peroxisome proliferator-activated receptors type-α (PPAR-α), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in a Ca Topics: alpha7 Nicotinic Acetylcholine Receptor; Amides; Animals; Azabicyclo Compounds; Benzamides; Bridged Bicyclo Compounds; Cannabinoid Receptor Antagonists; Ethanolamines; Furans; Male; Mice; Mice, Inbred ICR; Nicotinic Antagonists; Nociception; Oxazoles; Pain Measurement; Palmitic Acids; PPAR alpha; Receptor Cross-Talk; Signal Transduction; Tyrosine | 2017 |
Palmitoylethanolamide Regulates Production of Pro-Angiogenic Mediators in a Model of β Amyloid-Induced Astrogliosis In Vitro.
Topics: Adenosine Triphosphate; Amides; Amyloid beta-Peptides; Animals; Astrocytes; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Ethanolamines; Gliosis; Humans; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase Type II; Oxazoles; p38 Mitogen-Activated Protein Kinases; Palmitic Acids; Peptide Fragments; PPAR alpha; Rats; S100 Calcium Binding Protein beta Subunit; Tyrosine; Vascular Endothelial Growth Factor A | 2015 |
Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy.
N-palmitoylethanolamine (PEA), an endogenous fatty acid ethanolamide, plays a key role in the regulation of the inflammatory response and pain through, among others, activation of nuclear peroxisome proliferator-activated receptors (PPAR-α). Endogenous cannabinoids play a protective role in several central nervous system (CNS) disorders, particularly those associated with neuronal hyperexcitability. We investigated the effects of PEA and the role of PPAR-α in absence epilepsy using the WAG/Rij rat model. PEA, anandamide (AEA), a PPAR-α antagonist (GW6471) and a synthetic CB1 receptor antagonist/inverse agonist (SR141716) were administered to WAG/Rij rats in order to evaluate the effects on epileptic spike-wave discharges (SWDs) on EEG recordings. We studied also the effects of PEA co-administration with SR141716 and GW6471 and compared these effects with those of AEA to evaluate PEA mechanism of action and focusing on CB1 receptors and PPAR-α. Both PEA and AEA administration significantly decreased SWDs parameters (absence seizures). In contrast, GW6471 was devoid of effects while SR141716 had pro-absence effects. The co-administration of SR141716 with PEA or AEA completely blocked the anti-absence effects of these compounds. GW6471 antagonized PEA's effects whereas it did not modify AEA's effects. Furthermore, we have also measured PEA, AEA and 2-AG (2-arachidonoylglycerol) brain levels identifying significant differences between epileptic and control rats such as decreased PEA levels in both thalamus and cortex that might contribute to absence epilepsy. Our data demonstrate that PEA has anti-absence properties in the WAG/Rij rat model and that such properties depend on PPAR-α and indirect activation of CB1 receptors. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'. Topics: Amides; Animals; Anticonvulsants; Arachidonic Acids; Calcium Channel Blockers; Cannabinoid Receptor Antagonists; Dose-Response Relationship, Drug; Electroencephalography; Endocannabinoids; Epilepsy, Absence; Ethanolamines; Glycerides; Injections, Intraventricular; Lipid Metabolism; Male; Oxazoles; Palmitic Acids; Piperidines; Polyunsaturated Alkamides; PPAR alpha; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant; Tyrosine | 2013 |
Effects of palmitoylethanolamide on aqueous humor outflow.
To study the effects of palmitoylethanolamide (PEA), a fatty acid ethanolamide, on aqueous humor outflow facility.. The effects of PEA on outflow facility were measured using a porcine anterior segment-perfused organ culture model. The involvements of different receptors in PEA-induced changes were investigated using receptor antagonists and adenovirus delivered small hairpin RNAs (shRNAs). PEA-induced activation of p42/44 mitogen-activated protein kinase (MAPK) was determined by Western blot analysis using an antiphospho p42/44 MAPK antibody.. PEA caused a concentration-dependent enhancement of outflow facility, with the maximum effect (151.08 ± 11.12% of basal outflow facility) achieved at 30 nM of PEA. Pretreatment of anterior segments with 1 μM cannabinoid receptor 2 antagonist SR144528 and 1 μM PPARα antagonist GW6471, but not 1 μM cannabinoid receptor 1 antagonist SR141716A, produced a partial antagonism on the PEA-induced increase of outflow facility. Treatment of TM cells with PEA for 10 minutes activated phosphorylation of p42/44 MAPK, which was blocked by pretreatment with SR1444528 and GW6471, but not SR141716A. Knocking down the expression of either GPR55 or PPARα receptors with specific shRNAs for these receptors partially blocked PEA-induced increase in outflow facility and abolished PEA-induced phosphorylation of p42/44 MAPK. PD98059, an inhibitor of the p42/44 MAPK pathway, blocked both PEA-induced enhancement of aqueous humor outflow facility and PEA-induced phosphorylation of p42/44 MAPK.. Our results demonstrate that PEA increases aqueous humor outflow through the TM pathway and these effects are mediated by GPR55 and PPARα receptors through activation of p42/44 MAPK. Topics: Amides; Animals; Aqueous Humor; Blotting, Western; Camphanes; Dose-Response Relationship, Drug; Endocannabinoids; Enzyme Activation; Ethanolamines; Humans; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Organ Culture Techniques; Oxazoles; Palmitic Acids; Phosphorylation; Piperidines; PPAR alpha; Pyrazoles; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; Rimonabant; Swine; Trabecular Meshwork; Tyrosine | 2012 |