511 results match your criteria N-palmitoylethanolamine


Anti-Inflammatory, Antioxidant and Crystallographic Studies of N-Palmitoyl-ethanol Amine (PEA) Derivatives.

Molecules 2017 Apr 11;22(4). Epub 2017 Apr 11.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, Arcavacata di Rende (CS) 87036, Italy.

-Palmitoyl-ethanolamine (PEA) is an anti-inflammatory component of egg yolk that is usually employed for the prevention of respiratory apparatus virus infection and then frequently used for its efficient anti-inflammatory and analgesic effects in experimental models of visceral, neuropathic, and inflammatory diseases. Nevertheless, data of its use in animal or human therapy are still scarce and further studies are needed. Herein, we report the biological evaluation of a small library of -palmitoyl-ethanolamine analogues or derivatives, characterized by a protected acid function (either as palmitoyl amides or hexadecyl esters), useful to decrease their hydrolysis rate in vitro and prolong their biological activity. Read More

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http://dx.doi.org/10.3390/molecules22040616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154659PMC
April 2017
8 Reads

Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor.

Sci Rep 2017 03 23;7(1):375. Epub 2017 Mar 23.

Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Università degli Studi della Campania "Luigi Vanvitelli" (Ex SUN), 80138, Naples, Italy.

The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. Read More

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http://dx.doi.org/10.1038/s41598-017-00342-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428303PMC

Ultra-micronized Palmitoylethanolamide: An Efficacious Adjuvant Therapy for Parkinson's Disease.

CNS Neurol Disord Drug Targets 2017 ;16(6):705-713

Department of Neurology, Movement Disorder Center, San Giuseppe Hospital, Empoli, Florence. Italy.

Background: Parkinson's disease (PD) is the subject of intense efforts to develop strategies that slow down or stop disease progression and disability. Substantial evidence points to a prominent role for neuroinflammation in the underlying dopaminergic cell death. Ultramicronized palmitoylethanolamide (um-PEA) is well-known for its ability to promote the resolution of neuroinflammation and exert neuroprotection. Read More

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http://dx.doi.org/10.2174/1871527316666170321124949DOI Listing
May 2018
1 Read

Use of palmitoylethanolamide in carpal tunnel syndrome: a prospective randomized study.

J Orthop Traumatol 2017 Dec 15;18(4):451-455. Epub 2017 Mar 15.

Hospital Sant Rafael, Pg. Vall d'Hebron 107-117, 08035, Barcelona, Catalonia, Spain.

Background: Palmitoylethanolamide (PEA) is an endogenous fatty acid amide that has shown anti-inflammatory activity and neuroprotection and has been used for the treatment of compressive syndromes. The aim of this study is to investigate the clinical and electrophysiological effects of conservative treatment with PEA in low to moderate carpal tunnel syndrome (CTS).

Materials And Methods: A prospective double-blinded randomized study was performed on 61 patients with a clinical and electrophysiologically confirmed diagnosis of low and moderate CTS. Read More

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http://dx.doi.org/10.1007/s10195-017-0453-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685977PMC
December 2017
4 Reads

Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.

Aliment Pharmacol Ther 2017 04 6;45(7):909-922. Epub 2017 Feb 6.

Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy.

Background: Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. Read More

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http://doi.wiley.com/10.1111/apt.13958
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http://dx.doi.org/10.1111/apt.13958DOI Listing
April 2017
1 Read

Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion.

Lipids Health Dis 2017 Jan 19;16(1):14. Epub 2017 Jan 19.

Department of Biomedical Sciences, Cittadella Universitaria di Monserrato, 09042, Monserrato, CA, Italy.

Background: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma. Read More

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http://dx.doi.org/10.1186/s12944-016-0389-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5248520PMC
January 2017
56 Reads
2.220 Impact Factor

N-Palmitoylethanolamine-Oxazoline as a New Therapeutic Strategy to Control Neuroinflammation: Neuroprotective Effects in Experimental Models of Spinal Cord and Brain Injury.

J Neurotrauma 2017 09 24;34(18):2609-2623. Epub 2017 Aug 24.

1 Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina , Messina, Italy .

Modulation of N-acylethanolamine-hydrolyzing acid amidase (NAAA) represents a potential alternative strategy in the treatment of neuroinflammation. Recent studies showed that pharmacological modulation of NAAA could be achieved with the oxazoline of palmitoylethanolamide (PEA; PEA-OXA). The aim of this study was to evaluate the neuroprotective effects of PEA-OXA in the secondary neuroinflammatory events induced by spinal and brain trauma in mice. Read More

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http://dx.doi.org/10.1089/neu.2016.4808DOI Listing
September 2017
10 Reads

N-acylethanolamine-hydrolyzing acid amidase and fatty acid amide hydrolase inhibition differentially affect N-acylethanolamine levels and macrophage activation.

Biochim Biophys Acta Mol Cell Biol Lipids 2017 May 6;1862(5):474-484. Epub 2017 Jan 6.

Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Bruxelles, Belgium. Electronic address:

N-acylethanolamines (NAEs) such as N-palmitoylethanolamine and anandamide are endogenous bioactive lipids having numerous functions, including the control of inflammation. Their levels and therefore actions can be controlled by modulating the activity of two hydrolytic enzymes, N-acylethanolamine-hydrolyzing acid amidase (NAAA) and fatty acid amide hydrolase (FAAH). As macrophages are key to inflammatory processes, we used lipopolysaccharide-activated J774 macrophages, as well as primary mouse alveolar macrophages, to study the effect of FAAH and NAAA inhibition, using PF-3845 and AM9053 respectively, on macrophage activation and NAE levels measured by HPLC-MS. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13881981173000
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http://dx.doi.org/10.1016/j.bbalip.2017.01.001DOI Listing
May 2017
15 Reads

Plasma palmitoylethanolamide (PEA) as a potential biomarker for impaired coronary function.

Int J Cardiol 2017 Mar 13;231:1-5. Epub 2016 Dec 13.

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; IRCCS AOU San Martino-IST, Genova, largo Benzi 10, 16143 Genoa, Italy; Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 viale Benedetto XV, 16132 Genoa, Italy.. Electronic address:

Background: Among endocannabinoid (EC)-related mediators, Oleoyl-ethanolamide (OEA) and Palmitoyl-ethanolamide (PEA), two endogenous PPARα agonists with lipolytic and anti-inflammatory action, respectively, are being actively investigated. Here, we assessed the potential association between plasma levels of PEA and OEA and coronary function in a cohort including normal, overweight, obese, and morbidly obese (MOB) individuals.

Methods: Myocardial perfusion and endothelium-related myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with N-ammonia positron emission tomography/computed tomography. Read More

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http://dx.doi.org/10.1016/j.ijcard.2016.12.023DOI Listing
March 2017
6 Reads

Efficacy of Body Lotion Containing N-palmitoylethanolamine in Subjects with Chronic Pruritus due to Dry Skin: A Dermatocosmetic Study.

Acta Derm Venereol 2017 05;97(5):639-641

Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Von-Esmarch-Str. 58, DE-48149Münster, Germany.

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http://dx.doi.org/10.2340/00015555-2593DOI Listing
May 2017
5 Reads

Palmitoylethanolamide reduces inflammation and itch in a mouse model of contact allergic dermatitis.

Eur J Pharmacol 2016 Nov 5;791:669-674. Epub 2016 Oct 5.

Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy; Endocannabinoid Research Group, Italy.

In mice, 2,4-dinitrofluorobenzene (DNFB) induces contact allergic dermatitis (CAD), which, in a late phase, is characterized by mast cell (MC) infiltration and angiogenesis. Palmitoylethanolamide (PEA), an endogenous anti-inflammatory molecule, acts by down-modulating MCs following activation of the cannabinoid CB receptor and peroxisome proliferator-activated receptor-α (PPAR-α). We have previously reported the anti-inflammatory effect of PEA in the early stage of CAD. Read More

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http://dx.doi.org/10.1016/j.ejphar.2016.10.005DOI Listing
November 2016
9 Reads

Pharmacokinetic-pharmacodynamic influence of N-palmitoylethanolamine, arachidonyl-2'-chloroethylamide and WIN 55,212-2 on the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

Eur J Pharmacol 2016 Nov 20;791:523-534. Epub 2016 Sep 20.

Science of Health Department, Clinical Pharmacology Unit, School of Medicine, University "Magna Graecia" of Catanzaro, Italy. Electronic address:

We evaluated the effects of ACEA (selective cannabinoid (CB) receptor agonist), WIN 55,212-2 mesylate (WIN; non-selective CB and CB receptor agonist) and N-palmitoylethanolamine (PEA; an endogenous fatty acid of ethanolamide) in DBA/2 mice, a genetic model of reflex audiogenic epilepsy. PEA, ACEA or WIN intraperitoneal (i.p. Read More

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http://dx.doi.org/10.1016/j.ejphar.2016.09.029DOI Listing
November 2016
18 Reads

Calcium-dependent generation of N-acylethanolamines and lysophosphatidic acids by glycerophosphodiesterase GDE7.

Biochim Biophys Acta 2016 12 13;1861(12 Pt A):1881-1892. Epub 2016 Sep 13.

Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan. Electronic address:

N-Acylethanolamines form a class of lipid mediators and include an endocannabinoid arachidonoylethanolamide (anandamide), analgesic and anti-inflammatory palmitoylethanolamide, and appetite-suppressing oleoylethanolamide. In animal tissues, N-acylethanolamines are synthesized from N-acylated ethanolamine phospholipids directly by N-acylphosphatidylethanolamine-hydrolyzing phospholipase D or through multi-step pathways via N-acylethanolamine lysophospholipids. We previously reported that glycerophosphodiesterase (GDE) 4, a member of the GDE family, has lysophospholipase D (lysoPLD) activity hydrolyzing N-acylethanolamine lysophospholipids to N-acylethanolamines. Read More

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http://dx.doi.org/10.1016/j.bbalip.2016.09.008DOI Listing
December 2016
71 Reads

Palmitoylethanolamide protects mice against 6-OHDA-induced neurotoxicity and endoplasmic reticulum stress: In vivo and in vitro evidence.

Pharmacol Res 2016 11 8;113(Pt A):276-289. Epub 2016 Sep 8.

Department of Pharmacy, University of Naples "Federico II", 80131, Naples, Italy.

Several pathogenetic factors have been involved in the onset and progression of Parkinson's disease (PD), including inflammation, oxidative stress, unfolded protein accumulation, and apoptosis. Palmitoylethanolamide (PEA), an endogenous N-acylethanolamine, has been shown to be a neuroprotective and anti-inflammatory molecule, acting as a peroxisome proliferator activated receptor (PPAR)-α agonist. In this study we investigated the effects of PEA on behavioral alterations and the underlying pathogenic mechanisms in the 6-hydroxydopamine (6-OHDA)-induced model of PD in male mice. Read More

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http://dx.doi.org/10.1016/j.phrs.2016.09.004DOI Listing
November 2016
17 Reads

Palmitoylethanolamide Reverses Paclitaxel-Induced Allodynia in Mice.

J Pharmacol Exp Ther 2016 Nov 8;359(2):310-318. Epub 2016 Sep 8.

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (G.D.; J.L.W.; M.I.D.; A.H.L.); and Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy (G.D.).

Chemotherapy-induced peripheral neuropathy (CIPN) represents a serious complication associated with antineoplastic drugs. Although there are no medications available that effectively prevent CIPN, many classes of drugs have been used to treat this condition, including anticonvulsants, serotonin and noradrenaline reuptake inhibitors, and opioids. However, these therapeutic options yielded inconclusive results in CIPN clinical trials and produced assorted side effects with their prolonged use. Read More

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http://dx.doi.org/10.1124/jpet.116.236182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074488PMC
November 2016
5 Reads

Beneficial Effects of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism.

CNS Neurosci Ther 2017 Jan 4;23(1):87-98. Epub 2016 Oct 4.

Department of Chemical, Biological, Pharmacological and Environmental Sciences, University of Messina, Messina, Italy.

Aims: Autism spectrum disorder (ASD) is a condition defined by social communication deficits and repetitive restrictive behaviors. Association of the fatty acid amide palmitoylethanolamide (PEA) with the flavonoid luteolin displays neuroprotective and antiinflammatory actions in different models of central nervous system pathologies. We hypothesized that association of PEA with luteolin might have therapeutic utility in ASD, and we employed a well-recognized autism animal model, namely sodium valproate administration, to evaluate cognitive and motor deficits. Read More

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http://dx.doi.org/10.1111/cns.12648DOI Listing
January 2017
5 Reads

N-palmitoylethanolamide in the anterior cingulate cortex attenuates inflammatory pain behaviour indirectly via a CB1 receptor-mediated mechanism.

Pain 2016 12;157(12):2687-2696

aPharmacology and Therapeutics, National University of Ireland, Galway, Ireland bGalway Neuroscience Centre and Centre for Pain Research, National University of Ireland, University Road, Galway, Ireland cPhysiology, School of Medicine, National University of Ireland, Galway, Ireland.

The neural substrates and mechanisms mediating the antinociceptive effects of the endogenous bioactive lipid, N-palmitoylethanolamide (PEA), require further investigation. We investigated the effects of exogenous PEA administration into the anterior cingulate cortex (ACC), an important brain region linked with cognitive and affective modulation of pain, on formalin-evoked nociceptive behaviour in rats. Potential involvement of peroxisome proliferator-activated receptor isoforms (PPAR) α and γ or endocannabinoid-mediated entourage effects at cannabinoid1 (CB1) receptors or transient receptor potential subfamily V member 1 (TRPV1) in mediating the effects of PEA was also investigated. Read More

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http://dx.doi.org/10.1097/j.pain.0000000000000687DOI Listing
December 2016

Adelmidrol, a Palmitoylethanolamide Analogue, as a New Pharmacological Treatment for the Management of Inflammatory Bowel Disease.

Mol Pharmacol 2016 Nov 13;90(5):549-561. Epub 2016 Sep 13.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy (M.C., D.I., E.G., R.S., R.C., E.E.,S.C.); and Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri (S.C.)

Leukocyte infiltration, improved levels of intercellular adhesion molecule 1 (ICAM-1), and oxidative stress in the colon are the principal factors in inflammatory bowel disease. The goal of the current study was to explore the effects of adelmidrol, an analog of the anti-inflammatory fatty acid amide signaling molecule palmitoylethanolamide, in mice subjected to experimental colitis. Additionally, to clarify whether the protective action of adelmidrol is dependent on the activation of peroxisome proliferator-activated receptors (PPARs), we investigated the effects of a PPARγ antagonist, GW9662, on adelmidrol action. Read More

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http://dx.doi.org/10.1124/mol.116.105668DOI Listing
November 2016
8 Reads

Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα.

FASEB J 2017 02 13;31(2):469-481. Epub 2016 Sep 13.

School of Medicine, Royal Derby Hospital, University of Nottingham, Nottingham, United Kingdom;

Cannabinoids modulate intestinal permeability through cannabinoid receptor 1 (CB). The endocannabinoid-like compounds oleoylethanolamine (OEA) and palmitoylethanolamine (PEA) play an important role in digestive regulation, and we hypothesized they would also modulate intestinal permeability. Transepithelial electrical resistance (TEER) was measured in human Caco-2 cells to assess permeability after application of OEA and PEA and relevant antagonists. Read More

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http://dx.doi.org/10.1096/fj.201500132DOI Listing
February 2017
16 Reads

A novel microflow LC-MS method for the quantitation of endocannabinoids in serum.

J Chromatogr B Analyt Technol Biomed Life Sci 2016 Oct 22;1033-1034:271-277. Epub 2016 Aug 22.

Colorado State University, Proteomics and Metabolomics Facility, 2021 Campus Delivery, Fort Collins, CO, 80523, USA. Electronic address:

Endocannabinoids (ECs) represent a class of endogenous, small molecules that bind and activate the G-protein coupled EC receptors. They are involved in a variety of fundamental biological processes and are associated with many disease states. Endocannabinoids are often present in complex matrices and at low concentrations, complicating their measurement. Read More

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http://dx.doi.org/10.1016/j.jchromb.2016.08.035DOI Listing
October 2016
7 Reads

Mast Cell - Glia Dialogue in Chronic Pain and Neuropathic Pain: Blood-Brain Barrier Implications.

Authors:
Stephen D Skaper

CNS Neurol Disord Drug Targets 2016 ;15(9):1072-1078

Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Largo "E. Meneghetti" 2, 35131 Padua, Italy.

Mast cells and microglia, working singly and in partnership, produce proinflammatory agents which play key roles in a wide array of nervous system disorders. Such neuroinflammatory settings may compromise integrity of both the blood-nerve barrier and blood-brain barrier (BBB) and blood-spinal cord barrier. While both belong to the innate immune system mast cells are far more ubiquitous, are resident in peripheral nerves and the central nervous system, and can influence blood-nerve barrier characteristics. Read More

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October 2017
4 Reads

The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations.

Br J Pharmacol 2017 06 29;174(11):1349-1365. Epub 2016 Sep 29.

Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy.

Palmitoylethanolamide (PEA) has emerged as a potential nutraceutical, because this compound is naturally produced in many plant and animal food sources, as well as in cells and tissues of mammals, and endowed with important neuroprotective, anti-inflammatory and analgesic actions. Several efforts have been made to identify the molecular mechanism of action of PEA and explain its multiple effects both in the central and the peripheral nervous system. Here, we provide an overview of the pharmacology, efficacy and safety of PEA in neurodegenerative disorders, pain perception and inflammatory diseases. Read More

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http://dx.doi.org/10.1111/bph.13580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429331PMC
June 2017
58 Reads

Efficacy of ultra-micronized palmitoylethanolamide (um-PEA) in geriatric patients with chronic pain: study protocol for a series of N-of-1 randomized trials.

Trials 2016 07 29;17:369. Epub 2016 Jul 29.

Geriatric Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Via Pace 9, 20122, Milan, Italy.

Background: Chronic pain in older people is highly prevalent, often underestimated, and associated with adverse outcomes. Most available analgesic drugs are often either ineffective or not tolerated, with many side effects. Palmitoylethanolamide (PEA) is an endogenous widely distributed N-acylethanolamina involved in neuroinflammation and pain-generating processes. Read More

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http://dx.doi.org/10.1186/s13063-016-1496-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966710PMC
July 2016
6 Reads

PEA and luteolin synergistically reduce mast cell-mediated toxicity and elicit neuroprotection in cell-based models of brain ischemia.

Brain Res 2016 10 14;1648(Pt A):409-417. Epub 2016 Jul 14.

Division of Pharmacology, Department of Molecular and Translational Medicine, National Institute of Neuroscience, University of Brescia, Italy; IRCCS San Camillo, Venezia, Italy. Electronic address:

The combination of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the family of the N-acylethanolamines, and the flavonoid luteolin has been found to exert neuroprotective activities in a variety of mouse models of neurological disorders, including brain ischemia. Indirect findings suggest that the two molecules can reduce the activation of mastocytes in brain ischemia, thus modulating crucial cells that trigger the inflammatory cascade. Though, no evidence exists about a direct effect of PEA and luteolin on mast cells in experimental models of brain ischemia, either used separately or in combination. Read More

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http://dx.doi.org/10.1016/j.brainres.2016.07.014DOI Listing
October 2016
3 Reads

Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

Angew Chem Int Ed Engl 2016 09 12;55(37):11193-11197. Epub 2016 Jul 12.

Department of Drug Discovery and Development, Fondazione Istituto Italiano di Tecnologia, via Morego 30, 16163 Genoa, Italy.

Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. Read More

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http://dx.doi.org/10.1002/anie.201603746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009002PMC
September 2016
4 Reads

Ultramicronized palmitoylethanolamide (PEA-um(®)) in the treatment of idiopathic pulmonary fibrosis.

Pharmacol Res 2016 09 8;111:405-412. Epub 2016 Jul 8.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy; Department of Pharmacological and Physiological Science, Saint Louis University, Saint Louis, MO, USA. Electronic address:

Pulmonary fibrosis is a chronic condition characterized by progressive scarring of lung parenchyma. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (PEA-um(®)), an endogenous fatty acid amide, in mice subjected to idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis was induced in male mice by a single intratracheal administration of saline with bleomycin sulphate (1mg/kg body weight) in a volume of 100μL. Read More

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http://dx.doi.org/10.1016/j.phrs.2016.07.010DOI Listing
September 2016
4 Reads

Assay of NAPE-PLD Activity.

Methods Mol Biol 2016 ;1412:123-30

Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy.

N-acyl-phosphatidylethanolamine (NAPE)-hydrolyzing phospholipase D (NAPE-PLD) is a prominent enzyme involved in the biosynthesis of fatty acid amides (FAAs), a family of bioactive lipids including anandamide (AEA) as the prototypical member. Here, we describe a NAPE-PLD assay based on radioactive substrates and product separation by thin-layer chromatography (TLC). Read More

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http://dx.doi.org/10.1007/978-1-4939-3539-0_13DOI Listing
December 2017
13 Reads

Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: a randomized, double-blind, placebo-controlled trial.

Pain 2016 09;157(9):2097-103

aSpinal Cord Injury Centre of Western Denmark, Department of Neurology, Regional Hospital of Viborg, Viborg, Denmark bClinic for Spinal Cord Injuries, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark cDepartment of Clinical Medicine, University of Bergen, Bergen, Norway dThe Autonomic Unit, National Hospital for Neurology and Neurosurgery, University College London, Queen Square, United Kingdom ePain Research, Department of Surgery and Cancer, Imperial College, London, United Kingdom fHammel Neurorehabilitation and Research Centre, Hammel, Denmark gDepartment of Neurology, Aalborg University Hospital, Aalborg, Denmark hDanish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Neuropathic pain and spasticity after spinal cord injury (SCI) represent significant problems. Palmitoylethanolamide (PEA), a fatty acid amide that is produced in many cells in the body, is thought to potentiate the action of endocannabinoids and to reduce pain and inflammation. This randomized, double-blind, placebo-controlled, parallel multicenter study was performed to investigate the effect of ultramicronized PEA (PEA-um) as add-on therapy on neuropathic pain in individuals with SCI. Read More

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http://dx.doi.org/10.1097/j.pain.0000000000000623DOI Listing
September 2016
20 Reads

Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy.

Br J Clin Pharmacol 2016 10 29;82(4):932-42. Epub 2016 Jun 29.

Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87, Umeå, Sweden.

Palmitoylethanolamide (PEA) has been suggested to have useful analgesic properties and to be devoid of unwanted effects. Here, we have examined critically this contention, and discussed available data concerning the pharmacokinetics of PEA and its formulation. Sixteen clinical trials, six case reports/pilot studies and a meta-analysis of PEA as an analgesic have been published in the literature. Read More

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http://dx.doi.org/10.1111/bcp.13020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094513PMC
October 2016
4 Reads

Palmitoylethanolamide Modulates Inflammation-Associated Vascular Endothelial Growth Factor (VEGF) Signaling via the Akt/mTOR Pathway in a Selective Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α)-Dependent Manner.

PLoS One 2016 24;11(5):e0156198. Epub 2016 May 24.

Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza University of Rome, Rome, Italy.

Background And Aim: Angiogenesis is emerging as a pivotal process in chronic inflammatory pathologies, promoting immune infiltration and prompting carcinogenesis. Ulcerative Colitis (UC) and Crohn's Disease (CD) represent paradigmatic examples of intestinal chronic inflammatory conditions in which the process of neovascularization correlates with the severity and progression of the diseases. Molecules able to target the angiogenesis have thus the potential to synergistically affect the disease course. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156198PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878779PMC
July 2017
8 Reads

Plasma concentrations of oleoylethanolamide and other acylethanolamides are altered in alcohol-dependent patients: effect of length of abstinence.

Addict Biol 2017 Sep 22;22(5):1366-1377. Epub 2016 May 22.

Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.

Acylethanolamides are a family of endogenous lipid mediators that are involved in physiological and behavioral processes associated with addiction. Recently, oleoylethanolamide (OEA) has been reported to reduce alcohol intake and relapse in rodents but the contribution of OEA and other acylethanolamides in alcohol addiction in humans is unknown. The present study is aimed to characterize the plasma acylethanolamides in alcohol dependence. Read More

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http://doi.wiley.com/10.1111/adb.12408
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http://dx.doi.org/10.1111/adb.12408DOI Listing
September 2017
28 Reads

Endocannabinoid-related lipids are increased during an episode of cyclic vomiting syndrome.

Neurogastroenterol Motil 2016 Sep 20;28(9):1409-18. Epub 2016 Apr 20.

Neuroscience Research Center, Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.

Background: The endocannabinoid system and the hypothalamic-pituitary-adrenal axis are important neuromodulators of nausea and vomiting. This led us to hypothesize that patients with cyclic vomiting syndrome (CVS) have lower serum endocannabinoids (eCBs) and higher salivary cortisol and alpha amylase.

Methods: Serum eCBs and related lipids, N-oleoylethanolamine (OEA) and N-palmitoylethanolamide (PEA), and salivary cortisol, and alpha amylase (index of sympathetic nervous system activity) were measured in 22 CVS patients (age 40 ± 11, female = 17) in the well and sick phases and 12 matched controls (age 37 ± 12, female = 10). Read More

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http://dx.doi.org/10.1111/nmo.12843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002231PMC
September 2016

A new co-micronized composite containing palmitoylethanolamide and polydatin shows superior oral efficacy compared to their association in a rat paw model of carrageenan-induced inflammation.

Eur J Pharmacol 2016 Jul 16;782:107-18. Epub 2016 Apr 16.

Department of Biological and Environmental Sciences, University of Messina, University of Messina, Italy; Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd, St Louis, MO 63104, USA. Electronic address:

Palmitoylethanolamide (PEA), a special food for medical purposes, has anti-inflammatory and neuroprotective effects. Nevertheless, PEA lacks direct ability to prevent free radical formation. Polydatin (PLD), a natural precursor of resveratrol, has antioxidant activity. Read More

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http://dx.doi.org/10.1016/j.ejphar.2016.03.033DOI Listing
July 2016
23 Reads

2-pentadecyl-2-oxazoline: Identification in coffee, synthesis and activity in a rat model of carrageenan-induced hindpaw inflammation.

Pharmacol Res 2016 06 12;108:23-30. Epub 2016 Apr 12.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. Electronic address:

N-acylethanolamines (NAEs) comprise a family of bioactive lipid molecules present in animal and plant tissues, with N-palmitoylethanolamine (PEA) having received much attention owing to its anti-inflammatory, analgesic and neuroprotective activities. 2-Pentadecyl-2-oxazoline (PEA-OXA), the oxazoline of PEA, reportedly modulates activity of N-acylethanolamine-hydrolyzing acid amidase (NAAA), which catabolizes PEA. Because PEA is produced on demand and exerts pleiotropic effects on non-neuronal cells implicated in neuroinflammation, modulating the specific amidases for NAEs (NAAA in particular) could be a way to preserve PEA role in maintaining cellular homeostasis through its rapid on-demand synthesis and equally rapid degradation. Read More

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http://dx.doi.org/10.1016/j.phrs.2016.04.007DOI Listing
June 2016
8 Reads

Bisphenol A Induces Fatty Liver by an Endocannabinoid-Mediated Positive Feedback Loop.

Endocrinology 2016 05 25;157(5):1751-63. Epub 2016 Mar 25.

Dipartimento di Scienze della Vita e dell'Ambiente (A.M., F.M., G.G., O.C.), Università Politecnica delle Marche, 60131 Ancona, Italy; Endocannabinoid Research Group (A.M., C.S., M.A., V.D.), Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli (NA), Italy; Dipartimento di Biomedicina Comparata e Alimentazione (G.R.), Universitá degli Studi di Padova, 35020 Legnaro (PD), Italy; Department of Bioengineering (C.S., D.R.O.), Imperial College London, London SW7 2AZ, United Kingdom; and Istituto Nazionale Biostrutture e Biosistemi (F.M., O.C.), 00136, Roma, Italy.

The xenoestrogen bisphenol A (BPA) is a widespread plasticizer detectable within several ecosystems. BPA is considered a metabolic disruptor, affecting different organs; however, little is known about its mechanism of action in the liver, in which it triggers triglyceride accumulation. Adult zebrafish (Danio rerio) exposed to BPA developed hepatosteatosis, which was associated with an increase in the liver levels of the obesogenic endocannabinoids 2-arachidonoylglycerol and anandamide and a concomitant decrease in palmitoylethanolamide. Read More

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http://dx.doi.org/10.1210/en.2015-1384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6285285PMC
May 2016
15 Reads

N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release.

Sci Rep 2016 Mar 23;6:23481. Epub 2016 Mar 23.

Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA.

Cortical spreading depression (CSD), a wave of neuronal depolarization in the cerebral cortex following traumatic brain injury or cerebral ischemia, significantly aggravates brain damage. Here, we tested whether N-palmitoylethanolamine (PEA), a substance that effectively reduces lesion volumes and neurological deficits after ischemic stroke, influences CSD. CSD was elicited chemically in adult rats and occurrence, amplitude, duration and propagation velocity of CSD was determined prior to and for 6 hours after intraperitoneal injection of PEA. Read More

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http://dx.doi.org/10.1038/srep23481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804239PMC
March 2016
2 Reads

Endovanilloid control of pain modulation by the rostroventromedial medulla in an animal model of diabetic neuropathy.

Neuropharmacology 2016 08 8;107:49-57. Epub 2016 Mar 8.

Institute of Biomolecular Chemistry of the National Research Council (ICB-CNR), Naples, Italy.

The involvement of transient receptor vanilloid type-1 (TRPV1) channels in pain modulation by the brain remains understudied. The rostroventromedial medulla (RVM) plays a key role in conveying to the spinal cord pain modulatory influences triggered in higher brain centres, with co-existence of inhibitory (antinociceptive) and facilitatory (pronociceptive) effects. In spite of some reports of TRPV1 expression in the RVM, it remains unknown if endovanilloid signalling plays a direct role in local pain modulation. Read More

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http://dx.doi.org/10.1016/j.neuropharm.2016.03.007DOI Listing

Fatty acid amide hydrolase inhibitors confer anti-invasive and antimetastatic effects on lung cancer cells.

Oncotarget 2016 Mar;7(12):15047-64

Institute of Toxicology and Pharmacology, Rostock University Medical Center, Rostock, Germany.

Inhibition of endocannabinoid degradation has been suggested as tool for activation of endogenous tumor defense. One of these strategies lies in blockade of fatty acid amide hydrolase (FAAH) which catalyzes the degradation of endocannabinoids (anandamide [AEA], 2-arachidonoylglycerol [2-AG]) and endocannabinoid-like substances (N-oleoylethanolamine [OEA], N-palmitoylethanolamine [PEA]). This study addressed the impact of two FAAH inhibitors (arachidonoyl serotonin [AA-5HT], URB597) on A549 lung cancer cell metastasis and invasion. Read More

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http://dx.doi.org/10.18632/oncotarget.7592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924770PMC
March 2016
42 Reads

Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy.

Proc Natl Acad Sci U S A 2016 Mar 29;113(11):3060-5. Epub 2016 Feb 29.

Department of Neurology and Psychiatry, University of Rome Sapienza, 00185 Rome, Italy;

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons that leads to progressive paralysis of skeletal muscle. Studies of ALS have revealed defects in expression of acetylcholine receptors (AChRs) in skeletal muscle that occur even in the absence of motor neuron anomalies. The endocannabinoid palmitoylethanolamide (PEA) modified the clinical conditions in one ALS patient, improving muscle force and respiratory efficacy. Read More

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http://dx.doi.org/10.1073/pnas.1600251113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801305PMC
March 2016
6 Reads

Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway.

Phytother Res 2016 Jun 1;30(6):963-70. Epub 2016 Mar 1.

Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza University of Rome, Rome, Italy.

Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve intestinal inflammation. We aimed at evaluating its antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco-2 cell line. Caco-2 cells were treated with increasing concentrations of PEA (0. Read More

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http://dx.doi.org/10.1002/ptr.5601DOI Listing
June 2016
11 Reads

Endocannabinoid concentrations in hair are associated with PTSD symptom severity.

Psychoneuroendocrinology 2016 May 12;67:198-206. Epub 2016 Feb 12.

Clinical & Biological Psychology, Institute of Psychology & Education, Ulm University, Albert-Einstein-Allee 47, 89069 Ulm, Germany.

The endocannabinoid system has been implicated in the regulation of the stress response, fear memory formation, and inflammatory processes. Posttraumatic stress disorder (PTSD) can result from exposure to extreme stress and is characterized by strong, associative memories for the traumatic events experienced. Furthermore, an elevated physical disease risk has been observed in PTSD, likely to be mediated by inflammatory processes. Read More

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http://dx.doi.org/10.1016/j.psyneuen.2016.02.010DOI Listing
May 2016
18 Reads

Elevated Systemic Levels of Endocannabinoids and Related Mediators Across the Menstrual Cycle in Women With Endometriosis.

Reprod Sci 2016 08 17;23(8):1071-9. Epub 2016 Feb 17.

Division of Genetics and Cell Biology, Reproductive Sciences Laboratory, IRCCS Ospedale San Raffaele, Milan, Italy

Cannabinoids and modulators of the endocannabinoid system affect specific mechanisms that are critical to the establishment and development of endometriosis. The aim of this study was to measure the systemic levels of endocannabinoids and related mediators in women with and without endometriosis and to investigate whether such levels correlated with endometriosis-associated pain. Plasma and endometrial biopsies were obtained from women with a laparoscopic diagnosis of endometriosis (n = 27) and no endometrial pathology (n = 29). Read More

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http://dx.doi.org/10.1177/1933719116630414DOI Listing
August 2016
22 Reads

Effects of chronic exercise on the endocannabinoid system in Wistar rats with high-fat diet-induced obesity.

J Physiol Biochem 2016 Jun 15;72(2):183-99. Epub 2016 Feb 15.

Univ Lille - EA 7369, URePSS - Unité de Recherche Pluridisciplinaire Sport, Santé, Société - Equipe Activité Muscle, Santé, Eurasport, 413 rue Eugène Avinée, 59120, Loos, France.

The endocannabinoid system is dysregulated during obesity in tissues involved in the control of food intake and energy metabolism. We examined the effect of chronic exercise on the tissue levels of endocannabinoids (eCBs) and on the expression of genes coding for cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) (Cnr1 and Cnr2, respectively) in the subcutaneous (SAT) and visceral adipose tissues and in the soleus and extensor digitorim longus (EDL) muscles, in rats fed with standard or high-fat diet. Twenty-eight male Wistar rats were placed on high-fat diet or standard diet (HFD and Ctl groups, respectively) during 12 weeks whereafter half of each group was submitted to an exercise training period of 12 weeks (HFD + training and Ctl + training). Read More

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http://dx.doi.org/10.1007/s13105-016-0469-5DOI Listing
June 2016
27 Reads

Nanoparticles prolong N-palmitoylethanolamide anti-inflammatory and analgesic effects in vivo.

Colloids Surf B Biointerfaces 2016 May 1;141:311-317. Epub 2016 Feb 1.

Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università degli Studi di Camerino, Piazza dei Costanti, 62032 Camerino, Italy. Electronic address:

N-Palmitoylethanolamide showed great therapeutic potential in the treatment of inflammation and pain but its unfavourable pharmacokinetics properties will hinder its use in the clinical practice. A nanotechnology-based formulation was developed to enhance the probability of N-palmitoylethanolamide therapeutic success, especially in skin disease management. Lipid nanoparticles were produced and characterized to evaluate their mean size, ζ-potential, thermal behaviour, and morphology. Read More

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http://dx.doi.org/10.1016/j.colsurfb.2016.01.058DOI Listing
May 2016
2 Reads

Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis.

Neurotherapeutics 2016 Apr;13(2):428-38

Department of Neurosciences, Reproductive and Odontostomatological Sciences, "Federico II" University of Naples, Naples, Italy.

Palmitoylethanolamide (PEA) is an endogenous lipid mediator known to reduce pain and inflammation. However, only limited clinical studies have evaluated the effects of PEA in neuroinflammatory and neurodegenerative diseases. Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system. Read More

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http://dx.doi.org/10.1007/s13311-016-0420-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824021PMC
April 2016
2 Reads

MALDI MSI analysis of lipid changes in living skin equivalents in response to emollient creams containing palmitoylethanolamide.

Methods 2016 07 2;104:93-100. Epub 2016 Feb 2.

Centre for Mass Spectrometry Imaging, Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, United Kingdom. Electronic address:

Mass spectrometry imaging (MSI) is a powerful tool for the study of intact tissue sections. The use of matrix-assisted laser desorption/ionisation (MALDI) MSI for the study of the distribution and effect of emollient treatment on sections of reconstructed living skin equivalents during their development and maturation is described. Living skin equivalent (LSE) samples were obtained at 14days development, re-suspended in maintenance medium and incubated for 24h after delivery. Read More

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http://dx.doi.org/10.1016/j.ymeth.2016.02.001DOI Listing
July 2016
6 Reads

Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO.

Shock 2016 08;46(2):202-13

*Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, Messina, Italy †Department of Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy ‡Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri.

Myocardial infarction is the leading cause of death, occurs after prolonged ischemia of the coronary arteries. Restore blood flow is the first intervention help against heart attack. However, reperfusion of the arteries leads to ischemia/reperfusion injury (I/R). Read More

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http://dx.doi.org/10.1097/SHK.0000000000000578DOI Listing
August 2016
5 Reads

Lipidomic Analysis of Endocannabinoid Signaling: Targeted Metabolite Identification and Quantification.

Neural Plast 2016 29;2016:2426398. Epub 2015 Dec 29.

Department of Biological Sciences, Center for Plant Lipid Research, University of North Texas, Denton, TX 76203, USA.

The endocannabinoids N-arachidonoylethanolamide (or anandamide, AEA) and 2-arachidonoylglycerol (2-AG) belong to the larger groups of N-acylethanolamines (NAEs) and monoacylglycerol (MAG) lipid classes, respectively. They are biologically active lipid molecules that activate G-protein-coupled cannabinoid receptors found in various organisms. After AEA and 2-AG were discovered in the 1990s, they have been extensively documented to have a broad range of physiological functions. Read More

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http://dx.doi.org/10.1155/2016/2426398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709765PMC
November 2016
2 Reads

Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis.

Pain Physician 2016 Feb;19(2):11-24

University of L'Aquila, and Paolo Procacci Foundation, Via Tacito 7, 00193 Roma, Italy.

Background: A growing body of evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of mast cells and glial cells, and production of inflammatory mediators in the peripheral and central nervous systems, has an important role in the induction and maintenance of chronic pain. These findings support the notion that new therapeutic opportunities for chronic pain might be based on anti-inflammatory and pro-resolving mediators that act on immune cells, in particular mast cells and glia, to mitigate or abolish neuroinflammation. Among anti-inflammatory and pro-resolving lipid mediators, palmitoylethanolamide (PEA) has been reported to down-modulate mast cell activation and to control glial cell behaviors. Read More

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February 2016
6 Reads

Responses of peripheral endocannabinoids and endocannabinoid-related compounds to hedonic eating in obesity.

Eur J Nutr 2016 Jun 12;55(4):1799-805. Epub 2016 Jan 12.

Department of Psychiatry, University of Naples SUN, Naples, Italy.

Purpose: Hedonic eating occurs independently from homeostatic needs prompting the ingestion of pleasurable foods that are typically rich in fat, sugar and/or salt content. In normal weight healthy subjects, we found that before hedonic eating, plasma levels of 2-arachidonoylglycerol (2-AG) were higher than before nonhedonic eating, and although they progressively decreased after food ingestion in both eating conditions, they were significantly higher in hedonic eating. Plasma levels of anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), instead, progressively decreased in both eating conditions without significant differences. Read More

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http://link.springer.com/10.1007/s00394-016-1153-9
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http://dx.doi.org/10.1007/s00394-016-1153-9DOI Listing
June 2016
1 Read