Orally administered oleoylethanolamide protects mice from focal cerebral ischemic injury by activating peroxisome proliferator-activated receptor α

Zhou, Yu; Yang, Lichao; Ma, Ang; Zhang, Xuemei; Li, Weijie; Yang, Wu; Chen, Caixia; Jin, Xin

doi:10.1016/j.neuropharm.2012.03.008

Cited by 67 publications

(82 citation statements)

References 46 publications

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“…Human and animal in vivo data have shown increases in neurological and circulating plasma levels of AEA, 2-AG, OEA and PEA after stroke (Schabitz et al 2002;Hillard 2008;Naccarato et al 2010). As in other cardiovascular disorders, the hypothesis is that upregulation of the endocannabinoid system is protective in stroke, and this is supported by numerous studies showing that 2-AG (Wang et al 2009), AEA (Wang et al 2009) as well as the endocannabinoid-like compounds, OEA (Sun et al 2007;Zhou et al 2012) and PEA (Schomacher et al 2008;Garg et al 2010;Ahmad et al 2012b), offer protection against ischaemic/reperfusion injury. N-acylethanolamine compounds such as lauroylethanolamide and linoleoylethanolamide have also been shown to be protective against stroke (Garg et al 2011).…”

Section: Endocannabinoids and Cerebral Ischaemia/strokementioning

confidence: 93%

Endocannabinoids and the Cardiovascular System in Health and Disease

O’Sullivan

2015

Handbook of Experimental Pharmacology

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The endocannabinoid system is widely distributed throughout the cardiovascular system. Endocannabinoids play a minimal role in the regulation of cardiovascular function in normal conditions, but are altered in most cardiovascular disorders. In shock, endocannabinoids released within blood mediate the associated hypotension through CB(1) activation. In hypertension, there is evidence for changes in the expression of CB(1), and CB(1) antagonism reduces blood pressure in obese hypertensive and diabetic patients. The endocannabinoid system is also upregulated in cardiac pathologies. This is likely to be cardioprotective, via CB(2) and CB(1) (lesser extent). In the vasculature, endocannabinoids cause vasorelaxation through activation of multiple target sites, inhibition of calcium channels, activation of potassium channels, NO production and the release of vasoactive substances. Changes in the expression or function of any of these pathways alter the vascular effect of endocannabinoids. Endocannabinoids have positive (CB(2)) and negative effects (CB(1)) on the progression of atherosclerosis. However, any negative effects of CB(1) may not be consequential, as chronic CB(1) antagonism in large scale human trials was not associated with significant reductions in atheroma. In neurovascular disorders such as stroke, endocannabinoids are upregulated and protective, involving activation of CB(1), CB(2), TRPV1 and PPARα. Although most of this evidence is from preclinical studies, it seems likely that cannabinoid-based therapies could be beneficial in a range of cardiovascular disorders.

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Section: Endocannabinoids and Cerebral Ischaemia/strokementioning

confidence: 93%

Endocannabinoids and the Cardiovascular System in Health and Disease

O’Sullivan

2015

Handbook of Experimental Pharmacology

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“…1) is an endocannabinoid analogy that belongs to a family of endogenous acylethanolamides [2]. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of reward-related behaviors [1,8]. Systemic administration of OEA to rats results in elevated OEA plasma levels, as has also been reported in patients with post-traumatic stress disorder [9].…”

Section: Introductionmentioning

confidence: 90%

Involvement of norepinephrine and serotonin system in antidepressant-like effects of oleoylethanolamide in the mice models of behavior despair

Sun

et al. 2015

Neuroscience Letters

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“…Thus, the effects observed here upon um-PEA administration can be due to PEA activating its molecular targets, and also to PEA favoring the actions of other NAEs (e.g., AEA and OEA). Indeed, anti-inflammatory, neuroprotective, and analgesic effects have been reported for AEA and OEA in several preclinical models [69][70][71][72][73].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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. Although subcutaneous administration of interferon (IFN)-β1a is approved as first-line therapy for the treatment of relapsing-remitting MS (RR-MS), its commonly reported adverse events (AEs) such as pain, myalgia, and erythema at the injection site, deeply affect the quality of life (QoL) of patients with MS. In this randomized, double-blind, placebocontrolled study, we tested the effect of ultramicronized PEA (um-PEA) added to IFN-β1a in the treatment of clinically defined RR-MS. The primary objectives were to estimate whether, with um-PEA treatment, patients with MS perceived an improvement in pain and a decrease of the erythema width at the IFN-β1a injection site in addition to an improvement in their QoL. The secondary objectives were to evaluate the effects of um-PEA on circulating interferon-γ, tumor necrosis factor-α, and interleukin-17 serum levels, N-acylethanolamine plasma levels, Expanded Disability Status Scale (EDSS) progression, and safety and tolerability after 1 year of treatment. Patients with MS receiving um-PEA perceived an improvement in pain sensation without a reduction of the erythema at the injection site. A significant improvement in QoL was observed. No significant difference was reported in EDSS score, and um-PEA was well tolerated. We found a significant increase of palmitoylethanolamide, anandamide and oleoylethanolamide plasma levels, and a significant reduction of interferon-γ, tumor necrosis factor-α, and interleukin-17 serum profile compared with the placebo group. Our results suggest that um-PEA may be considered as an appropriate add-on therapy for the treatment of IFN-β1a-related adverse effects in RR-MS.

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Orally administered oleoylethanolamide protects mice from focal cerebral ischemic injury by activating peroxisome proliferator-activated receptor α

Cited by 67 publications

References 46 publications

Endocannabinoids and the Cardiovascular System in Health and Disease

Endocannabinoids and the Cardiovascular System in Health and Disease

Involvement of norepinephrine and serotonin system in antidepressant-like effects of oleoylethanolamide in the mice models of behavior despair

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

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