N-Oleoylethanolamine Reduces Inflammatory Cytokines and Adhesion Molecules in TNF-α-induced Human Umbilical Vein Endothelial Cells by Activating CB2 and PPAR-α

Xu, Xudong; Guo, Hong-Fen; Zuo, Jing; Yang, Lichao; Chen, Caixia; Lu, Peng; Wang, Xiaoqing; Lü, Yan; Ye, Rongting; Jin, Xin; Wang, Yiqing

doi:10.1097/fjc.0000000000000413

Cited by 40 publications

(25 citation statements)

References 55 publications

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“…Vascular adhesion molecules and inflammatory cytokines are overexpressed in activated endothelial cells [19,20]. First, we examined whether Hy (Figure S1) protected HMEC-1 cells against LPS-mediated inflammation.…”

Section: Resultsmentioning

confidence: 99%

Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway

Sun

Zhu

Cai

et al. 2017

IJMS

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Endothelial lesion response to injurious stimuli is a necessary step for initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from different marine sources is shown to exhibit anti-inflammatory properties. However, the potential roles and possible molecular mechanisms of Hy in endothelial inflammation have yet to be fully clarified. We showed that Hy significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro-inflammatory cytokines expressions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome proliferator-activated receptor γ (PPAR-γ) and upregulated toll-like receptor 4 (TLR4) expressions in LPS-challenged endothelial cells were prevented by Hy. Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4 expressions and decreases in PPAR-γ levels. Genetic silencing of TLR4 or PPAR-γ agonist pioglitazone obviously abrogated the levels of pro-inflammatory cytokines in LPS-treated HMEC-1 cells. These results suggest that Hy may exert anti-inflammatory actions through the regulation of TLR4 and PPAR-γ dependent on PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent that can potentially relieve or ameliorate endothelial inflammation-associated diseases.

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Section: Resultsmentioning

confidence: 99%

Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway

Sun

Zhu

Cai

et al. 2017

IJMS

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“…OEA also inhibited the nuclear factor kappa-B (NF-kB) pathway in the body. 39 In YT et al's survey, OEA (50 µmol/L) inhibited the TNF-α induced VCAM-1 expression in HUVEC. 40…”

Section: Introductionmentioning

confidence: 96%

Oleoylethanolamide Supplementation Reduces Inflammation and Oxidative Stress in Obese People: A Clinical Trial

Payahoo¹,

Khajebishak²,

Jafarabadi³

et al. 2018

Adv Pharm Bull

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Purpose: Obesity as a serious public health problem worldwide, results in the incidence of many chronic diseases. Obesity has been recognized as a chronic low-grade inflammation disorder. Altered endocannabinoid system tone is also involved in the pathogenesis of obesity. The present study aimed to investigate the effects of oleoylethanolamide supplementation on inflammatory biomarkers and oxidative stress in obese people.Methods: This randomized, double-blind, placebo-controlled clinical trial was carried out on 60 healthy obese people in 2016 in Tabriz, Iran. Eligible subjects were randomly divided into intervention (received daily, two 125 mg OEA capsules) and control groups (the same amounts of starch) and treated for 8 weeks. Blood samples (5 ml) were taken in fasting state at the baseline and at the end of the study. The concentrations of MDA and TAS were measured using a spectrophotometer. A high sensitive-C reactive protein level was measured by Immunoturbidimetry assay using the commercial kit. IL-6 and TNF-α levels were assayed by the ELISA method. The differences between groups were assessed by ANCOVA and statistical significance was determined at p<0.05.Results: Analysis was done on 56 participants who continued intervention until the end of the study. A significant decrease in the IL-6 and TNF-α serum concentrations was observed in the intervention group (p<0.001). Changes in other variables were undetectable (p>0.05).Conclusion: The use of OEA as a complementary pharmacotherapy agent could be effective in improving inflammation and oxidative stress in obese people. Future studies are needed to confirm the obtained results.

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“…Although the FAAs examined have been reported to activate CB 2 receptors [28][29][30][31], previous publications have also suggested effects on CB 1 receptors [29], PPAR (PPAR-α, -β and -γ) receptors [10,[31][32][33], and TRPV1 [9,34,35] and TRPM8 [36] ion channels. However, a role for CB 2 receptors has been clearly identified in these studies, which utilised highly selective pharmacological tools [26,27], that is consistent with previous studies [6,7].…”

Section: Discussionmentioning

confidence: 84%

Targeting fatty acid amide hydrolase as a therapeutic strategy for antitussive therapy

et al. 2017

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Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity elevation of endocannabinoids.Primary vagal ganglia neurons, tissue bioassay, electrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents.FAAH inhibition produced antitussive activity in guinea pigs with concomitant plasma elevation of the fatty acid amides -arachidonoylethanolamide (anandamide), palmitoylethanolamide,-oleoylethanolamide and linoleoylethanolamide. Palmitoylethanolamide inhibited tussive stimulus-induced activation of guinea pig airway innervating vagal ganglia neurons, depolarisation of guinea pig and human vagus, and firing of C-fibre afferents. These effects were mediated a cannabinoid CB/G-coupled pathway and activation of protein phosphatase 2A, resulting in increased calcium sensitivity of calcium-activated potassium channels.These findings identify FAAH inhibition as a target for the development of novel, antitussive agents without the undesirable side-effects of direct cannabinoid receptor agonists.

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N-Oleoylethanolamine Reduces Inflammatory Cytokines and Adhesion Molecules in TNF-α-induced Human Umbilical Vein Endothelial Cells by Activating CB2 and PPAR-α

Cited by 40 publications

References 55 publications

Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway

Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway

Oleoylethanolamide Supplementation Reduces Inflammation and Oxidative Stress in Obese People: A Clinical Trial

Targeting fatty acid amide hydrolase as a therapeutic strategy for antitussive therapy

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