Elevation of arachidonoylethanolamide levels by activation of the endocannabinoid system protects against colitis and ameliorates remote organ lesions in mice

Zhao, Xiaolin; Liang, Peng; Liu, Jin; Jiang, Haixia; Fan, Xiaoshuai; Chen, Guo; Zhou, Cheng

doi:10.3892/etm.2017.5222

Cited by 8 publications

(7 citation statements)

References 24 publications

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“…One study has suggested that therapeutic FAAH inhibition may have additional benefits over prophylactic administration, although this remains to be replicated. 98 Despite several studies demonstrating a benefit of FAAH inhibition, findings are not unanimous. One study demonstrated that PF3845 is effective at ameliorating colitis in the TNBS model but not the DSS model.…”

Section: In Vivo Studiesmentioning

confidence: 99%

Cannabis, Cannabinoids, and the Endocannabinoid System—Is there Therapeutic Potential for Inflammatory Bowel Disease?

Ambrose

Simmons

2018

Journal of Crohn's and Colitis

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Cannabis sativa and its extracts have been used for centuries, both medicinally and recreationally. There is accumulating evidence that exogenous cannabis and related cannabinoids improve symptoms associated with inflammatory bowel disease [IBD], such as pain, loss of appetite, and diarrhoea. In vivo , exocannabinoids have been demonstrated to improve colitis, mainly in chemical models. Exocannabinoids signal through the endocannabinoid system, an increasingly understood network of endogenous lipid ligands and their receptors, together with a number of synthetic and degradative enzymes and the resulting products. Modulating the endocannabinoid system using pharmacological receptor agonists, genetic knockout models, or inhibition of degradative enzymes have largely shown improvements in colitis in vivo . Despite these promising experimental results, this has not translated into meaningful benefits for human IBD in the few clinical trials which have been conducted to date, the largest study being limited by poor medication tolerance due to the Δ 9 -tetrahydrocannabinol component. This review article synthesises the current literature surrounding the modulation of the endocannabinoid system and administration of exocannabinoids in experimental and human IBD. Findings of clinical surveys and studies of cannabis use in IBD are summarised. Discrepancies in the literature are highlighted together with identifying novel areas of interest.

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Section: In Vivo Studiesmentioning

confidence: 99%

Cannabis, Cannabinoids, and the Endocannabinoid System—Is there Therapeutic Potential for Inflammatory Bowel Disease?

Ambrose

Simmons

2018

Journal of Crohn's and Colitis

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“…As global FAAH inhibition is associated with suppression of colonic inflammation [ 89 – 97 ], we administered the FAAH inhibitor intracerebroventricularly (icv) to be able to establish the importance of central FAAH inhibition on colitis-induced anxiety. Rats underwent intracranial cannulations as previously described [ 50 ].…”

Section: Methodsmentioning

confidence: 99%

Comorbid anxiety-like behavior in a rat model of colitis is mediated by an upregulation of corticolimbic fatty acid amide hydrolase

Vecchiarelli

Morena

Keenan

et al. 2021

Neuropsychopharmacol.

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Peripheral inflammatory conditions, including those localized to the gastrointestinal tract, are highly comorbid with psychiatric disorders such as anxiety and depression. These behavioral symptoms are poorly managed by conventional treatments for inflammatory diseases and contribute to quality of life impairments. Peripheral inflammation is associated with sustained elevations in circulating glucocorticoid hormones, which can modulate central processes, including those involved in the regulation of emotional behavior. The endocannabinoid (eCB) system is exquisitely sensitive to these hormonal changes and is a significant regulator of emotional behavior. The impact of peripheral inflammation on central eCB function, and whether this is related to the development of these behavioral comorbidities remains to be determined. To examine this, we employed the trinitrobenzene sulfonic acid-induced model of colonic inflammation (colitis) in adult, male, Sprague Dawley rats to produce sustained peripheral inflammation. Colitis produced increases in behavioral measures of anxiety and elevations in circulating corticosterone. These alterations were accompanied by elevated hydrolytic activity of the enzyme fatty acid amide hydrolase (FAAH), which hydrolyzes the eCB anandamide (AEA), throughout multiple corticolimbic brain regions. This elevation of FAAH activity was associated with broad reductions in the content of AEA, whose decline was driven by central corticotropin releasing factor type 1 receptor signaling. Colitis-induced anxiety was reversed following acute central inhibition of FAAH, suggesting that the reductions in AEA produced by colitis contributed to the generation of anxiety. These data provide a novel perspective for the pharmacological management of psychiatric comorbidities of chronic inflammatory conditions through modulation of eCB signaling.

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“…Endocannabinoids can also display anti-inflammatory effects in different AIDs; however, their pharmacological potential is still debated. The exogenous supplementation of either COX-2 inhibitors [130], cannabinoid receptor agonists [65,66], or endocannabinoid degradation inhibitors [65,[130][131][132] increased the levels of anti-rheumatic N-acylethanolamines. In the same way, in some diseases, the modulation of S1P pathway could be accomplished indirectly and not using exogenous S1P.…”

Section: Anti-inflammatory Lipids and Their Therapeutic Potentialmentioning

confidence: 99%

Functional Lipids in Autoimmune Inflammatory Diseases

Dei

Roda

et al. 2020

IJMS

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Lipids are apolar small molecules known not only as components of cell membranes but also, in recent literature, as modulators of different biological functions. Herein, we focused on the bioactive lipids that can influence the immune responses and inflammatory processes regulating vascular hyperreactivity, pain, leukocyte trafficking, and clearance. In the case of excessive pro-inflammatory lipid activity, these lipids also contribute to the transition from acute to chronic inflammation. Based on their biochemical function, these lipids can be divided into different families, including eicosanoids, specialized pro-resolving mediators, lysoglycerophospholipids, sphingolipids, and endocannabinoids. These bioactive lipids are involved in all phases of the inflammatory process and the pathophysiology of different chronic autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, type-1 diabetes, and systemic lupus erythematosus.

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Elevation of arachidonoylethanolamide levels by activation of the endocannabinoid system protects against colitis and ameliorates remote organ lesions in mice

Cited by 8 publications

References 24 publications

Cannabis, Cannabinoids, and the Endocannabinoid System—Is there Therapeutic Potential for Inflammatory Bowel Disease?

Cannabis, Cannabinoids, and the Endocannabinoid System—Is there Therapeutic Potential for Inflammatory Bowel Disease?

Comorbid anxiety-like behavior in a rat model of colitis is mediated by an upregulation of corticolimbic fatty acid amide hydrolase

Functional Lipids in Autoimmune Inflammatory Diseases

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