Increasing endogenous 2‐arachidonoylglycerol levels counteracts colitis and related systemic inflammation

  title={Increasing endogenous 2‐arachidonoylglycerol levels counteracts colitis and related systemic inflammation},
  author={Mireille Alhouayek and Didier M. Lambert and Nathalie M. Delzenne and Patrice D Cani and Giulio G. Muccioli},
  journal={The FASEB Journal},
  pages={2711 - 2721}
Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions for which new therapeutic approaches are needed. Genetic and pharmacological data point to a protective role of CB1 and CB2 cannabinoid receptor activation in IBD experimental models. Therefore, increasing the endogenous levels of 2‐arachidonoylglycerol, the main full agonist of these receptors, should have beneficial effects on colitis. 2‐Arachidonoylglycerol levels were raised in the trinitrobenzene sulfonic acid (TNBS… 

Manipulation of the Endocannabinoid System in Colitis: A Comprehensive Review

Although manipulation of the endocannabinoid system in murine colitis has proven to be largely beneficial in attenuating inflammation, there is a paucity of human study data, and further research is essential to clearly elucidate the specific mechanisms driving this anti-inflammatory effect for the development of therapeutics to target inflammatory disease such as IBD.

Endocannabinoid System as a Promising Therapeutic Target in Inflammatory Bowel Disease – A Systematic Review

This review summarizes the role of ECS components on intestinal inflammation, suggesting the advantages of cannabinoid-based therapies in inflammatory bowel disease.

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The effect of modulating the CB2 receptor pathway in an acute sepsis mouse model was explored and it was found that HU308 (CB2 receptor agonist) reduced the number of adherent leukocytes in submucosal venules but did not restore muscular and mucosal villi FCD in endotoxemic mice.

Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation

Experimental data suggest that the endocannabinoid system represents a promising target in the treatment of inflammatory bowel diseases, and this assumption is also confirmed by preliminary clinical studies.

The endogenous bioactive lipid prostaglandin D2‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

PGD2‐G could be one of the products from the COX‐2/prostaglandin D synthase axis to exert beneficial effects in colitis, and is shown to be an agonist of the PGD2 receptor 1 (DP1) and that some of the effects of PGD 2‐G were blocked by antagonism of peroxisome proliferator‐activated receptor γ and DP1.

Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6

In macrophages, the newly characterized enzyme α/β-hydrolase domain 6 (ABHD6) controls 2-arachidonoylglycerol (2-AG) levels and thus its pharmacological effects, and this points to ABHD6 as an interesting therapeutic target that should be relevant in treating inflammation-related conditions, and proposes PGD2-G as a bioactive lipid with potential anti-inflammatory properties in vivo.

Therapeutic potential of monoacylglycerol lipase inhibitors.

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

Modulation of the ECS was efficient in ameliorating colitis and increasing the survival rate of the mice, and reducing remote organ changes induced by colitis, suggesting that modulation ofThe ECS is a potential therapeutic approach for IBDs and the associated remote organ lesions.



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It is shown that cannabinoid receptors type 1 (CB1) mediate intrinsic protective signals that counteract proinflammatory responses, and this system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses.

Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitis

The show that activation of the CB2 receptor protects against experimental colitis in mice suggests a role for this receptor in normally limiting the development of colitis, and support the idea that theCB2 receptor may be a possible novel therapeutic target in inflammatory bowel disease.

β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway.

CXCR3 axis: role in inflammatory bowel disease and its therapeutic implication.

While it is demonstrated that antibodies directed against CXCL10 could both prevent the onset and cure of pre-existing colitis in IL-10(-/-) mice, studies by other investigators have shown the efficacy of CXCR3 blockade to mitigate colitis and other inflammatory diseases.

Intestinal anti‐inflammatory activity of UR‐12746, a novel 5‐ASA conjugate, on acute and chronic experimental colitis in the rat

The results suggest that the intestinal anti‐inflammatory activity of UR‐12746 can be attributed to the additive effects exerted by 5‐ASA andUR‐12715, the PAF antagonist compound, that are released in the colonic lumen after reduction of the azo bond by the intestinal bacteria.

Effects of a Cannabinoid Receptor 2 Selective Antagonist on the Inflammatory Reaction to Titanium Particles In Vivo and In Vitro

  • F. ZhouJ. Lu Y. Xu
  • Biology, Medicine
    The Journal of international medical research
  • 2010
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It is shown that macrophages require both interferon-γ (IFN-γ)-mediated and TLR4-mediated signals for the production of NO, which causes inflammation in the intestine and subsequently IBD, which is the result of concerted actions of innate immune signals.