BACKGROUND AND PURPOSE:

Palmitoylethanolamide is both an endogenous lipid mediator chemically related to the endocannabinoid anandamide and a food component contained in over-the-counter preparations promoted for inflammatory bowel disease. Additionally, palmitoylethanolamide acts via targets, i.e. cannabinoid (CB1 and CB2 ) receptors, transient receptor potential vanilloid type-1 (TRPV1), peroxisomal proliferator activated receptor α (PPARα) and orphan G protein-coupled receptor 55 (GPR55) involved in the control of intestinal inflammation. Here, we investigated the effect of PEA in a murine model of colitis.

EXPERIMENTAL APPROACH:

Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters and by histology; intestinal permeability by a fluorescent method; colonic cell proliferation by immunohistochemistry; palmitoylethanolamide and endocannabinoid levels by chromatography-mass spectrometry; receptor and enzyme mRNA expression by quantitative reverse transcription-PCR.

KEY RESULTS:

DNBS administration caused inflammatory damage, increased colonic levels of palmitoylethanolamide and endocannabinoids, down-regulation of TRPV1 and GPR55 mRNA expression (with no changes in CB1 , CB2 , and PPARα). Exogenous palmitoylethanolamide (intraperitoneally and/or orally, 1 mg kg-1 ) attenuated inflammation and intestinal permeability, stimulated colonic cell proliferation and increased colonic TRPV1 and CB1 receptor expression. The anti-inflammatory effect of PEA was attenuated or abrogated by CB2 receptor, GPR55 or PPARα antagonists and further increased by the TRPV1 antagonist capsazepine.

CONCLUSION AND IMPLICATIONS:

Palmitoylethanolamide improves murine colitis, the effect being mediated by CB2 receptors, GPR55 and PPARα, and modulated by TRPV1 channels.
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