Format

Send to

Choose Destination
Br J Pharmacol. 2015 Jan;172(1):142-58. doi: 10.1111/bph.12907. Epub 2014 Dec 1.

Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent.

Author information

1
Department of Pharmacy, University of Naples Federico II, Naples, Italy.

Abstract

BACKGROUND AND PURPOSE:

Palmitoylethanolamide (PEA) acts via several targets, including cannabinoid CB1 and CB2 receptors, transient receptor potential vanilloid type-1 (TRPV1) ion channels, peroxisome proliferator-activated receptor alpha (PPAR α) and orphan G protein-coupled receptor 55 (GRR55), all 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; PEA and endocannabinoid levels by liquid chromatography mass spectrometry; receptor and enzyme mRNA expression by quantitative RT-PCR.

KEY RESULTS:

DNBS administration caused inflammatory damage, increased colonic levels of PEA and endocannabinoids, down-regulation of mRNA for TRPV1 and GPR55 but no changes in mRNA for CB1 , CB2 and PPARα. Exogenous PEA (i.p. and/or p.o., 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 abolished by CB2 receptor, GPR55 or PPARα antagonists and further increased by the TRPV1 antagonist capsazepine.

CONCLUSIONS AND IMPLICATIONS:

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

PMID:
25205418
PMCID:
PMC4280974
DOI:
10.1111/bph.12907
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center