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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amides
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Benzenesulfonates
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / pathology
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Disease Models, Animal
  • Endocannabinoids / metabolism
  • Ethanolamines / administration & dosage
  • Ethanolamines / pharmacokinetics
  • Ethanolamines / pharmacology
  • Ethanolamines / therapeutic use*
  • Intestinal Absorption / drug effects
  • Male
  • Mice, Inbred ICR
  • Oleic Acids / metabolism
  • PPAR alpha / genetics
  • Palmitic Acids / administration & dosage
  • Palmitic Acids / pharmacokinetics
  • Palmitic Acids / pharmacology
  • Palmitic Acids / therapeutic use*
  • Peroxidase / metabolism
  • RNA, Messenger / metabolism
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / genetics
  • Receptors, Cannabinoid / genetics
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / genetics

Substances

  • Amides
  • Anti-Inflammatory Agents
  • Benzenesulfonates
  • Endocannabinoids
  • Ethanolamines
  • GPR55 protein, mouse
  • Oleic Acids
  • Oleylethanolamide
  • PPAR alpha
  • Palmitic Acids
  • RNA, Messenger
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Receptors, Cannabinoid
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • dinitrobenzenesulfonic acid
  • palmidrol
  • Peroxidase
  • capsazepine
  • Capsaicin