title: Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  PEA improves murine experimental colitis, the effect being mediated by CB2 receptors, GPR55 and PPARα, and modulated by TRPV1 channels.
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Borrelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Romano
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Ester
authors.initials: E
authors.lastname: Pagano
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capasso
authors.forename: Diana
authors.initials: D
authors.lastname: Coppola
authors.forename: Giovanni
authors.initials: G
authors.lastname: Battista
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Orlando
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
mesh_terms: D000284:Administration, Oral; D000577:Amides; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001557:Benzenesulfonates; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000378:metabolism; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008813:Mice, Inbred ICR; D009829:Oleic Acids / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics; D010169:Palmitic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000235:genetics; D043882:Receptors, Cannabinoid / Q000235:genetics; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D001557:Benzenesulfonates; D063388:Endocannabinoids; D004983:Ethanolamines; C526692:GPR55 protein, mouse; D009829:Oleic Acids; C440229:Oleylethanolamide; D047493:PPAR alpha; D010169:Palmitic Acids; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C007488:dinitrobenzenesulfonic acid; C005958:palmidrol; D009195:Peroxidase; C071423:capsazepine; D002211:Capsaicin