Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent
Authors: Borrelli F., Romano B., Petrosino S., Pagano E., Capasso R., Coppola D., Battista G., Orlando P., Di Marzo V., Izzo AA.
Autors Affiliation: Univ Naples Federico II, Dept Pharm, Via D Montesano 49, I-80131 Naples, Italy; CNR, Inst Biomol Chem, I-80078 Naples, Italy; Osped Pellegrini, Dept Diagnost Serv, Anat & Pathol Histol Service, ASL 1, Naples, Italy; CNR, Inst Prot Biochem, I-80078 Naples, Italy; CNR, Natl Inst Opt, Pozzuoli, Italy
Abstract: Background and PurposePalmitoylethanolamide (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 ) 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 ApproachColitis 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 ResultsDNBS 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 PPAR. Exogenous PEA (i.p. and/or p.o., 1mgkg(-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 PPAR antagonists and further increased by the TRPV1 antagonist capsazepine.
Conclusions and ImplicationsPEA improves murine experimental colitis, the effect being mediated by CB2 receptors, GPR55 and PPAR, and modulated by TRPV1 channels.
Journal/Review: BRITISH JOURNAL OF PHARMACOLOGY
Volume: 172 (1) Pages from: 142 to: 158
KeyWords: INFLAMMATORY-BOWEL-DISEASE; N-PALMITOYL-ETHANOLAMINE; POTENTIAL TRP CHANNELS; CONCISE GUIDE; ENDOCANNABINOID SYSTEM; PPAR-ALPHA; ALTERNATIVE MEDICINE; DRUG TARGETS; FOOD-INTAKE; RECEPTORDOI: 10.1111/bph.12907Citations: 84data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2021-10-17References taken from IsiWeb of Knowledge: (subscribers only)Connecting to view paper tab on IsiWeb: Click hereConnecting to view citations from IsiWeb: Click here