title: 2-pentadecyl-2-oxazoline: Identification in coffee, synthesis and activity in a rat model of carrageenan-induced hindpaw inflammation.
abstract: N-acylethanolamines (NAEs) comprise a family of bioactive lipid molecules present in animal and plant tissues, with N-palmitoylethanolamine (PEA) having received much attention owing to its anti-inflammatory, analgesic and neuroprotective activities. 2-Pentadecyl-2-oxazoline (PEA-OXA), the oxazoline of PEA, reportedly modulates activity of N-acylethanolamine-hydrolyzing acid amidase (NAAA), which catabolizes PEA. Because PEA is produced on demand and exerts pleiotropic effects on non-neuronal cells implicated in neuroinflammation, modulating the specific amidases for NAEs (NAAA in particular) could be a way to preserve PEA role in maintaining cellular homeostasis through its rapid on-demand synthesis and equally rapid degradation. This study provides the first description of PEA-OXA in both green and roasted coffee beans and Moka infusions, and its synthesis. In an established model of carrageenan (CAR)-induced rat paw inflammation, PEA-OXA was orally active in limiting histological damage and thermal hyperalgesia 6h after CAR intraplantar injection in the right hindpaw and the accumulation of infiltrating inflammatory cells. PEA-OXA appeared to be more potent compared to ultramicronized PEA given orally at the same dose (10mg/kg). PEA-OXA markedly reduced also the increase in hindpaw myeloperoxidase activity, an index of polymorphonuclear cell accumulation in inflammatory tissues. NAAA modulators like PEA-OXA may serve to maximize availability of NAEs (e.g. PEA) while providing for recycling of the NAE components for further resynthesis.
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bruschetta
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Crupi
authors.affiliation: dto Labs Analytical Excellence Center, Agilent Technologies, Via Fratta 25, 31023, Resana (TV), Italy.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pascali
authors.affiliation: Epitech Spa, Via Einaudi 13, 35030, Saccolongo (PD), Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Alfonsi
authors.affiliation: Epitech Spa, Via Einaudi 13, 35030, Saccolongo (PD), Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Marcolongo
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. Electronic address: salvator@unime.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D002351:Carrageenan; D003069:Coffee / Q000737:chemistry; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D009195:Peroxidase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C000625920:2-pentadecyl-2-oxazoline; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D003069:Coffee; D010080:Oxazoles; D002351:Carrageenan; D009195:Peroxidase
keywords: Analgesic; Cannabinoids; Chemical synthesis; Endocannabinoid; Fatty acid; N-acylethanolamine; N-palmitoylethanolamine; Neuroinflammation