2-pentadecyl-2-oxazoline: Identification in coffee, synthesis and activity in a rat model of carrageenan-induced hindpaw inflammation. (June 2016)

• Record Type: Journal Article
• Authors: Impellizzeri, Daniela; Cordaro, Marika; Bruschetta, Giuseppe; Crupi, Rosalia; Pascali, Jennifer; Alfonsi, Daniele; Marcolongo, Gabriele; Cuzzocrea, Salvatore
• Is Part Of: Pharmacological research. Volume 108(2016:Jun.)
• Page Start: 23
• Page End: 30
• Publication Date: 2016-06
• Subjects: CAR carrageenan -- NAAAN -acylethanolamine-hydrolysing acid amidase -- NAE N-acylethanolamines -- PEA N-palmitoylethanolamine -- PEA-OXA pentadecyl-2-oxazoline; Analgesic -- Cannabinoids -- Chemical synthesis -- Endocannabinoid -- Fatty acid -- N-acylethanolamine -- N-palmitoylethanolamine -- Neuroinflammation; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2016.04.007
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: 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 6 h 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 (10 mg/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.