Adelmidrol, a palmitoylethanolamide analogue, as a new pharmacological treatment for the management of acute and chronic inflammation

作者：Impellizzeri Daniela; Di Paola Rosanna; Cordaro Marika; Gugliandolo Enrico; Casili Giovanna; Morittu Valeria Maria; Britti Domenico; Esposito Emanuela; Cuzzocrea Salvatore^*

来源：Biochemical Pharmacology, 2016, 119: 27-41.

DOI：10.1016/j.bcp.2016.09.001

• Adelmidrol
• ALIAmides
• Cytokines
• Inflammation
• Mast cells
• PPARS

The aim of study was to examine the anti-inflammatory and analgesic effects of adelmidrol, an analogue of palmitoylethanolamide (PEA), in animal models of acute and chronic inflammation [carrageenan-induced paw edema (CAR) and collagen-induced arthritis (CIA)].
In order to elucidate whether the action of adelmidrol is related to activation of peroxisome proliferator-activated receptors (PPAR-alpha or PPAR-gamma), we investigated the effects of PPAR-gamma antagonist, GW9662 on adelmidrol mechanism. CAR induced paw edema, hyperalgesia and the activation of pro inflammatory NF-kappa B pathway were markedly reduced by treatment with adelmidrol. GW9662, (administered prior to adelmidrol treatment), antagonized the effect of adelmidrol abolishing its positive action. On the contrary, the genetic absence of PPAR-alpha receptor did not modify the beneficial results of adelmidrol treatment in the acute model of inflammation.
In addition, for the first time, we demonstrated that adelmidrol was able to ameliorate both the clinical signs and the histopathology of the joint and the hind paw during chronic inflammation. In particular, the degree of oxidative damage and proinflammatory cytokines and chemokines production were significantly reduced in adelmidrol-treated mice. Moreover, in CIA model, the effect of GW9662 pretreatment on adelmidrol mechanism was also confirmed. Thus, in this study, we report that adelmidrol reduces the development of acute and chronic inflammation and could represent a novel therapeutic approach for inflammation and pain.

• 出版日期2016-11-1