Department of Biological and Environmental Sciences, Viale Ferdinando Stagno D'Alcontres, 31, 98166, University of Messina, Messina, Italy.
Mini Rev Med Chem. 2013 Feb;13(2):237-55.
The endogenous fatty acid palmitoylethanolamide (PEA) is one of the members of N-acyl-ethanolamines family. PEA was identified more than five decades ago and was shown to reduce allergic reactions and inflammation in animals along with influenza symptoms in humans. Interest in this compound faded, however, until the discovery that one of its structural analogs, anandamide (arachidonoylethanolamide), serves as an endogenous ligand for cannabinoid receptors, the molecular target of Δ9-tetrahydrocannabinol in marijuana. Since this finding, PEA has been shown to inhibit peripheral inflammation and mast-cell degranulation, as well as to exert neuroprotective and antinociceptive effects in rats and mice. These actions are also mediated by PPAR-α activation and are accompanied by a decrease in nitric oxide production, neutrophil influx, and expression of proinflammatory proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition to the hypothesis that PEA has potent immunoregulatory properties, recent data have demonstrated that PEA may also play a key role in the regulation of complex systems involved in the inflammatory response, pruritus, neurogenic and neuropathic pain. In this review, we discuss briefly the present understanding therapeutic mechanisms of PEA and the novel possible PEA clinical use for the treatment of several inflammatory diseases and trauma.
内源性脂肪酸乙醇酰胺（PEA）是 N-酰基乙醇胺家族的成员之一。PEA 早在五十年前就被发现，在动物中可减少过敏反应和炎症，以及减轻人类流感症状。然而，人们对这种化合物的兴趣逐渐减退，直到发现其结构类似物之一——花生四烯酸乙醇酰胺（arachidonoylethanolamide），作为大麻素受体的内源性配体，大麻中 Δ9-四氢大麻酚的分子靶标。自这一发现以来，PEA 已被证明可抑制外周炎症和肥大细胞脱颗粒，以及在大鼠和小鼠中发挥神经保护和镇痛作用。这些作用也通过 PPAR-α 激活介导，并伴随着一氧化氮产生、中性粒细胞浸润和促炎蛋白（如诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2））表达的减少。除了 PEA 具有强大的免疫调节特性的假设外，最近的数据还表明，PEA 可能在调节涉及炎症反应、瘙痒、神经源性和神经性疼痛的复杂系统中也发挥关键作用。在这篇综述中，我们简要讨论了 PEA 的治疗机制以及 PEA 在治疗几种炎症性疾病和创伤方面的新的可能临床应用。
