Utilização terapêutica da Palmitoiletanolamida (PEA) como anti-inflamatório e imunomodulador

Abstract

The endocannabinoid system is composed of cannabinoid receptors, naturally occurring endocannabinoid ligands, and enzymes responsible for essential biosynthesis, uptake, and metabolism processes. Among these endogenous cannabinoid ligands are compounds derived from polyunsaturated fatty acids, encompassing long-chain amides, esters, and ethers, with the capacity to bind and activate receptors like anandamide and 2-arachidonoyl-glycerol. Within this category also fall molecules produced through the same pathway, such as Noleoylethanolamine and N-palmitoylethanolamine (PEA). N-palmitoylethanolamine (PEA), a notable member of this category, was first encountered within lipid fractions of specific foods and has intrigued researchers since the 1950s due to its potential therapeutic effects and underlying mechanisms. This study, against this backdrop, aims to comprehensively explore the therapeutic promise held by PEA as a robust antiinflammatory and immunomodulatory agent. PEA's therapeutic impact reverberates across diverse physiological systems, spanning the central nervous system, gastrointestinal tract, vascular network, digestive system, and respiratory pathways. Additionally, its far-reaching influence encompasses effective pain management, curbing inflammatory processes, and finely-tuned modulation of immune responses. These attributes have fostered collaborations targeting conditions such as Alzheimer's disease, multiple sclerosis, cerebral ischemia, neuroinflammation, general inflammation and pain, coagulopathy, steatohepatitis, and acute lung injury. PEA operates both independently and in synergy with other compounds, like paracetamol, luteolin, and oxymetazoline. In scientific investigations, PEA consistently reveals itself as an anti-inflammatory powerhouse, safeguarding neural health, and orchestrating immunomodulation. This efficacy stems from its interactions with pivotal targets including PPARα, PPAR-δ, and PPAR-γ, CB1, CB2, GPR55, and TRPV1. Additionally, PEA exerts a direct influence on the inflammatory cascade, orchestrating precise adjustments in immune responses. Numerous animal studies have elucidated the inherent potential of PEA. This review notably underscores the pivotal necessity for methodologically rigorous clinical trials to definitively establish the translational efficacy of PEA in ameliorating diverse inflammatory pathologies within the human milieu.