An Update of Palmitoylethanolamide and Luteolin Effects in Preclinical and Clinical Studies of Neuroinflammatory Events

Abstract

The inflammation process represents of a dynamic series of phenomena that manifest themselves with an intense vascular reaction. Neuroinflammation is a reply from the central nervous system (CNS) and the peripheral nervous system (PNS) to a changed homeostasis. There are two cell systems that mediate this process: the glia of the CNS and the lymphocites, monocytes, and macrophages of the hematopoietic system. In both the peripheral and central nervous systems, neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases, and in neuropsychiatric illnesses, such as depression and autism spectrum disorders. The resolution of neuroinflammation is a process that allows for inflamed tissues to return to homeostasis. In this process the important players are represented by lipid mediators. Among the naturally occurring lipid signaling molecules, a prominent role is played by the N-acylethanolamines, namely N-arachidonoylethanolamine and its congener N-palmitoylethanolamine, which is also named palmitoylethanolamide or PEA. PEA possesses a powerful neuroprotective and anti-inflammatory power but has no antioxidant effects per se. For this reason, its co-ultramicronization with the flavonoid luteolin is more efficacious than either molecule alone. Inhibiting or modulating the enzymatic breakdown of PEA represents a complementary therapeutic approach to treating neuroinflammation. The aim of this review is to discuss the role of ultramicronized PEA and co-ultramicronized PEA with luteolin in several neurological diseases using preclinical and clinical approaches.

ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain

“…In this perspective, mast cells provide a potentially important peripheral immune signalling connection to the brain in the inflammatory setting [54]. Mast cells are first responders to intervene as recruiters to initiate, amplify, and prolong all of the immune and nerve responses that arise from their activation [55]. Studies demonstrate that the degranulation of mast cells can produce factors that sensitise nociceptors, thus directly contributing to neuropathic pain [54,56,57].…”

“…[ [61][62][63] Oligondencytes Involved in the formation of myelin, propagation of action potentials along axons, production of neurotrophic factors that support to neurons [55,64]…”

“…In fact, it down-modulates the activation of mast cells and microglia [118]. In addition, multiple studies have demonstrated that the PEA rates are increased in brain regions involving nociception and spinal cord following neuropathic pain induction and other stroke-related conditions [55].…”

“…Furthermore, many studies demonstrated that PEA acts via the direct activation of two different receptors: the nuclear peroxisome proliferator-activated receptor-a (PPAR-α) [121] and the orphan receptor G-protein coupling (GPR55) [122]. In particular, PPAR-α is one of a group of nuclear receptor proteins that function as transcription factors that regulate the expression of genes and it is associated with pro-inflammatory effects [55]. Moreover, in PPAR-α KO mice or mice with blocking PPAR-α antagonists, the anti-inflammatory, anti-nociceptive/anti-neuropathic, and neuroprotective effect of PEA was not detected [123].…”

Synergic Therapeutic Potential of PEA-Um Treatment and NAAA Enzyme Silencing In the Management of Neuroinflammation

“…In neuroinflammatory process the important players are represented by lipid mediators [ 12 ]. Among the naturally occurring lipid signaling molecules, a prominent role is played by NAEs, particularly by PEA, that possesses a powerful neuroprotective and anti-inflammatory power.…”