Cited by 98Fatty Acid Research and HealthNeuroinflammation and Neurodegeneration MechanismsPain Mechanisms and Treatments

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

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Cordaro, Marika, Cuzzocrea, Salvatore, Crupi, Rosalia·2020·Antioxidants

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.

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  • Luteolin improves cognitive abilities in a mouse model of vascular dementia by modulating pro-inflammatory and pro-apoptotic proteins and stimulating neurogenesis.

    “luteolin has been demonstrated to improve cognitive abilities in a mouse model of vascular dementia by modulating the expression of pro-inflammatory and pro-apoptotic proteins and by stimulating neurogenesis (Siracusa et al., 2017; Cordaro et al., 2020)”

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  1. [150]Cotran R.S. Kumar V. Collins T. Robbins S.L. Robbins Pathologic Basis of Disease WB Saunders CompHny Philadelphia, PA, USA 2004
  2. [237]Dirscherl K. Karlstetter M. Ebert S. Kraus D. Hlawatsch J. Walczak Y. Moehle C. Fuchshofer R. Langmann T. Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype (vol 7, pg 3, 2010) J. Neuroinflamm. 2012 9 10.1186/1742-2094-9-118 PMC2819254 20074346 · DOI

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Authors
Cordaro, M., Cuzzocrea, S., & Crupi, R.
Affiliations
University of Messina (IT)
Corresponding author
Cuzzocrea, Salvatore
Venue
Antioxidants
Publisher
MDPI AG
Published
2020-03-05
Volume
9
Issue
3
Pages
216
ISSN
2076-3921 (ISSN-L)
OpenAlex
W3010300386
Cited by
98
References
257
Citations by year
2026: 9 · 2025: 12 · 2024: 17 · 2023: 9 · 2022: 19 · 2021: 12 · 2020: 14 · 2019: 4 · 2018: 1
FWCI
1.66
Type
journal article
Language
en
Open access
Locations
  • Antioxidants (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
palmitoylethanolamide, luteolin, neuroinflammation, N-acylethanolamines, N-arachidonoyl ethanolamide, neuroprotection, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, depression, autism spectrum disorder, lipid mediators, anti-inflammatory activity, flavonoids

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