An Update of Palmitoylethanolamide and Luteolin Effects in Preclinical and Clinical Studies of Neuroinflammatory Events
Open accessAbstract
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)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Cordaro et al., 2020
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Piccialli, I., Tedeschi, V., Caputo, L., D’Errico, S., Ciccone, R., De Feo, V., Secondo, A., & Pannaccione, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.876614 · Cited by 73 · see citing works
He, M.-C., Shi, Z., Sha, N.-N., Chen, N., Peng, S.-Y., Liao, D.-F., Wong, M.-S., Dong, X.-L., Wang, Y.-J., Yuan, T.-F., et al. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.01.021 · Cited by 54 · see citing works
- 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)
- PMC
- PMC7139331
- 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
- gold
- dx.doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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