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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Tetramethoxyluteolin for the Treatment of Neurodegenerative Diseases

Author(s): Theoharis C. Theoharides* and Irene Tsilioni

Volume 18, Issue 21, 2018

Page: [1872 - 1882] Pages: 11

DOI: 10.2174/1568026617666181119154247

Price: $65

Abstract

Background: Most neurodegenerative and other brain disorders, especially Myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) and autism spectrum disorder (ASD) continue to elude objective biomarkers and effective treatments. Increasing evidence indicates that such diseases involve focal inflammation of the brain.

Objective: To review the role of cytokine-neuropeptide interactions in the pathogenesis of inflammation of the brain and the beneficial role of natural flavonoids.

Methods: Medline search was conducted (2000-2017) for articles using the terms allergy, amygdala, atopy, autism, brain, chemokines, cytokines, hypothalamus, immunity, inflammation, mast cells, microglia, neurotensin, peptides, substance P, and TNF.

Results: Neuropeptides and cytokine stimulation of mast cells and microglia can result in focal inflammation in the hypothalamus and amygdala, thus explaining most of the symptoms at least in ME/CFS and ASD. Some of the triggers may be corticotropin-releasing hormone (CRH), neurotensin (NT), and substance P (SP), which have synergistic action on IL-33. The natural flavonoids luteolin and tetramethoxyluteolin inhibit these processes and have neuroprotective actions. Tetramethoxyluteolin is also more metabolically stable and has greater oral absorption.

Conclusion: Inhibition of inflammatory processes unique to the brain with intranasal formulations of tetramethoxyluteolin could provide new possibilities for the understanding and treatment of neurodegenerative diseases.

Keywords: Autism spectrum disorder, Cytokines, Inflammation, Mast cells, Microglia, Myalgic encephalomyelitis/chronic fatigue syndrome, Luteolin, Tetramethoxyluteolin.

Graphical Abstract

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