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.
Current Topics in Medicinal Chemistry
Title:Tetramethoxyluteolin for the Treatment of Neurodegenerative Diseases
Volume: 18 Issue: 21
Author(s): Theoharis C. Theoharides*Irene Tsilioni
Affiliation:
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Immunology, Tufts University School of Medicine, Boston, MA,United States
Keywords: Autism spectrum disorder, Cytokines, Inflammation, Mast cells, Microglia, Myalgic encephalomyelitis/chronic fatigue syndrome, Luteolin, Tetramethoxyluteolin.
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.
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Cite this article as:
Theoharides C. Theoharis*, Tsilioni Irene, Tetramethoxyluteolin for the Treatment of Neurodegenerative Diseases, Current Topics in Medicinal Chemistry 2018; 18 (21) . https://dx.doi.org/10.2174/1568026617666181119154247
DOI https://dx.doi.org/10.2174/1568026617666181119154247 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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