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; Luteolin; Mast cells; Microglia; Myalgic encephalomyelitis/chronic fatigue syndrome; Tetramethoxyluteolin..
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