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.
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Method: 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, TNF.
Results: Neuropeptides and cytokine stimulation of mast cells and microglia can results 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 has synergistic action with 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.
Source: Theoharides TC, Tsilioni I. Tetramethoxyluteolin for the treatment of neurodegenerative diseases. Curr Top Med Chem. 2018 Nov 19. doi: 10.2174/1568026617666181119154247. [Epub ahead of print]