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Tetramethoxyluteolin for the treatment of neurodegenerative diseases.

Murph

:)
Messages
1,799
Curr Top Med Chem. 2018 Nov 19. doi: 10.2174/1568026617666181119154247. [Epub ahead of print]
Tetramethoxyluteolin for the treatment of neurodegenerative diseases.
Theoharides TC1, Tsilioni I1.
Author information
1
Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Immunology, Tufts University School of Medicine, Boston, MA. United States.
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.

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 leass 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.

KEYWORDS:
Autism spectrum disorder; cytokines; inflammation; luteolin; mast cells; microglia; myalgic encephalomyelitis/chronic fatigue syndrome; tetramethoxyluteolin; tetramethoxyluteolinAutism spectrum disorder

PMID:
30451113
DOI:
10.2174/1568026617666181119154247
 

Murph

:)
Messages
1,799
This stuff can inhibit mast cells

https://www.jacionline.org/article/S0091-6749(14)01574-7/abstract

Background
Mast cells (MCs) are hematopoietic cells that mature in tissues and are involved in allergy, immunity, and inflammation by secreting multiple mediators. The natural flavone luteolin has anti-inflammatory actions and inhibits human mast cells (MCs).

Objective
We sought to investigate the ability of luteolin and its novel structural analog 3′,4′,5,7-tetramethoxyluteolin (methlut) to inhibit human MC mediator expression and release in vitro and in vivo.

Methods
Human LAD2 cells and umbilical primary human cord blood–derived cultured mast cells were stimulated with substance P (SP) or IgE/anti-IgE with or without preincubation with luteolin, methlut, or cromolyn (1-100 μmol/L) for 2 or 24 hours, after which mediator secretion was measured. The effect of the compounds on MC intracellular calcium levels and nuclear factor κB activation was also investigated. Pretreatment with methlut was also studied in mice passively sensitized with dinitrophenol–human serum albumin and challenged intradermally.

Results
Methlut is a more potent inhibitor than luteolin or cromolyn for β-hexosaminidase and histamine secretion from LAD2 cells stimulated by either SP or IgE/anti-IgE, but only methlut and luteolin significantly inhibit preformed TNF secretion. Methlut is also a more potent inhibitor than luteolin of de novo–synthesized TNF from LAD2 cells and of CCL2 from human cord blood–derived cultured MCs. This mechanism of action for methlut might be due to its ability to inhibit intracellular calcium level increases, as well as nuclear factor κB induction, at both the transcriptional and translational levels in LAD2 cells stimulated by SP without affecting cell viability. Intraperitoneal treatment with methlut significantly decreases skin vascular permeability of Evans blue dye in mice passively sensitized to dinitrophenol–human serum albumin and challenged intradermally.

Conclusion
Methlut is a promising MC inhibitor for the treatment of allergic and inflammatory conditions.

You can rub it on yourself as a lotion, apparently: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806797/ (Some cool pictures in here of people who had skin lesions getting them cleared up by the lotion.
 

Hip

Senior Member
Messages
17,824
I've tried regular luteolin 100 mg daily (not be confused with the antioxidant lutein) for my ME/CFS, without noticing much benefit (but I do not have MCAS). Tetramethoxyluteolin appears to be a more potent version of luteolin.
 
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Location
The Netherlands
Last edited:

Marylib

Senior Member
Messages
1,155
Sounds like a good plan. Has anyone put him in communication with Robert Naviaux..like perhaps @Rachel Riggs? Naviaux is the only guy who seems to be interested in both ME and Autism. Mast cells and peptides are a hot topic.