ME/CFS is a mast cell disorder (hypothesis)

Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype.

http://www.ncbi.nlm.nih.gov/pubmed/20074346
Abstract

BACKGROUND:

Luteolin, a plant derived flavonoid, exerts a variety of pharmacological activities and anti-oxidant properties associated with its capacity to scavenge oxygen and nitrogen species. Luteolin also shows potent anti-inflammatory activities by inhibiting nuclear factor kappa B (NFkB) signaling in immune cells. To better understand the immuno-modulatory effects of this important flavonoid, we performed a genome-wide expression analysis in pro-inflammatory challenged microglia treated with luteolin and conducted a phenotypic and functional characterization.
METHODS:

Resting and LPS-activated BV-2 microglia were treated with luteolin in various concentrations and mRNA levels of pro-inflammatory markers were determined. DNA microarray experiments and bioinformatic data mining were performed to capture global transcriptomic changes following luteolin stimulation of microglia. Extensive qRT-PCR analyses were carried out for an independent confirmation of newly identified luteolin-regulated transcripts. The activation state of luteolin-treated microglia was assessed by morphological characterization. Microglia-mediated neurotoxicity was assessed by quantifying secreted nitric oxide levels and apoptosis of 661W photoreceptors cultured in microglia-conditioned medium.
RESULTS:

Luteolin dose-dependently suppressed pro-inflammatory marker expression in LPS-activated microglia and triggered global changes in the microglial transcriptome with more than 50 differentially expressed transcripts. Pro-inflammatory and pro-apoptotic gene expression was effectively blocked by luteolin. In contrast, mRNA levels of genes related to anti-oxidant metabolism, phagocytic uptake, ramification, and chemotaxis were significantly induced. Luteolin treatment had a major effect on microglial morphology leading to ramification of formerly amoeboid cells associated with the formation of long filopodia. When co-incubated with luteolin, LPS-activated microglia showed strongly reduced NO secretion and significantly decreased neurotoxicity on 661W photoreceptor cultures.
CONCLUSIONS:

Our findings confirm the inhibitory effects of luteolin on pro-inflammatory cytokine expression in microglia. Moreover, our transcriptomic data suggest that this flavonoid is a potent modulator of microglial activation and affects several signaling pathways leading to a unique phenotype with anti-inflammatory, anti-oxidative, and neuroprotective characteristics. With the identification of several novel luteolin-regulated genes, our findings provide a molecular basis to understand the versatile effects of luteolin on microglial homeostasis. The data also suggest that luteolin could be a promising candidate to develop immuno-modulatory and neuroprotective therapies for the treatment of neurodegenerative disorders.


Products to try: NeuroProtek or LutiMax. I started NeuroProtek today but also ordered LutiMax for comparison purposes.

There's also luteolin in the LEF butterbur/rosmarinic acid product.

Only 4mg per cap, though. Each NeuroProtek or Lutimax capsule has 100mg per cap!

I am curious, what dosage were you on? By the way, I expect NeuroProtek to be superior to LutiMax due to the patented liposomal delivery formulation used.

Yeah, Neuroprotek look interesting. Unfortunately, whenever I've tried quercetin I have developed hives, and felt downright miserable. Don't know what that is about.

Did you try it with or without food?

Based on NeuroProtek recommendations, I am going for 900mg of luteolin a day, in three dosages. I also like to take this stuff on an empty stomach.

How much quercetin did you try? Algonot also has a so-called low phenol version (NeuroProtek LP) with only 40mg of quercetin and 1mg of rutin.

Ok, thanks for the heads up. Seems terribly expensive though, at 9 caps a day. I'll wait for your report

Any idea exactly what cytokines is touching? I have my pro inflammatory: some ok some high so I guess you would need to understand exactly what is doing so you don't make your individual case worse?? And When I saw the data how you translate that to ILs? (I have high IL1b,TNFR I and II low)

Article: Luteolin Reduces Lipopolysaccharide-induced Lethal Toxicity and Expression of Proinflammatory Molecules in Mice

Assuming this translates to humans, it should help those with translocation of bacterial lipopolysaccharides from the gut.

Since many of us have MCS as an add-on to M.E., I thought this article might be of interest. Apparently there is a mast cell connection in some cases here too. The Role of the Brain and Mast Cells in MCS

I have been taking NeuroProtek for almost a month now, with an interruption of a couple of days while waiting for a shipment. For me, this stuff works! Those two days without NeuroProtek were absolutely terrible, with extreme fatigue and terrible brain fog. Once I restarted the NeuroProtek, things returned to "normal". I am not cured but life is much more bearable now. I take the maximum recommended dosage of 9 caps/day, three caps one hour before each of the three meals.

Same here. Tried LutiMax for a couple of days while waiting for additional NeuroProtek. Unlike NeuroProtek, LutiMax did nothing for me.

What other symptoms would NeuroProtek be expected to work on? Might it help with things like hypersensitivity to odours, light, foods etc. or migraines?

What is the difference between the regular and LP (low phenol) versions of NeuroProtek? There is no phenol in the ingredient list, so does something produce phenol in the body?

I have found a small benefit from quercetin in the past. I have not tried any Luteolin products though. Bye, Alex

Phenolic compounds are extremely common in plants. Low phenol should also mean low in compounds that break down to phenols. Bye, Alex

According to Theoharides, the rutin in NeuroProtek is directed at the gut, to help with intestinal hyperpermeability, and luteolin is directed at the brain to deal with neurological symptoms. The quercetin is there as a decoy to keep the liver "busy" and prevent degradation of luteolin.

Honestly, I don't know. I suspect it would help with migraines at least but this is just a guess.

The LP version has less quercetin and rutin for people that are sensitive to them. Additional info here: Algonot NeuroProtek FAQ.

There is also a video where Theoharides explains some of the stuff NeuroProtek does: