I was reading some interesting things on another DS forum about possible benefits of flavonoids in lung disease that inspired a little further research into the bioflavonoids quercetin, apigenin, and luteolin.

It's a bit of a strange story - one researcher seems to be making extravagant claims about traditional medicines containing some of these substances "curing" COPD, and on the other hand the same researcher has participated in what looks like respectable research that may be independently supported by other work, that at least makes it sounds like these things could be of benefit to people with lung trouble by decreasing mucus production that's promoted by inflammation.

https://www.dailystrength.org/group/asthma/discussion/how-to-prevent-the-recurrence-of-asthma

I used to take quercetin before I developed such lung troubles just because it's supposed to be "good for you" and an antioxidant, but gave up since I never felt like it was doing anything for me. I'd heard it was an antihistamine, and I'd heard that it could inhibit certain allergens by binding to them and changing their shape so they are no longer allergens, but more recently I'm hearing quercetin and other "bioflavonoids" described as mast cell inhibitors.

Paolo Maccallini's site raises the possibility of mast cell abnormalities in CFS

Mast Cells and Post-Exertional Malaise by Paolo Maccallini
https://paolomaccallini.com/2016/06/02/fatica-post-sforzo-e-mastociti
"Background
There is a rare disease in which mast cells degranulation is induced by an exercise of low intensity, particularly by exercises that require whole body involvement, such as jogging, aerobics and walking (Barg W et al. 2011). The name of this disease is exercise-induced anaphylaxis (EIA). There is another recently defined disorder due to abnormal activity of mast cells, the name of which is mast cell activation syndrome (MCAS), that has been linked to fatigue, brain fog, and orthostatic intolerance (Akin L, 2010).
The hypothesis
MCAS has already been somehow associated to ME/CFS by various Authors (Afrin L et al. 2016) however, to my knowledge, nobody has suggested that the possible link between CFS and MCAS may be an exercise-induced increased release of mediators by mast cells. In other words, post-exertional malaise (PEM) could be – according to this hypothesis – a form of exercise-induced mast cell activation similar to EIA, but without anaphylaxis. A possible reason for exercise-induced mediators release could be found in the abnormally high level of C4a, six hours after exercise in CFS (Sorensen, 2003). C4a – along with C4b – is the split product of C4, a protein of the complement system. As C4a is also an anaphylatoxin (i.e. a protein which stimulates mast cells) it could be a trigger for exercise-induced activation. One of the feasible mechanisms for mast cells induced fatigue is the following one: release of fragmented mitochondria by activated mast cells (Zhang et al. 2012) may be a trigger for the cell danger response (CDR) through activation of the purinergic system, with consequent shut down of mitochondria (Naviaux R, 2013)."

I'm gratified he's mentioned the puringeric system and Naviaux at the end of these excerpts - adenosine produced by infection may be able to activate the puringeric system, and in this context perhaps it might help explain how adenosine is supposed to be able to trigger asthma attacks when inhaled (i.e., via mast cell activation?). (I've had some things to say about adenosine and CFS in my tread about the "Metabolic Trap"). Perhaps it might not take anything quite as drastic as mitochrondial fragmentation to set off a cell danger response if adenosine will suffice, although it may not be the only possible trigger?

(Paolo's page mentions a number of mast cell activators which include the inflammatory factors IL-6 and TNF-a).

Paolo also goes on to say,

"Mast cells and Lyme disease
It has been demonstrated in vitro the potential for mast cells activation by B. burgdorferi spirochetes, with a consequent TNF-a release (Talkington et al. 1999). Thus, a possible link between mast cells mediators and currently unexplained symptoms of Lyme disease and – more importantly – of post-treatment Lyme disease syndrome (PTLDS), should be investigated."

TNF-a release is one of the things that substances like some of these flavonoids is supposed to inhibit.

This seems to raise the question whether quercetin might be of benefit to CFS patients, and whether quercetin and some of these other flavonoids might be relatively safe things to try at least as far as toxicity goes.

I've been trying some of them myself with possible good but mixed results - luteolin seems to aggravate my skin condition, and it seems challenging to gauge the success of things for lung trouble that may be subject to various triggers. Still, I've had sporadic bouts of feeling much better and being able to do things I usually cannot do, and wonder if the different flavonoids I've started to try may have played a role in that.

Way too soon for me to recommend these to anyone obviously, but I'm curious whether others have any experience with them.

This article has some interesting research and gives a number of additional references that sound like they might be promising

Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators - relevance to chronic fatigue syndrome
Magdalini Vasiadi, Jennifer Newman, and Theoharis C Theoharides
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236420
"Quercetin increases exercise tolerance in mice [91]. Oral administration of quercetin leads to accumulation in brain tissue and attenuates the increased oxidative stress in the hippocampus and striatum of rats exposed to chronic forced swimming [92,93]. Quercetin has potent anti-oxidant and anti-inflammatory activity [41,42], and inhibits MC degranulation [94,95], as well as TNF-a, IL-6, and IL-8 secretion [95,96]. Moreover, it reverses acute stress-induced behavioral changes and reduces brain glutathione levels in mice [97].

Recent studies with antigen-stimulated MC show that epigallocatechin gallate (EGCG) inhibits MC degranulation, leukotriene C4 secretion, as well as the production of TNF-a, IL-6 and IL-8 [94,96]. The quercetin-related flavone luteolin inhibits MC activation [98] and MC-dependent stimulation of activated T cells [51]. Luteolin also inhibits IL-6 release from microglia cells [99] and from astrocytes [100]. Recent reviews have addressed the possible use of flavonoids for the treatment of CNS diseases [101,102]."

This is some old news from the DS group Lungs & Respiration / Asthma Support Group
Mast cell treatment study
https://www.dailystrength.org/group/asthma/discussion/mast-cell-treatment-study

I don't know if there are drawbacks or cautions to trying flavonoids with these kinds of anti-inflammatory properties, although perhaps it might be noted that lowering TNF-a is also a property of the medication Humira (Humira is an antibody to TNF-a, which neutralizes it).. Humira carries warnings about increasing the risks of certain infections, or even avoiding Humira if you already have an infection.

On the other hand, Humira may be seeing use in a lot of conditions that could have infection as an underlying cause (as suggested by research), which their doctors may be unaware of. (Hidradenitis suppurativa may be a good example of just such a disease).

So I am not sure what to think of all this, just wondering if there are some possibilities here?

Let me have a closer look here at my guess that adenosine may trigger asthma attacks by causing mast cell degranulation (although I think these particular articles may refer to lung mast cells specifically?)

Adenosine-mediated mast cell degranulation in adenosine deaminase-deficient mice.
Zhong H1, Chunn JL, Volmer JB, Fozard JR, Blackburn MR.
https://www.ncbi.nlm.nih.gov/pubmed/11454903
"Adenosine is a signaling nucleoside that has been suggested to play a role in asthma in part through its ability to influence mediator release from mast cells. Adenosine levels are elevated in the lungs of asthmatics, further implicating this molecule in the regulation of lung inflammation and suggesting that animal models exhibiting endogenous increases in adenosine will be useful for the analysis of adenosine function...
treatment of ADA-deficient mice with broad spectrum adenosine receptor antagonists attenuated degranulation by 30 to 40%, supporting the involvement of adenosine receptor signaling. Moreover, these studies demonstrate the ability of endogenously generated adenosine to influence lung mast cell degranulation in a receptor-mediated manner and establish ADA-deficient mice as a model system to investigate the specific adenosine receptor responses involved in the degranulation of lung mast cells."

The A3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells.
Ramkumar V1, Stiles GL, Beaven MA, Ali H.
https://www.ncbi.nlm.nih.gov/pubmed/8349579
"Mast cells release the mediators of the immediate hypersensitivity reaction. Adenosine is known to modulate this process...
while activation of these receptors alone produced little secretory response in RBL-2H3 cells, it enhanced antigen-induced secretion by 2-2.5-fold...
These data indicate that the unique AR that potentiates the secretory response to antigen in RBL-2H3 cells is exclusively the A3AR."

Purinergic Signaling in Mast Cell Degranulation and Asthma.
Gao ZG1, Jacobson KA1.
https://www.ncbi.nlm.nih.gov/pubmed/29311944
"Mast cells are responsible for the majority of allergic conditions...
These mediators are responsible for the symptoms in allergic conditions such as allergic asthma. In recent years, it has been realized that purinergic signaling, induced via the activation of G protein-coupled adenosine receptors and P2Y nucleotide receptors, as well as by ATP-gated P2X receptors, plays a significant role in mast cell degranulation. Both adenosine and ATP can induce degranulation and bronchoconstriction on their own and synergistically with allergens."

There seem to be many more works on the general subject but I'll leave it at that.