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PLS-Associated Polyneuropathy Treated with Immunoglobin & Luteolin-Containing Formulation

Posted: Mon 4 Apr 2016 7:44
by RitaA
Unfortunately, there isn't even an abstract (at least not yet) for this article:
J Clin Psychopharmacol. 2016 Apr 1. [Epub ahead of print]

Post-Lyme Syndrome-Associated Polyneuropathy Treated With Immune Immunoglobulin and a Luteolin-Containing Formulation.

Theoharides TC1, Stewart JM.

Author information

1 Molecular Immunopharmacology and Drug Discovery Laboratory Department of Integrative Physiology and Pathobiology Tufts University School of Medicine and Departments of Internal Medicine and Psychiatry Tufts University School of Medicine and Tufts Medical Center Boston, MA

PMID: 27035494 [PubMed - as supplied by publisher]

Re: PLS-Associated Polyneuropathy Treated with Immunoglobin & Luteolin-Containing Formulation

Posted: Mon 4 Apr 2016 7:51
by RitaA
In case anyone else was also wondering, here's a brief description for luteolin: ... 141622.htm
Luteolin stars in study of healthful plant compounds

Date: July 16, 2010

Source: USDA/Agricultural Research Service

Summary: New studies are providing some of the missing details about how natural compounds in plants may protect us against inflammation.


Some of Hwang's on-going studies build upon earlier research in which he and colleagues teased out precise details of how six natural compounds in plants -- luteolin, quercetin, chrysin, eriodicytol, hesperetin, and naringenin -- apparently act as anti-inflammatory agents.

Luteolin is found in celery, thyme, green peppers, and chamomile tea. Foods rich in quercetin include capers, apples, and onions. Chrysin is from the fruit of blue passionflower, a tropical vine. Oranges, grapefruit, lemons, and other citrus fruits are good sources of eriodicytol, hesperetin, and naringenin.

Hwang's team showed, for the first time, that all six plant compounds target an enzyme known as "TBK1." Each compound inhibits, to a greater or lesser extent, TBK1's ability to activate a specific biochemical signal. If unimpeded, the signal would lead to formation of gene products known to trigger inflammation.

Of the six compounds, luteolin was the most effective inhibitor of TBK1. Luteolin is already known to have anti-inflammatory properties. However, Hwang and his colleagues were the first to provide this new, mechanistic explanation of how luteolin exerts its anti-inflammatory effects.

The approaches that the researchers developed to uncover these compounds' effects can be used by scientists elsewhere to identify additional anti-inflammatory compounds present in fruits and vegetables.
I'm not sure how scientific or accurate the following webpage is, however it does list additional sources and benefits of luteolin: ... ector.html

It’s common knowledge that antioxidants reduce inflammation in the body and that inflammation is the cause behind much illness, including many auto-immune diseases. Inflammation in the brain seems to play a major role in age-related memory loss. The University of Illinois study suggests that luteolin acts directly on the immune cells in the brain and spinal cord (known as microglial cells), reducing their production of inflammatory cytokines in the brain, small proteins that affect communication between and behavior of cells. Luteolin’s effect in decreasing the release of these proteins helps protect and, according to lead researcher Rodney Johnson, “allows working memory to be restored to what it was at an earlier stage.” (Journal of Nutrition, October 2010.)

Here is a list of luteolin food sources:

- green bell peppers
- artichokes
- blueberries
- hot green chile peppers
- celery hearts
- thyme
- chamomile tea
- carrots
- olive oil
- peppermint
- rosemary
- parsley
- basil

Re: PLS-Associated Polyneuropathy Treated with Immunoglobin & Luteolin-Containing Formulation

Posted: Mon 4 Apr 2016 8:20
by RitaA
Luteolin has been studied (in mice) since at least 2008, as shown in this article:
Plant flavonoid found to reduce inflammatory response in the brain

May 20, 2008 9:00 am

by Diana Yates

CHAMPAIGN, Ill. - Researchers at the University of Illinois report this week that a plant compound found in abundance in celery and green peppers can disrupt a key component of the inflammatory response in the brain. The findings have implications for research on aging and diseases such as Alzheimer's and multiple sclerosis.


Graduate research assistant Saebyeol Jang studied the inflammatory response in microglial cells. She spurred inflammation by exposing the cells to lipopolysaccharide (LPS), a component of the cell wall of many common bacteria. Those cells that were also exposed to luteolin showed a significantly diminished inflammatory response. Jang showed that luteolin was shutting down production of a key cytokine in the inflammatory pathway, interleukin-6 (IL-6). The effects of luteolin exposure were dramatic, resulting in as much as a 90 percent drop in IL-6 production in the LPS-treated cells.

"This was just about as potent an inhibition as anything we had seen previously," Johnson said.


To see if luteolin might have a similar effect in vivo, the researchers gave mice luteolin-laced drinking water for 21 days before injecting the mice with LPS.

Those mice that were fed luteolin had significantly lower levels of IL-6 in their blood plasma four hours after injection with the LPS. Luteolin also decreased LPS-induced transcription of IL-6 in the hippocampus, a brain region that is critical to spatial learning and memory.

The findings indicate a possible role for luteolin or other bioactive compounds in treating neuroinflammation, Johnson said.

"It might be possible to use flavonoids to inhibit JNK and mitigate inflammatory reactions in the brain," he said. "Inflammatory cytokines such as interleukin-6 are very well known to inhibit certain types of learning and memory that are under the control of the hippocampus, and the hippocampus is also very vulnerable to the insults of aging," he said. "If you had the potential to decrease the production of inflammatory cytokines in the brain you could potentially limit the cognitive deficits that result."

Re: PLS-Associated Polyneuropathy Treated with Immunoglobin & Luteolin-Containing Formulation

Posted: Mon 4 Apr 2016 8:44
by RitaA
Here's a more recent article about luteolin and cognition:
Front Neurosci. 2015 Jul 3;9:225. doi: 10.3389/fnins.2015.00225. eCollection 2015.

Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin.

Theoharides TC1, Stewart JM2, Hatziagelaki E3, Kolaitis G4.

Author information

1 Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine Boston, MA, USA ; Departments of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center Boston, MA, USA ; Psychiatry, Tufts University School of Medicine and Tufts Medical Center Boston, MA, USA ; Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine Boston, MA, USA.
2 Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine Boston, MA, USA.
3 Second Department of Internal Medicine, Attikon General Hospital, Athens Medical School Athens, Greece.
4 Department of Child Psychiatry, University of Athens Medical School, Aghia Sophia Children's Hospital Athens, Greece.


Brain "fog" is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory. Brain "fog" characterizes patients with autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as "minimal cognitive impairment," an early clinical presentation of Alzheimer's disease (AD), and other neuropsychiatric disorders. Brain "fog" may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation. Recent reviews have described the potential use of natural flavonoids for the treatment of neuropsychiatric and neurodegenerative diseases. The flavone luteolin has numerous useful actions that include: anti-oxidant, anti-inflammatory, microglia inhibition, neuroprotection, and memory increase. A liposomal luteolin formulation in olive fruit extract improved attention in children with ASDs and brain "fog" in mastocytosis patients. Methylated luteolin analogs with increased activity and better bioavailability could be developed into effective treatments for neuropsychiatric disorders and brain "fog."


brain; cognition; cytokines; fog; histamine; inflammation; luteolin; mast cells

PMID: 26190965 [PubMed] PMCID: PMC4490655 Free PMC Article
The full article is available here:

Snippets from the full article:
Flavonoids (Figure ​(Figure2)2) are naturally occurring compounds mostly found in green plants and seeds (Middleton et al., 2000). Unfortunately, our modern life diet contains progressively fewer flavonoids and under these conditions, the average person cannot consume enough to make a positive impact on health. Moreover, less than 10% of orally ingested flavonoids are absorbed (Passamonti et al., 2009; Thilakarathna and Rupasinghe, 2013) and are extensively metabolized to inactive ingredients in the liver (Chen et al., 2014).

Luteolin (5,7-3′5′-tetrahydroxyflavone) has potent antioxidant, anti-inflammatory (Middleton et al., 2000) and MC inhibitory activities (Kimata et al., 2000; Kempuraj et al., 2005; Asadi et al., 2010) and also inhibits auto-immune T cell activation (Verbeek et al., 2004; Kempuraj et al., 2008) (Table ​(Table2).2). Luteolin also inhibits microglial IL-6 release (Jang et al., 2008), microglial activation and proliferation (Chen et al., 2008; Dirscherl et al., 2010; Kao et al., 2011), as well as microglia-induced neuron apoptosis (Zhu et al., 2011).
Flavonoids can also inhibit acetylcholinesterase (Tsai et al., 2007; Boudouda et al., 2015), which will increase acetylcholine and improve memory (Table ​(Table1).1). It is of interest that luteolin further inhibits release of the excitatory neurotransmitter glutamate (Lin et al., 2011), while it activates receptors for the inhibitory neurotransmitter γ-amino butyric acid (GABA) independent of GABA, suggesting it may also have a calming effect (Hanrahan et al., 2011). In fact, benzodiazepines that act by activating GABA receptors were shown to bind to MCs (Miller et al., 1988).
Flavonoids are generally considered safe (Kawanishi et al., 2005; Harwood et al., 2007; Seelinger et al., 2008; Corcoran et al., 2012; Theoharides et al., 2014). Unfortunately, some of the cheaper sources of flavonoids found in dietary supplements are from peanut shells and fava beans and may lead to anaphylactic reactions or hemolytic anemia to allergic and G6PD-deficient individuals, respectively. Flavonoids are extensively metabolized (Chen et al., 2014) primarily through glucoronidation, methylation, and sulphation (Hollman et al., 1995; Hollman and Katan, 1997). Therefore, flavonoids must be used with caution when administered with other natural polyphenolic molecules (e.g., curcumin, resveratrol) or drugs metabolized by the liver as they may affect the blood levels of themselves or of other drugs (Theoharides and Asadi, 2012). Tetramethoxyluteolin is already methylated and less likely to affect liver metabolism, is more stable (Walle, 2007), and has better bioavailability (Wei et al., 2014). Intranasal tetramethoxyluteolin preparations would offer the additional advantage of delivering the flavonoid directly to the brain through the cribriform plexus as was shown for some other compounds (Zhuang et al., 2011).

Re: PLS-Associated Polyneuropathy Treated with Immunoglobin & Luteolin-Containing Formulation

Posted: Fri 8 Apr 2016 23:06
by ChronicLyme19
Sounds like luteolin might give a plausible explanation as to the mechanism behind parlsey being prescribed for herxes.