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Newly Discovered Plant flavonoid reduces inflammatory response in the brain 5-23-08
University of Illinois at Urbana-Champaign
Animal sciences professor Rodney Johnson, and graduate student Saebyeol Jang
found that a plant flavonoid, luteolin, inhibited a key pathway in the
inflammatory response of microglia.
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.
The study appears this week in Proceedings of the National Academy of Sciences.
Inflammation can be a blessing or a blight. It is a critical part of the body's
immune response that in normal circumstances reduces injury and promotes
healing. When it goes awry, however, the inflammatory response can lead to
serious physical and mental problems.
Inflammation plays a key role in many neurodegenerative diseases and also is
implicated in the cognitive and behavioral impairments seen in aging.
The new study looked at luteolin (LOO-tee-OH-lin), a plant flavonoid known to
impede the inflammatory response in several types of cells outside the central
nervous system. The purpose of the study was to determine if luteolin could also
reduce inflammation in the brain, said animal sciences professor and principal
investigator Rodney Johnson.
"One of the questions we were interested in is whether something like luteolin,
or other bioactive food components, can be used to mitigate age-associated
inflammation and therefore improve cognitive function and avoid some of the
cognitive deficits that occur in aging," Johnson said.
The researchers first studied the effect of luteolin on microglia. These brain
cells are a key component of the immune defense. When infection occurs anywhere
in the body, microglia respond by producing inflammatory cytokines, chemical
messengers that act in the brain to orchestrate a whole-body response that helps
fight the invading microorganism.
This response is associated with many of the most obvious symptoms of illness:
sleepiness, loss of appetite, fever and lethargy, and sometimes a temporary
diminishment of learning and memory. Neuroinflammation can also lead some
neurons to self-destruct, with potentially disastrous consequences if it goes
too far.
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.
But how was luteolin inhibiting production of IL-6?
Jang began by looking at a class of proteins involved in intracellular
signaling, called transcription factors, which bind to specific "promoter"
regions on DNA and increase their transcription into RNA and translation into
proteins.
Using electromobility shift assays, which measure the binding of transcription
factors to DNA promoters, Jang eventually determined that luteolin inhibited
IL-6 production by preventing activator protein-1 (AP-1) from binding the IL-6
promoter.
AP-1 is in turn activated by JNK, an upstream protein kinase. Jang found that
luteolin inhibited JNK phosphorylation in microglial cell culture. The failure
of the JNK to activate the AP-1 transcription factor prevented it from binding
to the promoter region on the IL-6 gene and transcription came to a halt.
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."
Comment:
Fish Oil has also been shown to reduce IL-6 in the body. Make sure it is molecularly distilled. Helichrysum Itallicum essential oil has been shown to reduce neuroinflammation, as well as bio-identical progesterone cream and Evening Primrose oil.