www.perpetualcommotion.com
"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
- Myricetin -
General Information:
Names: Myricetin, Cannabiscetin,
Myricetol, Myricitin
Wikipedia entry: http://en.wikipedia.org/wiki/Myricetin
Dr. Ray Shahelien entry: http://www.raysahelian.com/myricetin.html
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Observations:
...Quercetin and structurally related flavonoids (myricetin, fisetin, luteolin)...
This flavonoid,an extract of the
Chinese bayberry (Myrica rubra) plant, is under intense study in
several universities. Dr. Chad Dickey and his team patented their
formulation in 2010, anticipating a breakthrough treatment for
tauopathies using this.
http://www.sumobrain.com/patents/wipo/Materials-methods-reduction-proteintau/WO2012012798A2.pdf
Began mid-May, 2012.
One person diagnosed with CBD has found good results using
Myricetin 100 mg tabs, two at bedtime and two in a.m.
Reports profound improvement in speech after taking myricetin
about 10 days. Apraxia improved but improvements are subtle.
"Myricetin is being studied in several university labs because it
is both low toxicity and reduces intracellular tau levels in a
different way compared to curcumin, fisetin , and trehalose--to
the extent that world-class tau researcher Dr. Chad Dickey's group
has patented one formulation of this extract of the Bayberry
plant... In my experience, the Longvida curcumin and the myricetin
are the most powerful elements of this complementary regimen..."
http://www.sumobrain.com/patents/wipo/Materials-methods-reduction-protein-tau/WO2012012798A2.pdf
lecithin/quercetin preparation
http://www.mobilereagents.com/ gives blood-brain barrier info for chemicals
PMID: 15611092 Myricetin is actually better than MB for inhibiting tau filament formation (IC50s of 1.2 and 1.9 microM).
USDA Database for the Flavonoid
Content of Selected Foods
http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/flav.pdf
http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/Flav02-1.pdf
http://lpi.oregonstate.edu/infocenter/phytochemicals/flavonoids/
Flavonoid Content of Vegetables
http://www.nal.usda.gov/fnic/foodcomp/Data/Other/AICR03_VegFl
Myricetin and Neurodegnerative:
Myricetin and brai health [Myricetin and brain health]
Excitotoxicity is the pathological process by which nerve cells
are damaged by glutamate, when receptors for the excitatory
neurotransmitter glutamate, such as the NMDA receptor, are
overactivated. Excitotoxins, high levels of glutamate, reactive
oxygen species generation or caspase-3 activation can cause
excitotoxicity by allowing high levels of calcium ions to enter
the cell. The high level of calcium in the cells activates a
enzymes that can damage cell structures, resulting in diseases
such as Alzheimer. A study conducted by Y Shimmyo and coworkers at
Kyoto University showed that myricetin was a potent
anti-neurodegenerative compound and may contribute to the
discovery of a drug against neurodegeneration [1]. The scientists
came to that conclusion after investigating the effect of
myricetin on neurons. They found that myricetin reduced the
excitotoxicity by different pathways. Myricetin modulated the NMDA
receptor by phosphorylation, resulting in a reduced intracellular
calcium level. Myricetin also inhibited ROS production caused by
glutamate and reduced glutamate-induced activation of caspase-3.
A study by the Qingdao University, China, concluded that myricetin
had protective effect on the toxicity of neurotoxin
6-hydroxydopamine by suppressing iron toxicity [2]. The main use
of 6-hydroxydopamine is to induce Parkinsonism in laboratory
animals to test new medicines for treating Parkinson's disease in
humans. The scientists studied the effects of myricetin on
6-hydroxydopamine-induced neurodegeneration in the substantia
nigra-striatum system and found that myricetin restored the
dopamine content in the striatum.
[1] Three distinct neuroprotective functions of myricetin against
glutamate-induced neuronal cell death: involvement of direct
inhibition of caspase-3. J Neurosci Res. 2008 Jun;86(8):1836-45
[2] Myricetin reduces 6-hydroxydopamine-induced dopamine neuron
degeneration in rats. Neuroreport. 2007 Jul 16;18(11):1181-5.
http://www.phytochemicals.info/phytochemicals/myricetin/brain-health.php
Myricetin affords protection
against peroxynitrite-mediated DNA damage and hydroxyl radical
formation.
Chen W, Li Y, Li J, Han Q, Ye L, Li A.
Food Chem Toxicol. 2011 Sep;49(9):2439-44. Epub 2011 Jun 30.
Source: College of Food Science and Biotechnology, Zhejiang
Gongshang University, Hangzhou 310035, China.
Abstract
Peroxynitrite has been extensively implicated in the pathogenesis
of various forms of neurodegenerative disorders via its cytotoxic
effects, this study was undertaken to investigate whether the
neuroprotective effect of myricetin is associated with inhibition
of peroxynitrite-mediated DNA damage, a critical event leading to
peroxynitrite elicited cytotoxicity. We observed that
peroxynitrite can cause DNA damage in ϕX-174 plasmid DNA and rat
primary astrocytes. The presence of myricetin at physiological
concentration was found to significantly inhibit DNA strand
breakage induced by both peroxynitrite and its generator
3-morpholinosydnonimine (SIN-1). Moreover, the consumption of
oxygen caused by SIN-1 was found to be decreased in the presence
of myricetin, indicating that myricetin might affect the
auto-oxidation of SIN-1. Furthermore, EPR spectroscopy
demonstrated that the formation of DMPO-hydroxyl radical adduct
(DMPO-OH) from peroxynitrite, and that myricetin inhibited the
adduct signal in a concentration-dependent manner. Taken together,
these results demonstrate for the first time that myricetin can
inhibit peroxynitrite-mediated DNA damage and hydroxyl radical
formation.
PMID: 21741426 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21741426
Full Text: http://hnjzxbs.com/Myricetin%20affords%20protection%20against%20peroxynitrite-mediated%20DNA%20damage%20and%20hydroxyl%20radical%20formation.pdf
Myricetin is also known as
Cannabiscetin, Myricetol, Myricitin [check these!]
http://www.altiusdirectory.com/Lifestyle/myricetin-supplements.html
Multiple System Atrophy (MSA):
“…alpha-synuclein (alphaS)…
Lewy body diseases (LBD) and multiple system atrophy (MSA)…”
Antioxidant compounds have
potent anti-fibrillogenic and fibril-destabilizing effects for
alpha-synuclein fibrils in vitro.
Ono K, Yamada M.
J Neurochem. 2006 Apr;97(1):105-15. Epub 2006 Mar 8.
Source: Department of Neurology and Neurobiology of Aging,
Kanazawa University Graduate School of Medical Science, Kanazawa,
Japan.
Abstract
The aggregation of alpha-synuclein (alphaS) in the brain has been
implicated as a critical step in the development of Lewy body
diseases (LBD) and multiple system atrophy (MSA). Various
antioxidants not only inhibit the formation of beta-amyloid
fibrils (fAbeta), but also destabilize preformed fAb in vitro.
Using fluorescence spectroscopy with thioflavin S and electron
microscopy, here we examined the effects of the antioxidants
nordihydroguaiaretic acid, curcumin, rosmarinic acid, ferulic
acid, wine-related polyphenols [tannic acid, myricetin, kaempferol
(+)-catechin and (-)-epicatechin], docosahexaenoic acid,
eicosapentaenoic acid, rifampicin and tetracycline on the
formation of alphaS fibrils (falphaS) and on preformed falphaS.
All molecules, except for docosahexaenoic acid and
eicosapentaenoic acid, dose-dependently inhibited the formation of
falphaS. Moreover, these molecules dose-dependently destabilized
preformed falphaS. The overall activity of the molecules examined
was in the order of: tannic acid=nordihydroguaiaretic
acid=curcumin=rosmarinic acid=myricetin>kaempferol=ferulic
acid>(+)-catechin=(-)-epicatechin>rifampicin=tetracycline.
These compounds with anti-fibrillogenic as well as antioxidant
activities could be key molecules for the development of
preventives and therapeutics for LBD and MSA as well as
Alzheimer's disease.
PMID: 16524383 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/16524383
Curcumin reduces α-synuclein
induced cytotoxicity in Parkinson's disease cell model
Min S Wang1,2, Shanta Boddapati1, Sharareh Emadi1 and Michael R
Sierks1*
* Corresponding author: Michael R Sierks sierks@asu.edu
Author Affiliations
1 Department of Chemical Engineering, Arizona State University,
Tempe, AZ 85287-6006 USA
2 Department of Chemistry, University of Colorado Denver, Denver,
CO 80217-3364 USA
BMC Neuroscience 2010, 11:57 doi:10.1186/1471-2202-11-57
http://www.biomedcentral.com/1471-2202/11/57
Curcumin reduces alpha-synuclein
induced cytotoxicity in Parkinson's disease cell model.
Wang MS, Boddapati S, Emadi S, Sierks MR.
BMC Neurosci. 2010 Apr 30;11:57.
Source: Department of Chemical Engineering, Arizona State
University, Tempe, AZ 85287-6006, USA.
Abstract
BACKGROUND:
Overexpression and abnormal accumulation of aggregated
alpha-synuclein (alphaS) have been linked to Parkinson's disease
(PD) and other synucleinopathies. alphaS can misfold and adopt a
variety of morphologies but recent studies implicate oligomeric
forms as the most cytotoxic species. Both genetic mutations and
chronic exposure to neurotoxins increase alphaS aggregation and
intracellular reactive oxygen species (ROS), leading to
mitochondrial dysfunction and oxidative damage in PD cell models.
RESULTS:
Here we show that curcumin can alleviate alphaS-induced toxicity,
reduce ROS levels and protect cells against apoptosis. We also
show that both intracellular overexpression of alphaS and
extracellular addition of oligomeric alphaS increase ROS which
induces apoptosis, suggesting that aggregated alphaS may induce
similar toxic effects whether it is generated intra- or
extracellulary.
CONCLUSIONS:
Since curcumin is a natural food pigment that can cross the blood
brain barrier and has widespread medicinal uses, it has potential
therapeutic value for treating PD and other neurodegenerative
disorders.
PMID: 20433710 [PubMed] PMCID: PMC2879277
http://www.ncbi.nlm.nih.gov/pubmed/20433710
Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879277/?tool=pubmed
http://www.biomedcentral.com/content/pdf/1471-2202-11-57.pdf
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Known sources:
http://www.vitacost.com/source-naturals-myricetin-100-mg-60-tablets
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Natural sources:
Walnuts, blueberries (2.66
milligrams (mg) per 100 grams (g)), cranberries (6.78mg per 100g)
and red onions (2.7mg per 100g)
[ Don’t know where they got these numbers from: Article Source: http://EzineArticles.com/6206018]
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References:
Multifunction
of myricetin on A beta: neuroprotection via a conformational
change of A beta and reduction of A beta via the interference of
secretases.
Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H.
J Neurosci Res. 2008 Feb 1;86(2):368-77.
Source: Department of Neuroscience for Drug Discovery, Graduate
School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Abstract
Myricetin (3,3',4',5,5',7-hexahydroxyflavone) is classified as a
flavonoid with strong antioxidant effects. Oxidative stress plays
a key role in various neurological diseases such as ischemia and
Alzheimer's disease (AD). To elucidate whether myricetin could
counter the progress of AD, we examined the effects of myricetin
on neurotoxicity induced by beta-amyloid (A beta), a component of
senile plaques in the AD brain. We found that cultured rat primary
cortical neurons treated for 48 hr with A beta1-42 (1 microM)
induced significant neuronal injury. Conformationally altered A
beta1-42 caused apoptotic changes, such as nuclear fragmentation,
as shown by DAPI staining. Pre- and simultaneous administration of
myricetin and A beta1-42 reduced A beta neurotoxicity in a
concentration-dependent manner. By using circular dichroism
spectroscopy and a thioflavin T binding assay, we show that
myricetin (10 microM, 48 hr) prevented structural changes in A
beta1-42 from a random coil to a beta-sheet-rich structure. A
beta1-42-induced apoptotic changes and caspase-3 activation were
reduced by myricetin treatment. Furthermore, we determined that
administration of myricetin significantly decreased A beta1-40 and
A beta1-42 levels in culture media. These effects were based on
two mechanisms: the activation and up-regulation of
alpha-secretase (ADAM10) protein levels as indicated by
fluorescence resonance energy transfer (FRET) assay and immunoblot
analysis and the direct binding and inhibition of beta-secretase
(BACE-1) indicated by cell-free FRET assays. Evidently, myricetin
has multiple functions to counter the progress of AD by the
reduction of A beta production and the detoxification of A beta
through a structural change.
PMID: 17722071 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/17722071
Phenolic compounds prevent amyloid β-protein
oligomerization and synaptic dysfunction by site specific
binding
Kenjiro Ono1, Lei Li2, Yusaku Takamura3, Yuji Yoshiike4, Lijun
Zhu2, Fang Han2, Xian Mao2, Tokuhei Ikeda1, Jun-ichi Takasaki1,
Hisao Nishijo3, Akihiko Takashima4, David B. Teplow5, Michael G.
Zagorski2 and Masahito Yamada1
First Published on March 5, 2012, doi: 10.1074/jbc.M111.325456
jbc.M111.325456.
First Published on March 5, 2012, doi: 10.1074/jbc.M111.325456
April 27, 2012 The Journal of Biological Chemistry, 287,
14631-14643.
Abstract
Cerebral deposition of amyloid β-protein (Aβ) is an invariant
feature of Alzheimer's disease (AD), and epidemiological evidence
suggests that moderate consumption of foods enriched with phenolic
compounds reduce the incidence of AD. We previously reported that
the phenolic compounds myricetin (Myr) and rosmarinic acid (RA)
inhibited Aβ aggregation in vitro and in vivo. To elucidate a
mechanistic basis for these results, we analyzed the effects of
five phenolic compounds in the Aβ aggregation process and in
oligomer-induced synaptic toxicities. We now report that the
phenolic compounds blocked Aβ oligomerization, and Myr promoted
significant NMR chemical shift changes of monomeric Aβ. Both Myr
and RA reduced cellular toxicity and synaptic dysfunction of the
Aβ oligomers. These results suggest that Myr and RA may play key
roles in blocking the toxicity and early assembly processes
associated with Aβ through differently binding.
http://www.jbc.org/content/early/2012/03/08/jbc.M111.325456
Full Text: http://www.jbc.org/content/early/2012/03/08/jbc.M111.325456.full.pdf+html
http://www.jbc.org/content/287/18/14631.full.pdf+html
Myricetin: A Naturally Occurring Regulator of
Metal-Induced Amyloid-β Aggregation and Neurotoxicity
Alaina S. DeToma1,†, Dr. Jung-Suk Choi2,†, Joseph J. Braymer1,
Prof. Dr. Mi Hee Lim 1,2,*Article first published online: 28 APR
2011
DOI: 10.1002/cbic.201000790
http://onlinelibrary.wiley.com/doi/10.1002/cbic.201000790/abstract
Myricetin: a naturally occurring regulator of
metal-induced amyloid-β aggregation and neurotoxicity.
DeToma AS, Choi JS, Braymer JJ, Lim MH.
Chembiochem. 2011 May 16;12(8):1198-201. doi:
10.1002/cbic.201000790. Epub 2011 Apr 28.
Source: Department of Chemistry, University of Michigan, Ann
Arbor, MI 48109-1055, USA.
PMID: 21538759 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21538759
[From a post “Myricetin suppresses iron neurodegeneration”
http://forum.lowcarber.org/archive/index.php/t-339842.html
See also ”Iron metabolism in Parkinsonian syndromes.”
http://www.ncbi.nlm.nih.gov/pubmed/16817199
(double check this link!)
CBD is a Parkinsonian Syndrome]
Myricetin reduces 6-hydroxydopamine-induced
dopamine neuron degeneration in rats.
Ma ZG, Wang J, Jiang H, Liu TW, Xie JX.
Neuroreport. 2007 Jul 16;18(11):1181-5.
Source: Department of Physiology, Faculty of Medicine,
Neuroscience Research Center of Shandong Province, Qingdao
University, Qingdao, Shandong, PR China.
Abstract
The effects of myricetin on 6-hydroxydopamine (6-OHDA)-induced
neurodegeneration in the substantia nigra-striatum system were
investigated. By high-performance liquid chromatography
electrochemical detection, we showed that the dopamine content in
the striatum decreased after 6-OHDA treatment, which could be
restored by myricetin. The immunohistochemistry and
semiquantitative reverse transcription-PCR studies showed that
myricetin could prevent the 6-OHDA-induced decrease of tyrosine
hydroxylase positive neurons and the tyrosine hydroxylase mRNA
expression in the substantia nigra. Perls' iron staining study
further demonstrated that myricetin prevented the 6-OHDA-induced
increase of iron-staining cells in the substantia nigra. These
results suggested that the protective effects of myricetin on the
toxicity of 6-OHDA could be attributed to the myricetin-suppressed
iron toxicity.
PMID: 17589323 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/17589323
Iron metabolism in Parkinsonian syndromes.
Berg D, Hochstrasser H.
Mov Disord. 2006 Sep;21(9):1299-310.
Source: Hertie Institute of Clinical Brain Research and Department
of Medical Genetics, University of Tübingen, Germany.
daniela.berg@uni-tuebingen.de
Abstract
Growing evidence suggests an involvement of iron in the
pathophysiology of neurodegenerative diseases. Several of the
diseases are associated with parkinsonian syndromes, induced by
degeneration of basal ganglia regions that contain the highest
amount of iron within the brain. The group of neurodegenerative
disorders associated with parkinsonian syndromes with increased
brain iron content can be devided into two groups: (1)
parkinsonian syndromes associated with brain iron accumulation,
including Parkinson's disease, diffuse Lewy body disease,
parkinsonian type of multiple system atrophy, progressive
supranuclear palsy, corticobasal ganglionic degeneration, and
Westphal variant of Huntington's disease; and (2) monogenetically
caused disturbances of brain iron metabolism associated with
parkinsonian syndromes, including aceruloplasminemia, hereditary
ferritinopathies affecting the basal ganglia, and panthotenate
kinase associated neurodegeneration type 2. Although it is still a
matter of debate whether iron accumulation is a primary cause or
secondary event in the first group, there is no doubt that
iron-induced oxidative stress contributes to neurodegeneration.
Parallels concerning pathophysiological as well as clinical
aspects can be drawn between disorders of both groups. Results
from animal models and reduction of iron overload combined with at
least partial relief of symptoms by application of iron chelators
in patients of the second group give hope that targeting the iron
overload might be one possibility to slow down the
neurodegenerative cascade also in the first group of inevitably
progressive neurodegenerative disorders
PMID: 16817199 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/16817199
[ This one makes me sad because I knew about the iron
connection. Myricetin was available in 2008, but I didn’t
know about it. ]
Phenolic compounds prevent Alzheimer's
pathology through different effects on the amyloid-beta
aggregation pathway.
Hamaguchi T, Ono K, Murase A, Yamada M.
Am J Pathol. 2009 Dec;175(6):2557-65. Epub 2009 Nov 5.
Source: Department of Neurology and Neurobiology of Aging,
Kanazawa University Graduate School of Medical Science,
Takara-machi, Kanazawa, Japan.
Abstract
Inhibition of amyloid-beta (Abeta) aggregation is an attractive
therapeutic strategy for Alzheimer's disease (AD). Certain
phenolic compounds have been reported to have anti-Abeta
aggregation effects in vitro. This study systematically
investigated the effects of phenolic compounds on AD model
transgenic mice (Tg2576). Mice were fed five phenolic compounds
(curcumin, ferulic acid, myricetin, nordihydroguaiaretic acid
(NDGA), and rosmarinic acid (RA)) for 10 months from the age of 5
months. Immunohistochemically, in both the NDGA- and RA-treated
groups, Abeta deposition was significantly decreased in the brain
(P < 0.05). In the RA-treated group, the level of Tris-buffered
saline (TBS)-soluble Abeta monomers was increased (P < 0.01),
whereas that of oligomers, as probed with the A11 antibody
(A11-positive oligomers), was decreased (P < 0.001). However,
in the NDGA-treated group, the abundance of A11-positive oligomers
was increased (P < 0.05) without any change in the levels of
TBS-soluble or TBS-insoluble Abeta. In the curcumin- and
myricetin-treated groups, changes in the Abeta profile were
similar to those in the RA-treated group, but Abeta plaque
deposition was not significantly decreased. In the ferulic
acid-treated group, there was no significant difference in the
Abeta profile. These results showed that oral administration of
phenolic compounds prevented the development of AD pathology by
affecting different Abeta aggregation pathways in vivo. Clinical
trials with these compounds are necessary to confirm the anti-AD
effects and safety in humans.
PMID: 19893028 [PubMed] PMCID: PMC2789642
http://www.ncbi.nlm.nih.gov/pubmed/19893028
Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789642/?tool=pubmed
Potent anti-amyloidogenic and
fibril-destabilizing effects of polyphenols in vitro:
implications for the prevention and therapeutics of Alzheimer's
disease.
Ono K, Yoshiike Y, Takashima A, Hasegawa K, Naiki H, Yamada M.
J Neurochem. 2003 Oct;87(1):172-81.
Source: Department of Neurology and Neurobiology of Aging,
Kanazawa University Graduate School of Medical Science, Kanazawa
920-8640, Japan.
Abstract
Cerebral deposition of amyloid beta-peptide (Abeta) in the brain
is an invariant feature of Alzheimer's disease (AD). A consistent
protective effect of wine consumption on AD has been documented by
epidemiological studies. In the present study, we used
fluorescence spectroscopy with thioflavin T and electron
microscopy to examine the effects of wine-related polyphenols
(myricetin, morin, quercetin, kaempferol (+)-catechin and
(-)-epicatechin) on the formation, extension, and destabilization
of beta-amyloid fibrils (fAbeta) at pH 7.5 at 37 degrees C in
vitro. All examined polyphenols dose-dependently inhibited
formation of fAbeta from fresh Abeta(1-40) and Abeta(1-42), as
well as their extension. Moreover, these polyphenols
dose-dependently destabilized preformed fAbetas. The overall
activity of the molecules examined was in the order of: myricetin
= morin = quercetin > kaempferol > (+)-catechin =
(-)-epicatechin. The effective concentrations (EC50) of myricetin,
morin and quercetin for the formation, extension and
destabilization of fAbetas were in the order of 0.1-1 micro m. In
cell culture experiments, myricetin-treated fAbeta were suggested
to be less toxic than intact fAbeta, as demonstrated by
3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
assay. Although the mechanisms by which these polyphenols inhibit
fAbeta formation from Abeta, and destabilize pre-formed fAbetain
vitro are still unclear, polyphenols could be a key molecule for
the development of preventives and therapeutics for AD.
PMID: 12969264 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/12969264
Three distinct neuroprotective functions of
myricetin against glutamate-induced neuronal cell death:
involvement of direct inhibition of caspase-3.
Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H.
J Neurosci Res. 2008 Jun;86(8):1836-45.
Source: Department of Neuroscience for Drug Discovery, Graduate
School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Abstract
The excitatory neurotransmitter glutamate can accumulate in the
brain and is thought to be involved in the etiology of many
neurodegenerative disorders, including ischemia and Alzheimer
disease. Therefore, it is important to search for compounds that
reduce glutamate neurotoxicity. This glutamate-mediated
excitotoxicity is caused by intracellular Ca2+ overload via the
N-methyl-D-aspartate receptor NMDAR), reactive oxygen species
(ROS) generation, and caspase-3 activation. Here we show that the
natural flavonoid myricetin inhibited glutamate-induced
excitotoxicity and protected neurons by multiple, distinct
pathways. First, myricetin affected modulation of the NMDAR by
phosphorylation, causing a subsequent reduction in
glutamate-induced intracellular Ca2+ overload. Second, myricetin
inhibited the ROS production caused by glutamate. Finally,
glutamate-induced activation of caspase-3 was reduced by myricetin
treatment. Moreover, myricetin directly interacted with the active
site of caspase-3 via three hydrogen bonds and inhibited its
activity. We conclude that myricetin inhibited glutamate-induced
neuronal toxicity by multiple biochemical pathways. These results
show that myricetin is a potent antineurodegenerative compound and
may contribute to the discovery of a drug with which to combat
neurodegeneration.
PMID: 18265412 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/18265412
Anti-inflammatory activity of
myricetin-3-O-beta-D-glucuronide and related compounds.
A Hiermann, H W Schramm, S Laufer
Inflamm Res. 1998 Nov ;47 (11):421-7 9865500 Cit:9
Institute of Pharmacognosy, University of Graz, Austria.
alois.hiermann@kfunigraz.ac.at
OBJECTIVE AND DESIGN: The anti-inflammatory effect of
myricetinglucuronide (MGL) was investigated and
structurally-related compounds were compared to examine the
structure/activity-relationship in carrageenan-induced rat paw
edema. MATERIALS AND SUBJECTS: In vitro studies were performed
using rat basophilic leukemia (RBL-1) cells, human
polymorphonuclear leukocytes (PMNL), COX-1 from ram seminal
vesicle, COX-2 from sheep placenta and human venous blood. For the
in vivo tests male Wistar rats were used, for the ex vivo test
perfused rabbit ears. TREATMENT: 1-300 microg/kg MGL or
myricetinmethylglucuronate and 0.1-5 mg/kg other related compounds
administered p.o.(carrageenan edema). 5, 50 and 150 microg/kg MGL
p.o. for 14 days (Freund's adjuvant arthritis), 5 and 50 microg/kg
p.o. for 6 days (ulceration). METHODS: Anti-inflammatory effects
were measured in carrageenan edema and in adjuvant arthritis.
Incidence of gastric lesions was tested in an ulcerogenicity model
in vivo. Influence on COX was determined in the perfused rabbit
ear, in PMNL and in a test assay using COX-1 and COX-2. 5-LOX
activity was studied using PMNL and RBL-1. The influence on
platelet aggregation was evaluated measuring light transmission.
RESULTS: MGL exerted a marked and dose-dependent anti-inflammatory
effect in acute (carrageenan edema, ED50 15 microg/kg,
indomethacin ED50 10 mg/kg) and chronic (adjuvant arthritis,
inhibition at 150 microg/kg 18.1 % left paw, 20.6% right paw,
indomethacin 3 mg/kg 18.0% and 19.4%)) models of inflammation. In
the perfused rabbit ear 1 microg MGL inhibited the release of
PGI2, PGD2 and PGE2 to the same extent as 1 microg indomethacin.
The inhibition of COX-1 in the intact cell system was IC50 = 0.5
microM, that of indomethacin 0.0038 microM. In the isolated enzyme
preparations of COX-1 and COX-2 the IC50 was 10 microM and 8
microM, that of indomethacin 9.2 mM and 2.4 microM. In the RBL-1
and PMNL test assay the inhibition of 5-LOX was 0.1 microM and 2.2
microM. An orally administered dose of 50 microg/kg/day induced no
gastric ulcers in rats treated for 6 days. The investigations on
carrageenan edema showed a close relationship between the
structure of MGL and the anti-inflammatory effect. CONCLUSIONS:
MGL is a COX-1, COX-2 and 5-LOX inhibitor. In view of the moderate
in vitro activity and the very potent in vivo activity an additive
mechanism must be involved. Small changes in the molecular
structure lead to the loss or reduction of the anti-inflammatory
activity.
Keywords: pmnl; mgl; cox; lox; microm; anti-inflammatory;
microg/kg; rbl; carrageenan; indomethacin; edema; adjuvant
arthrity; anti-inflammatory activity; rabbit ear; paw;
http://lib.bioinfo.pl/paper:9865500
Myricetin suppresses iron neurodegeneration
http://forum.lowcarber.org/showthread.php?t=339842
USDA Database for the Flavonoid Content of
Selected Foods
http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/flav.pdf
http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/Flav02-1.pdf
http://lpi.oregonstate.edu/infocenter/phytochemicals/flavonoids/
Flavonoid Content of Vegetables
http://www.nal.usda.gov/fnic/foodcomp/Data/Other/AICR03_VegFlav.pdf
Search keywords: Myricetin and Neurodegnerative:
Myricetin and brai health
[sic. Should be: Myricetin and brain health This article needs to be summarized before
publication!!!!!]
Excitotoxicity is the pathological process by which nerve cells
are damaged by glutamate, when receptors for the excitatory
neurotransmitter glutamate, such as the NMDA receptor, are
overactivated. Excitotoxins, high levels of glutamate, reactive
oxygen species generation or caspase-3 activation can cause
excitotoxicity by allowing high levels of calcium ions to enter
the cell. The high level of calcium in the cells activates a
enzymes that can damage cell structures, resulting in diseases
such as Alzheimer. A study conducted by Y Shimmyo and coworkers at
Kyoto University showed that myricetin was a potent
anti-neurodegenerative compound and may contribute to the
discovery of a drug against neurodegeneration [1]. The scientists
came to that conclusion after investigating the effect of
myricetin on neurons. They found that myricetin reduced the
excitotoxicity by different pathways. Myricetin modulated the NMDA
receptor by phosphorylation, resulting in a reduced intracellular
calcium level. Myricetin also inhibited ROS production caused by
glutamate and reduced glutamate-induced activation of caspase-3.
A study by the Qingdao University, China, concluded that myricetin
had protective effect on the toxicity of neurotoxin
6-hydroxydopamine by suppressing iron toxicity [2]. The main use
of 6-hydroxydopamine is to induce Parkinsonism in laboratory
animals to test new medicines for treating Parkinson's disease in
humans. The scientists studied the effects of myricetin on
6-hydroxydopamine-induced neurodegeneration in the substantia
nigra-striatum system and found that myricetin restored the
dopamine content in the striatum.
[1] Three distinct neuroprotective functions of myricetin against
glutamate-induced neuronal cell death: involvement of direct
inhibition of caspase-3. J Neurosci Res. 2008 Jun;86(8):1836-45
[2] Myricetin reduces 6-hydroxydopamine-induced dopamine neuron
degeneration in rats. Neuroreport. 2007 Jul 16;18(11):1181-5.
http://www.phytochemicals.info/phytochemicals/myricetin/brain-health.php
Myricetin affords protection against
peroxynitrite-mediated DNA damage and hydroxyl radical
formation.
Chen W, Li Y, Li J, Han Q, Ye L, Li A.
Food Chem Toxicol. 2011 Sep;49(9):2439-44. Epub 2011 Jun 30.
Source: College of Food Science and Biotechnology, Zhejiang
Gongshang University, Hangzhou 310035, China.
Abstract
Peroxynitrite has been extensively implicated in the pathogenesis
of various forms of neurodegenerative disorders via its cytotoxic
effects, this study was undertaken to investigate whether the
neuroprotective effect of myricetin is associated with inhibition
of peroxynitrite-mediated DNA damage, a critical event leading to
peroxynitrite elicited cytotoxicity. We observed that
peroxynitrite can cause DNA damage in ϕX-174 plasmid DNA and rat
primary astrocytes. The presence of myricetin at physiological
concentration was found to significantly inhibit DNA strand
breakage induced by both peroxynitrite and its generator
3-morpholinosydnonimine (SIN-1). Moreover, the consumption of
oxygen caused by SIN-1 was found to be decreased in the presence
of myricetin, indicating that myricetin might affect the
auto-oxidation of SIN-1. Furthermore, EPR spectroscopy
demonstrated that the formation of DMPO-hydroxyl radical adduct
(DMPO-OH) from peroxynitrite, and that myricetin inhibited the
adduct signal in a concentration-dependent manner. Taken together,
these results demonstrate for the first time that myricetin can
inhibit peroxynitrite-mediated DNA damage and hydroxyl radical
formation.
PMID: 21741426 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21741426
Full Text: http://hnjzxbs.com/Myricetin%20affords%20protection%20against%20peroxynitrite-mediated%20DNA%20damage%20and%20hydroxyl%20radical%20formation.pdf
Multifunction of myricetin on Aβ: Neuroprotection via a
conformational change of Aβ and reduction of Aβ via the
interference of secretases
Yoshiari Shimmyo, Takeshi Kihara,Akinori Akaike,Tetsuhiro
Niidome,Hachiro Sugimoto
Article first published online: 24 AUG 2007
DOI: 10.1002/jnr.21476
http://onlinelibrary.wiley.com/doi/10.1002/jnr.21476/abstract;jsessionid=1A49187547845BCF178B87CDE637FCE0.d04t02?systemMessage=Wiley+Online+Library+will+be+disrupted+on+7+July+from+10%3A00-12%3A00+BST+%2805%3A00-07%3A00+EDT%29+for+essential+maintenance&userIsAuthenticated=false&deniedAccessCustomisedMessage
Multifunction of myricetin on A beta: neuroprotection via a
conformational change of A beta and reduction of A beta via the
interference of secretases.
Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H.
J Neurosci Res. 2008 Feb 1;86(2):368-77.
Source: Department of Neuroscience for Drug Discovery, Graduate
School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Abstract
Myricetin (3,3',4',5,5',7-hexahydroxyflavone) is classified as a
flavonoid with strong antioxidant effects. Oxidative stress plays
a key role in various neurological diseases such as ischemia and
Alzheimer's disease (AD). To elucidate whether myricetin could
counter the progress of AD, we examined the effects of myricetin
on neurotoxicity induced by beta-amyloid (A beta), a component of
senile plaques in the AD brain. We found that cultured rat primary
cortical neurons treated for 48 hr with A beta1-42 (1 microM)
induced significant neuronal injury. Conformationally altered A
beta1-42 caused apoptotic changes, such as nuclear fragmentation,
as shown by DAPI staining. Pre- and simultaneous administration of
myricetin and A beta1-42 reduced A beta neurotoxicity in a
concentration-dependent manner. By using circular dichroism
spectroscopy and a thioflavin T binding assay, we show that
myricetin (10 microM, 48 hr) prevented structural changes in A
beta1-42 from a random coil to a beta-sheet-rich structure. A
beta1-42-induced apoptotic changes and caspase-3 activation were
reduced by myricetin treatment. Furthermore, we determined that
administration of myricetin significantly decreased A beta1-40 and
A beta1-42 levels in culture media. These effects were based on
two mechanisms: the activation and up-regulation of
alpha-secretase (ADAM10) protein levels as indicated by
fluorescence resonance energy transfer (FRET) assay and immunoblot
analysis and the direct binding and inhibition of beta-secretase
(BACE-1) indicated by cell-free FRET assays. Evidently, myricetin
has multiple functions to counter the progress of AD by the
reduction of A beta production and the detoxification of A beta
through a structural change.
PMID:17722071 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/17722071
Inhibition of Heparin-induced Tau Filament Formation by
Phenothiazines, Polyphenols, and Porphyrins*
Sayuri Taniguchi
http://www.jbc.org/content/280/9/7614.full
Full Text: http://www.jbc.org/content/280/9/7614.full.pdf+html
Inhibition of heparin-induced tau filament formation by
phenothiazines, polyphenols, and porphyrins.
Taniguchi S, Suzuki N, Masuda M, Hisanaga S, Iwatsubo T, Goedert
M, Hasegawa M.
J Biol Chem. 2005 Mar 4;280(9):7614-23. Epub 2004 Dec 17.
Source: Department of Molecular Neurobiology, Tokyo Institute of
Psychiatry, Tokyo Metropolitan Organization for Medical Research,
2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Abstract
Tau protein is the major component of the intraneuronal
filamentous inclusions that constitute defining neuropathological
characteristics of Alzheimer's disease and other tauopathies. The
discovery of tau gene mutations in familial forms of
frontotemporal dementia has established that dysfunction of the
tau protein is sufficient to cause neurodegeneration and dementia.
Here we have tested 42 compounds belonging to nine different
chemical classes for their ability to inhibit heparin-induced
assembly of tau into filaments in vitro. Several phenothiazines
(methylene blue, azure A, azure B, and quinacrine mustard),
polyphenols (myricetin, epicatechin 5-gallate, gossypetin, and
2,3,4,2',4'-pentahydroxybenzophenone), and the porphyrin ferric
dehydroporphyrin IX inhibited tau filament formation with IC(50)
values in the low micromolar range as assessed by thioflavin S
fluorescence, electron microscopy, and Sarkosyl insolubility.
Disassembly of tau filaments was observed in the presence of the
porphyrin phthalocyanine. Compounds that inhibited tau filament
assembly were also found to inhibit the formation of Abeta
fibrils. Biochemical analysis revealed the formation of soluble
oligomeric tau in the presence of the inhibitory compounds,
suggesting that this may be the mechanism by which tau filament
formation is inhibited. The compounds investigated did not affect
the ability of tau to interact with microtubules. Identification
of small molecule inhibitors of heparin-induced assembly of tau
will form a starting point for the development of mechanism-based
therapies for the tauopathies.
PMID: 15611092 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/15611092
Full Text: http://www.jbc.org/content/280/9/7614.long
[A long list of citations from some site in Japan]
[Patent by
Genentech, Inc. What exactly are they patenting???]
Modulation of Axon Degeneration
United States Patent Application 20110256150
http://www.freepatentsonline.com/y2011/0256150.html
Structure-activity relationship
of flavonoids derived from medicinal plants in preventing
methylmercury-induced mitochondrial dysfunction.
Franco JL, Posser T, Missau F, Pizzolatti MG, Dos Santos AR, Souza
DO, Aschner M, Rocha JB, Dafre AL, Farina M.
Environ Toxicol Pharmacol. 2010 Nov 1;30(3):272-278.
Source: Departamento de Bioquímica Centro de Ciências Biológicas
Universidade Federal de Santa Catarina, Florianópolis - SC,
Brazil.
Abstract
In the present study, we investigated the potential protective
effects of three flavonoids (myricetin, myricitrin and
rutin) derived from medicinal plants against methyl mercury
(MeHg)-induced mitochondrial dysfunction in vitro... Overall, the
results suggest that MeHg-induced mitotoxicity is associated with
oxidative stress. The ability of myricetin to prevent
MeHg-induced oxidative damage in brain mitochondria renders this
flavonoid a promising molecule for further in vivo studies in the
search for potential antidotes to counteract MeHg-induced
neurotoxicity.
PMID: 21127717 [PubMed]
PMCID: PMC2992974
http://www.ncbi.nlm.nih.gov/pubmed/PMC2992974
Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992974/?tool=pubmed
Neuroprotection by flavonoids.
Dajas F, Rivera-Megret F, Blasina F, Arredondo F, Abin-Carriquiry
JA, Costa G, Echeverry C, Lafon L, Heizen H, Ferreira M, Morquio
A.
Braz J Med Biol Res. 2003 Dec;36(12):1613-20. Epub 2003 Nov 17.
Source: Departamento de Neuroquimica, Instituto de Investigaciones
Biol gicas Clemente Estable, Universidade da Republica,
Montevideo, Uruguay.
Abstract
The high morbidity, high socioeconomic costs and lack of specific
treatments are key factors that define the relevance of brain
pathology for human health and the importance of research on
neuronal protective agents. Epidemiological studies have shown
beneficial effects of flavonoids on arteriosclerosis-related
pathology in general and neurodegeneration in particular.
Flavonoids can protect the brain by their ability to modulate
intracellular signals promoting cellular survival. Quercetin and
structurally related flavonoids (myricetin, fisetin,
luteolin) showed a marked cytoprotective capacity in in vitro
experimental conditions in models of predominantly apoptotic death
such as that induced by medium concentrations (200 M) of H2O2
added to PC12 cells in culture. Nevertheless, quercetin did not
protect substantia nigra neurons in vivo from an oxidative insult
(6-hydroxydopamine), probably due to difficulties in crossing the
blood-brain barrier. On the other hand, treatment of permanent
focal ischemia with a lecithin/quercetin preparation
decreased lesion volume, showing that preparations that help to
cross the blood-brain barrier may be critical for the expression
of the effects of flavonoids on the brain. The hypothesis is
advanced that a group of quercetin-related flavonoids could become
lead molecules for the development of neuroprotective compounds
with multitarget anti-ischemic effects.
PMID: 14666245 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/14666245
Full text: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2003001200002&lng=en&nrm=iso&tlng=en
Inhibition of heparin-induced
tau filament formation by phenothiazines, polyphenols, and
porphyrins.
Taniguchi S, Suzuki N, Masuda M, Hisanaga S, Iwatsubo T, Goedert
M, Hasegawa M.
J Biol Chem. 2005 Mar 4;280(9):7614-23. Epub 2004 Dec 17.
Source: Department of Molecular Neurobiology, Tokyo Institute of
Psychiatry, Tokyo Metropolitan Organization for Medical Research,
2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Abstract
Tau protein is the major component of the intraneuronal
filamentous inclusions that constitute defining neuropathological
characteristics of Alzheimer's disease and other tauopathies. The
discovery of tau gene mutations in familial forms of
frontotemporal dementia has established that dysfunction of the
tau protein is sufficient to cause neurodegeneration and dementia.
Here we have tested 42 compounds belonging to nine different
chemical classes for their ability to inhibit heparin-induced
assembly of tau into filaments in vitro. Several phenothiazines (methylene blue, azure A, azure B,
and quinacrine mustard), polyphenols (myricetin,
epicatechin 5-gallate, gossypetin, and
2,3,4,2',4'-pentahydroxybenzophenone), and the porphyrin ferric
dehydroporphyrin IX inhibited tau filament formation with IC(50)
values in the low micromolar range as assessed by thioflavin S
fluorescence, electron microscopy, and Sarkosyl insolubility.
Disassembly of tau filaments was observed in the presence of the
porphyrin phthalocyanine. Compounds that inhibited tau filament
assembly were also found to inhibit the formation of Abeta
fibrils. Biochemical analysis revealed the formation of soluble
oligomeric tau in the presence of the inhibitory compounds,
suggesting that this may be the mechanism by which tau filament
formation is inhibited. The compounds investigated did not affect
the ability of tau to interact with microtubules. Identification
of small molecule inhibitors of heparin-induced assembly of tau
will form a starting point for the development of mechanism-based
therapies for the tauopathies.
PMID: 15611092 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/15611092
Full text: http://www.jbc.org/content/280/9/7614.long
Cell culture protection and in vivo neuroprotective capacity of
flavonoids.
Dajas F, Rivera F, Blasina F, Arredondo F, Echeverry C, Lafon L,
Morquio A, Heizen H.
Neurotox Res. 2003;5(6):425-32.
Source: Department of Neurochemistry, Instituto de Investigaciones
Biológicas Clemente Estable, Avda Italia 3318, 11600 Montevideo,
Uruguay. fdajas@iibce.edu.uy
Abstract
Flavonoids are an important group of recognized antioxidants
ubiquitous in fruits, vegetables and herbs. There are
epidemiological evidences for the stroke-protecting capacity of
flavonoids and while the neuroprotective power of complex extracts
rich in flavonoids like those of Ginkgo biloba, green tea or
lyophilized red wine have been demonstrated in several studies,
neuroprotection by individual flavonoids has been poorly studied
in vivo. The neuroprotective capacity of individual flavonoids was
studied in PC12 cells in culture and in a model of permanent focal
ischemia (permanent Middle Cerebral Artery Occlusion - pMCAO). In
the in vivo experiments, flavonoids were administered in lecithin
preparations to facilitate the crossing of the blood brain
barrier. The simultaneous incubation of PC12 cells with 200 micro
M hydrogen peroxide (H2O2) and different flavonoids for 30 min
resulted in a conspicuous profile: quercetin, fisetin, luteolin
and myricetin significantly increased cell survival while
catechin, kaempherol and taxifolin did not. Quercetin was detected
in brain tissue 30 min and 1 h after intraperitoneal
administration. When one of the protective flavonoids (quercetin)
and one of those that failed to increase PC12 cell survival
(catechin) were assessed for their protective capacity in the
pMCAO model, administered i.p. 30 min after vessel occlusion,
quercetin significantly decreased the brain ischemic lesion while
catechin did not. It is concluded that when administered in
liposomal preparations, flavonoids structurally related to
quercetin could become leads for the development of a new
generation of molecules to be clinically effective in human brain
ischemia.
PMID: 14715446 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/14715446
Flavonoid permeability across an in situ model of the
blood-brain barrier.
Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ.
Free Radic Biol Med. 2004 Mar 1;36(5):592-604.
Source: Antioxidant Research Group, Wolfson Centre for
Age-Related Diseases, Centre for Neuroscience Research, Guy's
King's and St Thomas's School of Biomedical Sciences, King's
College, London SE1 1UL, UK.
Erratum in Free Radic Biol Med. 2004 May 15;36(10):1342.
Abstract
Understanding mechanisms associated with flavonoid neuroprotection
is complicated by the lack of information on their ability to
enter the CNS. This study examined naringenin and quercetin
permeability across the blood-brain barrier (BBB), using in vitro
(ECV304/C6 coculture) and in situ (rat) models. We report
measurable permeabilities (P(app)) for both flavonoids across the
in vitro BBB model, consistent with their lipophilicity. Both
flavonoids showed measurable in situ BBB permeability. The rates
of uptake (K(in)) into the right cerebral hemisphere were 0.145
and 0.019 ml min(-1) g(-1) for naringenin and quercetin,
respectively. Quercetin K(in) was comparable to that of colchicine
(0.006 ml min(-1) g(-1)), a substrate for P-glycoprotein (P-gp).
Preadministration of the P-gp inhibitor PSC833 or GF120918 (10
mg/kg body wt) significantly increased colchicine K(in), but only
GF120918 (able to inhibit breast cancer resistance protein, BCRP)
affected K(in) for quercetin. Naringenin K(in) was not affected.
The influence of efflux transporters on flavonoid permeability at
the BBB was further studied using MDCK-MDR1 and immortalized rat
brain endothelial cells (RBE4). Colchicine, quercetin, and
naringenin all showed measurable accumulation (distribution
volume, V(d) (microl/mg protein)) in both cell types. The V(d) for
colchicine increased significantly in both cell lines following
coincubation with either PSC833 (25 microM) or GF120918 (25
microM). Both inhibitors also caused an increase in naringenin
V(d); by contrast only GF120918 coincubation significantly
increased quercetin V(d). In conclusion, the results demonstrate
that flavonoids are able to traverse the BBB in vivo. However, the
permeability of certain flavonoids in vivo is influenced by their
lipophilicity and interactions with efflux transporters.
PMID: 14980703 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/14980703
Flavonoids and the aging brain.
Schmitt-Schillig S, Schaffer S, Weber CC, Eckert GP, Müller WE.
J Physiol Pharmacol. 2005 Mar;56 Suppl 1:23-36.
Source: Institute of Pharmacology (ZAFES), Biocenter Niederursel,
University of Frankfurt, Frankfurt am Main, Germany.
Abstract
Like in all other organs, the functional capacity of the human
brain deteriorates over time. Pathological events such as
oxidative stress, due to the elevated release of free radicals and
reactive oxygen or nitrogen species, the subsequently enhanced
oxidative modification of lipids, protein, and nucleic acids, and
the modulation of apoptotic signaling pathways contribute to loss
of brain function. The identification of neuroprotective food
components is one strategy to facilitate healthy brain aging.
Flavonoids were shown to activate key enzymes in mitochondrial
respiration and to protect neuronal cells by acting as
antioxidants, thus breaking the vicious cycle of oxidative stress
and tissue damage. Furthermore, recent data indicate a favorable
effect of flavonoids on neuro-inflammatory events. Whereas most of
these effects have been shown in vitro, limited data in vivo are
available, suggesting a rather low penetration of flavonoids into
the brain. Nevertheless, several reports support the concept that
flavonoid intake inhibits certain biochemical processes of brain
aging, and might thus prevent to some extent the decline of
cognitive functions with aging as well as the development or the
course of neurodegenerative diseases. However, more data are
needed to assess the true impact of flavonoids on brain aging.
PMID: 15800383 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/15800383
Full text: http://www.jpp.krakow.pl/journal/archive/03_05_s1/pdf/23_03_05_s1_article.pdf
Note… myricetin can induce
apoptosis in cancer cells.
http://pi3kaktblog.com/2011/10/10/myricetin-can-inhibit-pi3k-and-induce-apoptosis-in-pancreatic-cancer/
Myricetin induces pancreatic
cancer cell death via the induction of apoptosis and inhibition
of the phosphatidylinositol 3-kinase (PI3K) signaling pathway.
Cancer Lett. 2011 Sep 28;308(2):181-8. Epub 2011 Jun 14.
Phillips PA, Sangwan V, Borja-Cacho D, Dudeja V, Vickers SM,
Saluja AK.
Source: Department of Surgery, University of Minnesota,
Minneapolis, 55455, United States.
Abstract
Pancreatic cancer is the fourth leading cause of cancer related
deaths and is a disease with poor prognosis. It is refractory to
standard chemotherapeutic drugs or to novel treatment
modalities, making it imperative to find new treatments. In this
study, using both primary and metastatic pancreatic cancer cell
lines, we have demonstrated that the flavonoid myricetin induced
pancreatic cancer cell death in vitro via apoptosis, and caused
a decrease in PI3 kinase activity. In vivo, treatment of
orthotopic pancreatic tumors with myricetin resulted in tumor
regression and decreased metastatic spread. Importantly,
myricetin was non-toxic, both in vitro and in vivo, underscoring
its use as a therapeutic agent against pancreatic cancer.
PMID: 21676539
http://www.ncbi.nlm.nih.gov/pubmed/21676539
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