Myricetin and quercetin, the flavonoid constituents ofGinkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca2+-loaded brain neurons

Oyama, Yasuo; Fuchs, Paul; Katayama, N.; Noda, Kazuhiro

doi:10.1016/0006-8993(94)91431-1

Cited by 205 publications

(96 citation statements)

References 11 publications

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“…1A) [11]. Quercetin exhibits multiple pharmacological activities in nervous and non-nervous systems [12][13][14][15][16]. However, the underlying cellular mechanisms of quercetin actions are relatively unknown, especially with regards to possible regulation of receptors or ionic channels involved in synaptic transmissions.…”

Section: Introductionmentioning

confidence: 99%

Quercetin Inhibits α3β4 Nicotinic Acetylcholine Receptor-Mediated Ion Currents Expressed inXenopusOocytes

Lee

Hwang

Choi

et al. 2011

Korean J Physiol Pharmacol

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Quercetin mainly exists in the skin of colored fruits and vegetables as one of flavonoids. Recent studies show that quercetin, like other flavonoids, has diverse pharmacological actions. However, relatively little is known about quercetin effects in the regulations of ligand-gated ion channels. In the previous reports, we have shown that quercetin regulates subsets of homomeric ligand-gated ion channels such as glycine, 5-HT3A and α 7 nicotinic acetylcholine receptors. In the present study, we examined quercetin effects on heteromeric neuronal α 3β 4 nicotinic acetylcholine receptor channel activity expressed in Xenopus oocytes after injection of cRNA encoding bovine neuronal α 3 and β 4 subunits. Treatment with acetylcholine elicited an inward peak current (IACh) in oocytes expressing α 3β 4 nicotinic acetylcholine receptor. Co-treatment with quercetin and acetylcholine inhibited IACh in oocytes expressing α 3β 4 nicotinic acetylcholine receptors. The inhibition of IACh by quercetin was reversible and concentration-dependent. The half-inhibitory concentration (IC50) of quercetin was 14.9± 0.8 μ M in oocytes expressing α 3β 4 nicotinic acetylcholine receptor. The inhibition of IACh by quercetin was voltage-independent and non-competitive. These results indicate that quercetin might regulate α 3β 4 nicotinic acetylcholine receptor and this regulation might be one of the pharmacological actions of quercetin in nervous systems.

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Section: Introductionmentioning

confidence: 99%

Quercetin Inhibits α3β4 Nicotinic Acetylcholine Receptor-Mediated Ion Currents Expressed inXenopusOocytes

Lee

Hwang

Choi

et al. 2011

Korean J Physiol Pharmacol

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“…On the other hand, several works have shown that myricetin (3,5,7,3',4',5'-hexa-hydroxyflavone) is a stronger antioxidant than quercetin, what has been attributed to the presence of the 5'-OH group that allows a further stabilization of the myricetin derived semi-quinone radical [17,18]. Briefly, it has been found that myricetin is a stronger brain neuron oxidative stress and liposome oxidation inhibitor than quercetin.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant mechanisms of Quercetin and Myricetin in the gas phase and in solution – a comparison and validation of semi-empirical methods

Justino

Vieira

2009

J Mol Model

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Flavonoids have long been recognized for their general health-promoting properties, of which their antioxidant activity may play an important role. In this work we have studied the properties of two flavonols, quercetin and myricetin, using semi-empirical methods in order to validate the application of the recent Parametric Model 6 and to understand the fundamental difference between the two molecules. Their geometries have been optimized and important molecular properties have been calculated. The energetic of the possible antioxidant mechanisms have also been analyzed. The two studied flavonols do not differ significantly in their molecular properties, but the antioxidant mechanisms by which they may act in solution can be rather different. Moreover, we also show that the Parametric Model 6 can produce reliable information for this type of compounds.Response to Reviewers: Reviewer #1: P.3 "Q" and "M" are used before they are defined. P.5 "Q" and "M" definitions should be given earlier in the paper. P.5 "... what is of extreme." should be ". which is of extreme ." P. 7 HAT has already been defined on p.2, BDE has already been defined. P.4 ". can be stabilized more effectively stabilized ." is very bad English »»» These issues have been properly adressed.P.5 ". determining the biological relevance of these compounds." Does not follow from the preceding part of the sentence. »»» It was an oversimplification of what was meant. We changed it to "indicating that they will be available to interact with surrounding radicals and other species" (pages 5/6).P.8 The statement, "As it can be seen from Table 6, the absolute values obtained are strikingly different from those obtained by other authors at the DFT level." is utterly useless unless the DFT results are also presented. Do the authors intend the reader to stop, search for suitable DFT publications, do the comparison, and then resume reading? »»» We have now included these results in the tables and made the necessary comparisons. Table 6 was split in two - Table 6 for M and Table 7 for Q -and now contain the DFT acidities and BDE values retrieved from the literature. We have also included a new table -Table 8 -which contains the deprotonation and H atom abstraction orders from the literature as well as from our work.P.8 For the authors to say that ". the calculated heats of formation of H+ and H*, that need to be further refined." is meaningless. They can say that PM6 gives very inaccurate values for these quantities. The implication that further refinement would give better values is not supported by any evidence. »»» As a consequence of this remark, as well as of the remarks of the Reviewer #2, we have repeated the calculations using the same method but under much more stringent conditions and also using other methods. These new calculations led to heats of formation of H* and H+ of, respectively, 217.99 (which is the accepted reference value, a parameter in the program) and 1303.16 kJ/mol, which differs about 15 % from the accepted reference value of 1...

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“…Although the flavonol quercetin is one of the most frequently researched flavonoids, with evidence for both its beneficial (13,14) and deleterious effects (15,16) on different cell types, its mechanism of action remains unclear. Furthermore, recent evidence has shown that quercetin is extensively metabolized to O-methylated and glucuronide metabolites during absorption in the small intestine and in the liver (17,18), and such metabolites should be taken into consideration to provide in vivo relevance for any mechanism.…”

mentioning

confidence: 99%

Modulation of Pro-survival Akt/Protein Kinase B and ERK1/2 Signaling Cascades by Quercetin and Its in Vivo Metabolites Underlie Their Action on Neuronal Viability

Spencer

Rice‐Evans

Williams

2003

Journal of Biological Chemistry

311

224

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Much recent interest has focused on the potential of flavonoids to interact with intracellular signaling pathways such as with the mitogen-activated protein kinase cascade. We have investigated whether the observed strong neurotoxic potential of quercetin in primary cortical neurons may occur via specific and sensitive interactions within neuronal mitogen-activated protein kinase and Akt/protein kinase B (PKB) signaling cascades, both implicated in neuronal apoptosis. Quercetin induced potent inhibition of both Akt/PKB and ERK phosphorylation, resulting in reduced phosphorylation of BAD and a strong activation of caspase-3. High quercetin concentrations (30 M) led to sustained loss of Akt phosphorylation and subsequent Akt cleavage by caspase-3, whereas at lower concentrations (<10 M) the inhibition of Akt phosphorylation was transient and eventually returned to basal levels. Lower levels of quercetin also induced strong activation of the pro-survival transcription factor cAMP-responsive element-binding protein, although this did not prevent neuronal damage. O-Methylated quercetin metabolites inhibited Akt/PKB to lesser extent and did not induce such strong activation of caspase-3, which was reflected in the lower amount of damage they inflicted on neurons. In contrast, neither quercetin nor its O-methylated metabolites had any measurable effect on c-Jun N-terminal kinase phosphorylation. The glucuronide of quercetin was not toxic and did not evoke any alterations in neuronal signaling, probably reflecting its inability to enter neurons. Together these data suggest that quercetin and to a lesser extent its O-methylated metabolites may induce neuronal death via a mechanism involving an inhibition of neuronal survival signaling through the inhibition of both Akt/PKB and ERK rather than by an activation of the c-Jun N-terminal kinase-mediated death pathway.

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Myricetin and quercetin, the flavonoid constituents ofGinkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca2+-loaded brain neurons

Cited by 205 publications

References 11 publications

Quercetin Inhibits α3β4 Nicotinic Acetylcholine Receptor-Mediated Ion Currents Expressed inXenopusOocytes

Quercetin Inhibits α3β4 Nicotinic Acetylcholine Receptor-Mediated Ion Currents Expressed inXenopusOocytes

Antioxidant mechanisms of Quercetin and Myricetin in the gas phase and in solution – a comparison and validation of semi-empirical methods

Modulation of Pro-survival Akt/Protein Kinase B and ERK1/2 Signaling Cascades by Quercetin and Its in Vivo Metabolites Underlie Their Action on Neuronal Viability

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