Myricetin reduces 6-hydroxydopamine-induced dopamine neuron degeneration in rats

Ma, Zegang; Wang, Jun; Jiang, Hong; Liu, Tianwei; Xie, Junxia

doi:10.1097/wnr.0b013e32821c51fe

Cited by 48 publications

(31 citation statements)

References 15 publications

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“…6-OHDAtreated animals exhibit the major hallmarks of PD, including loss of dopaminergic neurons in the SN. In the present study, we observed increased iron levels in the SN of PD models where dopaminergic neuronal degeneration was found, in accordance with our previous studies as well as with those of others [7,21,22]. Ferrous iron is harmful to cells because of its ability to react with hydrogen peroxide to form highly reactive hydroxyl radicals.…”

Section: Discussionsupporting

confidence: 80%

Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent

et al. 2010

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Iron plays a key role in Parkinson's disease (PD). Increased iron content of the substantia nigra (SN) has been found in PD patients, and divalent metal transporter 1 (DMT1) has been shown to be up-regulated in the SN of both MPTP-induced PD models and PD patients. However, the mechanisms underlying DMT1 up-regulation are largely unknown. In the present study, we observed that in the SN of 6-hydroxydopamine (6-OHDA)-induced PD rats, DMT1 with the iron responsive element (IRE, DMT1+IRE), but not DMT1 without IRE (DMT1−IRE), was upregulated, suggesting that increased DMT1+IRE expression might account for nigral iron accumulation in PD rats. This possibility was further assessed in an in vitro study using 6-OHDA-treated and DMT1+IRE-over-expressing MES23.5 cells.

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Section: Discussionsupporting

confidence: 80%

Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent

et al. 2010

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“…Myricetin (2, 5, 7, 3′, 4′, 5′-pentahydroxylflavonol) is a widely distributed flavonoid [14], which has been reported to have a variety of biological effects, such as anticancer, antioxidant, antidiabetic, prevention of apoptosis, and neuron degeneration [14–17]. Myricetin is also an important bioactive compound present in some medicinal herbs, for example, St. John's Wort [18], which have hypnotic and antidepressant effects.…”

Section: Introductionmentioning

confidence: 99%

Flavonoid Myricetin ModulatesGABAAReceptor Activity through Activation of
Zhang
¹
,
Gang
²
,
Rowlands
³

et al. 2012
Evidence-Based Complementary and Alternative Medicine
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The flavonoid myricetin is found in several sedative herbs, for example, the St. John's Wort, but its influence on sedation and its possible mechanism of action are unknown. Using patch-clamp technique on a brain slice preparation, the present study found that myricetin promoted GABAergic activity in the neurons of hypothalamic paraventricular nucleus (PVN) by increasing the decay time and frequency of the inhibitory currents mediated by GABAA receptor. This effect of myricetin was not blocked by the GABAA receptor benzodiazepine- (BZ-) binding site antagonist flumazenil, but by KN-62, a specific inhibitor of the Ca2+/calmodulin-stimulated protein kinase II (CaMK-II). Patch clamp and live Ca2+ imaging studies found that myricetin could increase Ca2+ current and intracellular Ca2+ concentration, respectively, via T- and L-type Ca2+ channels in rat PVN neurons and hypothalamic primary culture neurons. Immunofluorescence staining showed increased phosphorylation of CaMK-II after myricetin incubation in primary culture of rat hypothalamic neurons, and the myricetin-induced CaMK-II phosphorylation was further confirmed by Western blotting in PC-12 cells. The present results suggest that myricetin enhances GABAA receptor activity via calcium channel/CaMK-II dependent mechanism, which is distinctively different from that of most existing BZ-binding site agonists of GABAA receptor.

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“…A high level of iron has been found in the SN of parkinsonian [28] and PD mouse models [17,19,[29][30][31][32][33][34][35] , where α-synuclein aggregation also exists.…”

Section: Discussionmentioning

confidence: 99%

Dose- and time-dependent α-synuclein aggregation induced by ferric iron in SK-N-SH cells

Jiang

Song

et al. 2010

Neurosci. Bull.

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Objective Intracellular formation of Lewy body (LB) is one of the hallmarks of Parkinson's disease. The main component of LB is aggregated α-synuclein, present in the substantia nigra where iron accumulation also occurs. The present study was aimed to study the relationship between iron and α-synuclein aggregation. Methods SK-N-SH cells were treated with different concentrations of ferric iron for 24 h or 48 h. MTT assay was conducted to determine the cell viability.Thioflavine S staining was used to detect α-synuclein aggregation. Results With the increase of iron concentration, the cell viability decreased significantly. At the concentrations of 5 mmol/L and 10 mmol/L, iron induced α-synuclein aggregation more severely than at the concentration of 1 mmol/L. Besides, 48-h treatment-induced aggregation was more severe than that induced by 24-h treatment, at the corresponding iron concentrations. Conclusion Ferric iron can induce α-synuclein aggregation, which is toxic to the cells, in a dose-and time-dependent way.

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Myricetin reduces 6-hydroxydopamine-induced dopamine neuron degeneration in rats

Cited by 48 publications

References 15 publications

Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent

Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent

Flavonoid Myricetin ModulatesGABAAReceptor Activity through Activation of
Zhang
¹
,
Gang
²
,
Rowlands
³

et al. 2012
Evidence-Based Complementary and Alternative Medicine
17
1
19
0
View full text Add to dashboard Cite

Dose- and time-dependent α-synuclein aggregation induced by ferric iron in SK-N-SH cells

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Myricetin reduces 6-hydroxydopamine-induced dopamine neuron degeneration in rats

Cited by 48 publications

References 15 publications

Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent

Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent

Flavonoid Myricetin ModulatesGABAAReceptor Activity through Activation ofZhang1, Gang2, Rowlands3 et al. 2012Evidence-Based Complementary and Alternative Medicine171190View full textAdd to dashboardCite

Dose- and time-dependent α-synuclein aggregation induced by ferric iron in SK-N-SH cells

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Flavonoid Myricetin ModulatesGABAAReceptor Activity through Activation of
Zhang
¹
,
Gang
²
,
Rowlands
³

et al. 2012
Evidence-Based Complementary and Alternative Medicine
17
1
19
0
View full text Add to dashboard Cite