quercetin - neuroprotective role of quercetin

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Brain Res. 2011 Apr 6;1383:289-99. Epub 2011 Jan 31.

The role of ASIC1a in neuroprotection elicited by quercetin in focal cerebral ischemia.

Pandey AK, Hazari PP, Patnaik R, Mishra AK.
SourceDivision of Cyclotron & Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Road, Delhi 110054, India.

Abstract
One of the major instigators to neuronal cell death and brain damage following cerebral ischemia is calcium dysregulation.

The intracellular calcium overload resulting from glutamate excitotoxicity is considered a major determinant for neuronal loss during cerebral ischemia. Moreover, ASIC1a activation due to acidosis also promotes intracellular calcium overload during ischemic insult.

Interestingly, ASIC1a was found to be inhibited by some flavonoids which carry an anti-inflammatory property particularly quercetin, which could be exploited in hypoxic conditions like cerebral ischemia.

This encourages us to investigate the neuroprotective effect of quercetin besides its possible downstream signaling mechanism in focal cerebral ischemia.

The treatment of quercetin 30min before ischemia and 4h after reperfusion shows significant protection from ischemic injury as noticed by reduction in cerebral infarct volume and neurobehavioral deficit. In addition to earlier calcium dependent rise in the levels of nitrite and MDA exhibited marked reduction (P<0.01) in their levels when given quercetin pretreatment in ischemic brain regions. The quercetin treatment also reduced the spectrin break down products (SBDP) caused by ischemic activation of calcium dependent protease calpain. In ex-vivo study, it was also observed that quercetin inhibited the acid mediated intracellular calcium levels in rat brain synaptoneurosomes.

These studies suggest the neuroprotective role of quercetin in focal cerebral ischemia by regulation of ASIC1a.Copyright © 2011 Elsevier B.V. All rights reserved.

PMID: 21281608 [PubMed - in process]

1: Biochem Pharmacol 2003 Mar 1;65(5):877-85

Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study.

Hendriks JJ, de Vries HE, van der Pol SM, van den Berg TK, van Tol EA, Dijkstra
CD.

Department of Molecular Cell Biology, VU Medical Centre, Van der Boechorststraat
7, 1081 BT, Amsterdam, The Netherlands.

Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease.

Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds, are able to influence myelin phagocytosis by macrophages in vitro.

The flavonoids luteolin, quercetin and fisetin most significantly decreased the amount of myelin phagocytosed by a macrophage cell line without affecting its viability. IC(50) values for these compounds ranged from 20 to 80 microM. The flavonoid structure appeared to be essential for observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4 positions in combination with a C-2,3 double bond were most effective.The capacity of the various flavonoids to inhibit phagocytosis correlated well with their potency as antioxidant, which is in line with the requirement of reactive oxygen species for the phagocytosis of myelin by macrophages.

Our results implicate that flavonoids may be able to limit the demyelination process during multiple sclerosis.

PMID: 12628496 [PubMed - in process]