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Glial metabolism of quercetin reduces its neurotoxic potential

Vafeiadou, K., Vauzour, D., Rodriguez-Mateos, A., Whiteman, M., Williams, R. J. and Spencer, J. P. E. (2008) Glial metabolism of quercetin reduces its neurotoxic potential. Archives of Biochemistry and Biophysics, 478 (2). pp. 195-200. ISSN 0003-9861

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To link to this article DOI: 10.1016/j.abb.2008.07.014

Abstract/Summary

The neuroprotective effects of flavonoids will ultimately depend on their interaction with both neuronal and glial cells. in this study, we show that the potential neurotoxic effects of quercetin are modified by glial cell interactions. Specifically, quercetin is rapidly conjugated to glutathione within glial cells to yield 2 '-glutathionyl-quercetin, which is exported from cells but has significantly reduced neurotoxicity. In addion, quercetin underwent intracellular O-methylation to yield 3 '-O-methyl-quercetin and 4 '-O-methyl-quercetin, although these were not exported from glia at the same rate as the glutathionyl adduct. The neurotoxic potential of both quercetin and 2 '-glutathionyl-quercetin paralleled their ability to modulate the pro-survival Akt/PKB and extracellular signal-regulated kinase (ERK) signalling pathways. These data were supported by co-culture investigation, where the neurotoxic effects of quercetin were significantly reduced when they were cultured alongside glial cells. We propose that glial cells act to protect neurons against the neurotoxic effects of quercetin and that 2 '-glutathionyl-quercetin represents a novel quercetin metabolite. (c) 2008 Elsevier Inc. All rights reserved.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
ID Code:12911
Uncontrolled Keywords:flavonoid, quercetin, glutathione, neuron, neurotoxicity, glia, brain, in-vivo metabolites, cell-cycle arrest, oxidative stress, behavioral, deficits, parkinsons-disease, signaling pathway, cortical-neurons, cancer-cells, brain, glutathione, Animals, Biotransformation,Cell Survival/drug effects, Cells, Cultured Mice, Neuroglia/cytology/*drug effects/*metabolism, Neuroprotective Agents/metabolism/pharmacokinetics/pharmacology, Neurotoxins/*metabolism/pharmacokinetics/*toxicity, Quercetin/*metabolism/pharmacokinetics/*toxicity
Publisher:Elsevier

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