University of Hertfordshire

From the same journal

By the same authors

Glial metabolism of quercetin reduces its neurotoxic potential

Research output: Contribution to journalArticle

  • Katerina Vafeiadou
  • David Vauzour
  • Ana Rodriguez-Mateos
  • Matthew Whiteman
  • Robert J. Williams
  • Jeremy P. E. Spencer
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Original languageEnglish
Number of pages6
Pages (from-to)195-200
JournalArchives of Biochemistry and Biophysics
Journal publication date15 Oct 2008
Volume478
Issue2
DOIs
Publication statusPublished - 15 Oct 2008

Abstract

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 addition, 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.

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