Fate of the flavonoid quercetin in human cell lines: chemical instability and metabolism

Although cell cultures are increasingly being used as models for studying the biological actions of flavonoids, no information on the fate, such as uptake and metabolism, exists for these natural products in these models. This study examined the elimination of quercetin, one of the most abundant fla...

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Bibliographic Details
Published inJournal of pharmacy and pharmacology Vol. 51; no. 3; p. 353
Main Authors Boulton, D W, Walle, U K, Walle, T
Format Journal Article
LanguageEnglish
Published England 01.03.1999
Subjects
Carboxylic Acids - metabolism
Chromatography, High Pressure Liquid
Drug Stability
Flavonoids - metabolism
Gas Chromatography-Mass Spectrometry
Humans
Liver Neoplasms - metabolism
Peroxides - metabolism
Quercetin - chemistry
Quercetin - metabolism
Tumor Cells, Cultured
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Summary:Although cell cultures are increasingly being used as models for studying the biological actions of flavonoids, no information on the fate, such as uptake and metabolism, exists for these natural products in these models. This study examined the elimination of quercetin, one of the most abundant flavonoids, from the cultured human hepatocarcinoma cell line Hep G2 using [14C]-labelled compound with HPLC and LC/MS for structure characterization. These cells showed a 9.6-fold accumulation of quercetin and the formation of an O-methylated metabolite, isorhamnetin. However, a rapid elimination of quercetin, with no unchanged compound present beyond 8 h, was mainly due to oxidative degradation. The initial intermediate reaction appears to involve peroxidation, leading to a dioxetan, as evidenced by a 32-amu increase in the molecular ion by LC/MS. Subsequently, opening of the C-ring leads to the formation of carboxylic acids, the major one identified in this study as protocatechuic acid. A separate reaction results in a polymeric quercetin product which is highly retained on a reversed-phase C18 HPLC column. It is postulated that these degradative and metabolic changes contribute to the multiple biological actions reported for quercetin, using cell culture models. Interestingly, part of the degradative pathway could be inhibited by including nontoxic concentrations of EDTA in the cell culture medium.
ISSN:0022-3573
DOI:10.1211/0022357991772367