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 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.
Boulton
D W
DW
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA.
Walle
U K
UK
Walle
T
T
D002264:Carboxylic Acids / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005419:Flavonoids / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism; D011794:Quercetin / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002264:Carboxylic Acids; D005419:Flavonoids; D010545:Peroxides; D011794:Quercetin