Identification of 14 Quercetin Phase II Mono- and Mixed Conjugates and Their Formation by Rat and Human Phase II in Vitro Model Systems

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• 作者：Hester van der Woude ; Marelle G. Boersma ; Jacques Vervoort ; and Ivonne M. C. M. Rietjens
• 刊名：Chemical Research in Toxicology
• 出版年：2004
• 出版时间：November 2004
• 年：2004
• 卷：17
• 期：11
• 页码：1520 - 1530
• 全文大小：137K
• 年卷期：v.17,no.11(November 2004)
• ISSN：1520-5010

文摘

In this study, the HPLC, UV-vis, LC-MS, and ¹H NMR characteristics of 14 different phaseII mono- and mixed conjugates of quercetin were determined, providing a useful tool in theidentification of quercetin phase II metabolite patterns in various biological systems. Usingthese data, the phase II metabolism of quercetin by different rat and human liver and intestinein vitro models, including cell lines, S9 samples, and hepatocytes, was investigated. Acomparison of quercetin phase II metabolism between rat and human liver and intestinal celllines, S9, and hepatocytes showed considerable variation in the nature and ratios of quercetinconjugate formation. It could be established that the intestine contributes significantly to thephase II metabolism of quercetin, especially to its sulfation, that organ-dependent phase IImetabolism in rat and man differ significantly, and that human interindividual variation ishigher for quercetin sulfation than for glucuronidation or methylation. Furthermore, quercetinconjugation by different in vitro models from corresponding origins may differ significantly.The identification of the various mono- and mixed quercetin phase II conjugates revealedsignificant differences in phase II conjugation by a variety of in vitro models and led to theconclusion that none of the in vitro models converted quercetin to a phase II metabolite mixturesimilar to the in vivo plasma metabolite pattern of quercetin. Altogether, the identification ofa wide range of phase II metabolites of quercetin as presented in this study allows thedetermination of quercetin phase II biotransformation patterns and opens the way for a better-funded assessment of the biological activity of quercetin in a variety of biological systems.