Effect of Flavonoids on Phase II Metabolism

Although quercetin may stimulate UGT, it inhibits human hepatic sulfation of resveratrol, acetaminophen, dopamine, (-)-salbutamol, minoxidil, and paracetamol in vitro.69,98-101 This inhibition may be chemopreventive, as activation of some promutagens occurs via SULT reactions.68 However, SULT inhibition may also lead to the accumulation of some xenobiotics and possible toxicity. The magnitude of inhibition by quercetin of SULT appears dependent on the isoform because SULT1A3 is less affected than other isoforms, suggesting a tissue-dependent effect of quercetin.69 

COMT methylates quercetin to form isorhamnetin and tamarixetin, but quercetin can inhibit COMT methylation of catechol estrogens in human liver and mammary cells102-103 as well as hamster liver and kidney cells.104 In contrast to an acute dose, consumption of quercetin for 10 days by rats altered the position of methylation, as tamarixetin was undetected in the circulation.92 

Although flavonoids can modulate UGT, SULT, and COMT activity toward other xenobiotics, their impact after chronic consumption on their own metabolism has not been examined, even though such activity could substantially alter their bioactivity.105-107 This relationship may become even more complex in older subjects due to the inverse association between age and the adaptability of phase II metabolism.42-108 

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