The identification and characterisation of quercetin metabolites in humans and rats

Quercetin is a dietary flavonoid, known to possess a range of biological properties of in in vitro systems. These properties may be of potential therapeutic benefit against certain diseases. Considerable work has focused on its antioxidant capability, which has been shown to be more powerful than that of vitamin E.;Quercetin also has antineoplastic activity, and at 10M it inhibits the proliferation of malignant cell lines derived from breast, ovarian and gastrointestinal tumours and leukaemias. Therefore, a phase I clinical trial on cancer patients was conducted at the Queen Elizabeth Hospital in Birmingham, UK, in which quercetin was administered intravenously. One patient received quercetin p.o. In parallel to this clinical trial, blood and urine, derived from rats, were analysed in order to study the metabolism of quercetin, and the elucidate its bioavailability in vivo.;The results show that metabolism by F344 rats, which received quercetin i.v., reflected adequately the metabolism seen in humans. Furthermore, analysis of both human and rat samples demonstrated that quercetin is rapidly metabolised via phase II biotransformation pathways to methyl, sulphate and glucuronide conjugates, thus eliminating quercetin efficiently from the body. The study shows that quercetin undergoes extensive first pass hepatic metabolism which in addition to the poor adsorption, means that quercetin has low bioavailability. Consequently, quercetin might be of limited therapeutic value, especially when taken orally. Whether or not the constant intake of quercetin via the diet may be beneficial to buttress the antioxidant defence system within the body remains to be elucidated.;The existence of GSH-conjugates of quercetin was investigated as a possible explanation for the nephrotoxicity exhibited in rats and the clinical trial. GSH-conjugates of quercetin were not found in vivo, although they could be synthesised in vitro.;Quercetin and isorhamnetin, although not quercetin sulphate nor glycosidic quercetin, exhibited potent COX-2 inhibition as demonstrated by reduced levels of PGE2 in HCA-7 cells.