The complex degradation and metabolism of quercetin in rat hepatocyte incubations

Abstract

Abstract1. The current study demonstrated that there is still new information to be obtained on the chemical and biological transformation of the widely studied flavonoid quercetin.2. In rat hepatocytes thirty five metabolites of quercetin were observed by using high resolution mass spectrometry. The metabolites included glucuronides, sulphates, mixed sulphate/glucuronide metabolites and methylated versions of these metabolites.3. Several metabolites were formed from chemical degradation products of quercetin which were found to form in Krebs-Henseleit (KH) buffer, degradants of quercetin were also formed in the buffer under the conditions used for hepatocyte incubations.4. The degradants and metabolites of quercetin were characterised by using high resolution MS 2 . It was observed that the glutathione (GSH) conjugates of quercetin formed in large amounts in ammonium bicarbonate solution although the pattern of conjugates formed was different from that observed in hepatocytes suggesting some degree on enzymatic control on GSH conjugate formation in the hepatocyte incubations.5. GSH conjugates were not formed when GSH was included in incubations of quercetin in KH buffer alone and only small amounts of quercetin degradation occurred. Instead GSH was extensively converted into GSSG thus presumably reducing the levels of oxygen in the incubation thus preventing quercetin degradation.

Quercetin affects glutathione levels and redox ratio in human aortic endothelial cells not through oxidation but formation and cellular export of quercetin-glutathione conjugates and upregulation of glutamate-cysteine ligase

“…Quercetin-glutathione conjugates have been found in several cell types upon incubation with quercetin [23], [30], but have never been identified in endothelial cells. To investigate whether quercetin-glutathione conjugates are formed in HAEC during quercetin treatment, cells were incubated with 20 µM quercetin for 12 h. Glutathionyl conjugates of quercetin in cell extracts and the culture medium were identified by LC-MS, using synthetic quercetin-glutathione conjugates as standard.…”

Quercetin‐3‐glucoside increases low‐density lipoprotein receptor (LDLR) expression, attenuates proprotein convertase subtilisin/kexin 9 (PCSK9) secretion, and stimulates LDL uptake by Huh7 human hepatocytes in culture

“…In enterocytes, quercetin is largely metabolized to glucuronidated and/or methylated forms which are released into the bloodstream and taken up by multiple tissues, including the liver [46,47]. Quercetin uptake and metabolism by hepatocytes ex vivo have been studied [48]. A similar study for Q3G remains to be conducted.…”

Quercetin as an Emerging Anti-Melanoma Agent: A Four-Focus Area Therapeutic Development Strategy

“…The most commonly observed metabolites in circulation involve conjugation with glucuronides and/or sulfates, and methylated forms of these metabolites. Glutathione conjugates have also been observed but are likely restricted to enzymatic activity in the liver (62). It is, however, important to consider what role cellular effects of these conjugates play, and how it may differ from pure quercetin is an important question.…”