Abstract
Flavonoids are a large class of dietary molecules, among which quercetin is the most ubiquitous, which undergo an extensive intestinal phase-II metabolism. We compared the in vivo metabolism of quercetin in healthy volunteers with two in vitro models, HT29 cells and 3 D human intestinal tissues. Supernatants of the in vitro experiments and the human intestinal fluids (HIF) were analyzed by LC-IMS-MS and LC-HRMS in a qualitative way.
Quercetin glucuronides, sulfates and their methyl conjugates were detected in all three systems. The metabolic profiles were found to be different, both in terms of the metabolites produced and their relative proportions. In particular, quercetin sulfates were almost absent in supernatants from HT29 cells incubations while they were a major metabolite in HIF and also found in 3 D intestinal tissues incubations.
IMS provided structural information as well as a third dimension of characterization, while HRMS brought increased sensitivity and MS/MS confirmation. HT29 cells are a useful tool to generate phase-II metabolites but do not represent the in vivo situation. 3 D intestinal tissues appear as a more relevant tool to study the intestinal phase-II metabolism of flavonoids.
Acknowledgements
This work was supported by ARIADME, a European FP7 ITN Community's Seventh Framework program under Grant Agreement No. 607517. The authors wish to acknowledge Hans-Gerd Janssen for the helpful discussions on the analytical issues, Jari Rubbens and Jan Tack for their precious assistance with the clinical study and Paul Oranje for his help with the 3D human intestinal tissues.
Disclosure statement
C.C., B.H. and G.D. are or were at the time employed by Unilever, which markets quercetin-containing products such as green tea. The authors report no declarations of interest.