Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic model: the role of human β-glucuronidase, sulfotransferase, catechol-O-methyltransferase and multi-resistant protein 2 (MRP2) in flavonoid metabolism

Development of ionic-complex-based nanostructured lipid carriers to improve the pharmacokinetic profiles of breviscapine

“…β-Glucuronidase, which is highly expressed in the liver, is the main enzyme that is responsible for hydrolyzing a glucuronide conjugate [41] . Breviscapine could be hydrolyzed by β-glucuronidase into aglycone [42,43] , which would result in a fast decrease in the Bre-solution in the liver.…”

Inhibition of hydroxycinnamic acid sulfation by flavonoids and their conjugated metabolites

“…Moreover, flavonoids such as quercetin are highly metabolized in the intestine and are conjugated before reaching the liver [22]. Here, we demonstrate that glucuronide and sulfate conjugates of quercetin also significant inhibited sulfation in human liver S9, with IC 50 values in the low micromolar range.…”

“…However, given the low sulfatase activity in HepG2 cells [22], it is likely that quercetin -3′-O-sulfate act predominantly as a direct inhibitor of SULTs in these cells.…”

“…Indeed, we found that the uptake of quercetin-3′-O-sulfate was 8-fold greater than quercetin-3-O-glucuronide and quercetin-7-O-glucuronide in HepG2 cells (Figure 3). While quercetin-3-O-glucuonide and quercetin-7-O-glucuronide can be hydrolyzed, and re-conjugated in HepG2 cells to form quercetin-3′-O-sulfate [22], the rate of conversion is very low (<10 % after 48 h). Thus, the contribution of formed quercetin-3′-O-sulfate to cellular uptake and SULT-inhibitory effect of quercetin glucuronides is expected to be minimal over 4 h.…”

Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

“…These finding support that p38 MAPK plays a critical role in FEOJ-induced apoptosis. In addition, the merit of FEOJ as compared to the quercetin is that the bioavailability of quercetin in FEOJ is much better that that quercetin aglycone (Manach et al, 2005;Gibellini et al, 2011), because quercetin in FEOJ is in the form of quercetin glucosides, which are easily absorbed in the apical membrane of enterocyte (O'Leary et al, 2003).…”