Vascular deconjugation of quercetin glucuronide: The flavonoid paradox revealed?

Abstract

We propose that Q3GA behaves as a quercetin carrier in plasma, which deconjugates in situ releasing the aglycone which is the final effector.

Regulation of vascular endothelial genes by dietary flavonoids: structure-expression relationship studies and the role of the transcription factor KLF-2

“…This is due to the difficulty to obtain many commercial flavonoid conjugates. Nevertheless, recently it was postulated that orally administered quercetin, and probably other flavonoids, is conjugated in the intestine and liver to be transported bloodstream [31,32], and probably to be accumulated within diseased tissues [33], being the free flavonoid, released from its metabolite, the responsible for its activity.…”

The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: Correlation with beta-glucuronidase activity

“…In fact, these metabolites are usually less active than the parent aglycones and often totally inactive in vitro when tested for short periods of time [17]. However, the glucurono-conjugated metabolites of quercetin can be hydrolyzed by ␤-glucuronidase in several tissues, releasing the parent aglycone which accumulates intracellularly [18][19][20][21][22]. Therefore, at time periods longer than 1-2 h, Q3GA induces vasorelaxation in vitro [21] and reduces blood pressure in vivo [23] and both effects can be prevented by inhibition of ␤-glucuronidase.…”

Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

“…They were all found to be able to bind to the active site, but in a different orientation to the aglycones, with the conjugated moiety pointing towards the extracellular surface of the receptor (see Figure 6), suggesting that the activity of the compounds studied may be modified in vivo. However, there is also evidence that glucuronoconjugated metabolites of flavonoids are hydrolysed by β-glucuronidase, releasing the parent aglycone [37][38][39][40]. Hence further in vivo studies should be carried out to determine the usefulness of compounds which have been found to have good activity in vitro.…”