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Nevertheless, the potential health-promoting effects of
flavonoids, based on their antioxidant properties, have recently
been challenged because flavonoids are extensively metabolized
and their metabolites are present in the plasma in small con-
centrations. Identification of circulating metabolites has been
undertaken for only a few flavonoids and those studies have
shownthatthecirculatingformofmostflavonoidsisasconjugates,
mainly as glucuronides.[42] Quercetin is the best characterized, and
the major circulating compounds found in rat plasma[29,43] and
human plasma[44,45] were identified as quercetin 3-O-glucuronide,
3ꢁ-O-methylquercetin 3-glucuronide and quercetin 3ꢁ-O-sulfate.
The conjugation reactions described above will not have to hin-
der the bromination of metabolites on the A-ring at C6 and C8
positions. In addition, glucuronides derivatives could serve as
transport metabolites to target cells, due to their low protein bind-
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more easily. Inside the cells, however, they can be hydrolized by
β –glucuronidase present in the lysosomes, from which it can be
released in some particular conditions, such as inflammation,[42]
and therefore to exert their effects.
It must be highlighted that besides the changes originated
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metabolites may also interact with signaling cascades involving
cytokines and regulatory transcription factors thus playing a role
on inflammation and in the regulation of immune response.[46]
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