The effect of quercetin and kaempferol aglycones and glucuronides on peroxisome proliferator-activated receptor-gamma (PPAR-γ)

Food & Function
Karsten BeekmannIvonne M C M Rietjens

Abstract

The consumption of dietary flavonoids has been associated with a variety of health benefits, including effects mediated by the activation of peroxisome proliferator-activated receptor-gamma (PPAR-γ). Flavonoids are extensively metabolized during and after uptake and there is little known on the biological effects of these conjugated metabolites of flavonoids that are found in plasma. To investigate the effect of glucuronidation on the ability of flavonoids to activate PPAR-γ we studied and compared the activity of quercetin, kaempferol and their relevant plasma conjugates quercetin-3-O-glucuronide (Q3G) and kaempferol-3-O-glucuronide (K3G) on different PPAR-γ related endpoints. The flavonoid aglycones increased PPAR-γ mediated gene expression in a stably transfected reporter gene cell line and glucuronidation diminished their effect. To study the intrinsic activity of the test compounds to activate PPAR-γ we used a novel microarray technique to study ligand induced ligand binding domain (LBD) - nuclear receptor coregulator interactions. In this cell-free system we demonstrate that, unlike the known PPAR-γ agonist rosiglitazone, neither the flavonoid aglycones nor the conjugates are agonistic ligands of the receptor. The increas...Continue Reading

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Citations

May 5, 2016·The Journal of Nutritional Biochemistry·Antonio Casado-DíazJosé Manuel Quesada-Gómez
Jun 5, 2016·The Journal of Nutritional Biochemistry·Cheng-Hung ChuangYing-Hsuna Wang
Feb 8, 2020·Journal of Cellular and Molecular Medicine·Liwei WuJianye Wu
Jan 6, 2021·Food & Function·Sakuka Tsukamoto-SenNobuharu L Fujii
May 17, 2021·European Journal of Medicinal Chemistry·Carlos Villarroel-VicenteNuria Cabedo

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