Structural activity relationship of flavonoids with estrogen‐related receptor gamma

Abstract

In this study, we investigated the structural activity relationships (SARs) of flavonoids with estrogen-related receptor gamma (ERRgamma) and its coactivator peroxisome proliferators-activated receptor gamma coactivator-1alpha (PGC-1alpha). Isoflavones (genistein and daidzein) and flavanones (naringenin and hesperetin) did not significantly affect ERRgamma activity. Flavone apigenin and flavonol kaempferol directly suppressed the interaction between ERRgamma and PGC-1alpha functioning as inverse agonists. In contrast, flavone luteolin suppressed PGC-1alpha activity in part through promoting the degradation of PGC-1alpha leading to suppressed ERRgamma activity. Therefore, these flavones and flavonols utilize alternative mechanisms to influence the transcriptional activities of ERRgamma and PGC-1alpha.