Structural activity relationship of flavonoids with estrogen-related receptor gamma

In this study, we investigated the structural activity relationships (SARs) of flavonoids with estrogen-related receptor γ (ERRγ) and its coactivator peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α). Isoflavones (genistein and daidzein) and flavanones (naringenin and hesperetin) did not significantly affect ERRγ activity. Flavone apigenin and flavonol kaempferol directly suppressed the interaction between ERRγ and PGC-1α functioning as inverse agonists. In contrast, flavone luteolin suppressed PGC-1α activity in part through promoting the degradation of PGC-1α leading to suppressed ERRγ activity. Therefore, these flavones and flavonols utilize alternative mechanisms to influence the transcriptional activities of ERRγ and PGC-1α.Structured summaryMINT-7297297, MINT-7297435: PGC-1 alpha NR2 (uniprotkb:Q9UBK2) binds (MI:0407) to ERR gamma (uniprotkb:P62508) by surface plasmon resonance (MI:0107)