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 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.
Huang
Zhiyan
Z
Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Science City, China.
Fang
Fang
F
Wang
Junjian
J
Wong
Chi-Wai
CW
D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006569:Hesperidin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
C490917:ESRRG protein, human; D044950:Flavanones; D005419:Flavonoids; D006360:Heat-Shock Proteins; D007529:Isoflavones; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D014157:Transcription Factors; C004742:daidzein; D047310:Apigenin; D019833:Genistein; D006569:Hesperidin; C005273:naringenin; D047311:Luteolin; C013015:hesperetin