Kaempferol is an estrogen-related receptor alpha and gamma inverse agonist.
Kaempferol is a dietary flavonoid that is thought to function as a selective estrogen receptor modulator. In this study, we established that kaempferol also functions as an inverse agonist for estrogen-related receptors alpha and gamma (ERRalpha and ERRgamma). We demonstrated that kaempferol binds to ERRalpha and ERRgamma and blocks their interaction with coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). Kaempferol also suppressed the expressions of ERR-target genes pyruvate dehydrogenase kinase 2 and 4 (PDK2 and PDK4). This evidence suggests that kaempferol may exert some of its biological effect through both estrogen receptors and estrogen-related receptors.
Wang
Junjian
J
Center of Integrative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, China.
Fang
Fang
F
Huang
Zhiyan
Z
Wang
Yanfei
Y
Wong
Chiwai
C
D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D044949:Kaempferols / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics; D049410:Luciferases, Renilla / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics; D010957:Plasmids; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011960:Receptors, Estrogen / Q000819:agonists* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000097983:ERRalpha Estrogen-Related Receptor
D044949:Kaempferols; D049410:Luciferases, Renilla; D047495:PPAR gamma; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D000097983:ERRalpha Estrogen-Related Receptor; C490917:ESRRG protein, human; C000631430:PDK2 protein, human; C000631432:PDK4 protein, human; C006552:kaempferol