Kaempferol is an estrogen-related receptor α and γ 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 (ERR alpha and ERR gamma). We demonstrated that kaempferol binds to ERR alpha and ERR gamma and blocks their interaction with coactivator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha). 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. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.