title: Receptor binding and transactivation activities of red clover isoflavones and their metabolites.
abstract: Red clover extracts contain a variety of isoflavones, which have affinity toward estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), androgen receptor (AR), and progesterone receptor (PR). Upon ingestion, they undergo various metabolic transformations. For a complete evaluation of red clover extracts and possible health benefits, the resulting metabolites should also be investigated. Biochanin A, formononetin, genistein, daidzein, dihydrobiochanin A, dihydroformononetin, dihydrogenistein, dihydrodaidzein, 3'-hydroxygenistein, 6-hydroxydaidzein, 6-hydroxydesmethylangolensin, equol, O-desmethylangolensin, angolensin, and p-ethylphenol were tested for their transactivation potential toward ERalpha, AR, and PR in yeast. Competitive binding assays with radiolabeled 17beta-estradiol, 17alpha-methyltrienolone or progesterone assessed binding to the respective ERalpha and ERbeta, AR, and PR. The compounds showed only weak binding affinity to AR and PR, with IC(50) values being greater (i.e., lesser affinity) than 10(-5)M for the respective receptor. So far, beneficial health effects have been attributed to the production of equol. We propose that other metabolites can also contribute to these effects. However, more detailed information for the formation of these metabolites in humans and for bioavailability data are required to confirm our assumptions.
authors.affiliation: Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Pfitscher
authors.forename: Evelyne
authors.initials: E
authors.lastname: Reiter
authors.forename: Alois
authors.initials: A
authors.lastname: Jungbauer
mesh_terms: D000728:Androgens; D001667:Binding, Competitive; D060754:Equol; D006801:Humans; D007529:Isoflavones / Q000378:metabolism* / Q000494:pharmacology; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism; D011980:Receptors, Progesterone / Q000819:agonists / Q000378:metabolism; D015533:Transcriptional Activation; D029921:Trifolium / Q000737:chemistry*; D015003:Yeasts / Q000378:metabolism
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D000728:Androgens; D007529:Isoflavones; D010936:Plant Extracts; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D060754:Equol