Receptor binding and transactivation activities of red clover isoflavones and their metabolites

Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.
The Journal of Steroid Biochemistry and Molecular Biology (Impact Factor: 4.05). 10/2008; 112(1-3):87-94. DOI: 10.1016/j.jsbmb.2008.08.007
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Prostate cancer is the most frequently diagnosed form of cancer and the second leading cause of cancer related deaths in the United States. Increased consumption,of soy is thought to reduce the risk for this disease. More specifically, the isoflavones found in soy are responsible, in part, for these anticancer effects. Isoflavones are organic compounds found in soy and other legumes and it is thought that methylated isoflavones (glycitein, biochanin A, formononetin) may have greater anticancer activity than those without methyl groups (genistein, daidzein, equol). However, the majority of studies, to date, have focused primarily on the nonmethylated isoflavones, genistein and daidzein. Epidemiological evidence also suggests that the anticancer effects of soy may be greatest during the precancerous stages of prostate cancer. Few studies, however, have examined the impact of soy isoflavones during this precancerous stage. This study examined,the antiproliferative effects of methylated and nonmethylated,soy isoflavones using a precancerous prostate cell line (WPE1-NB14). The precancerous prostate cells were treated with the six different soy isoflavones, three methylated and three nonmethylated, in different concentrations (0-50µM). Cell viability was determined using the 3-[4,5- dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. This assay uses MTT to color the living cells in order to determine the cell viability. The results of this study suggest that methylated isoflavones reduced precancerous cell viability to a greater extent than nonmethylated,isoflavones and indicate that the methyl group does contribute to the anticancer effects of soy isoflavones in precancerous prostate cells. While most studies focus on nonmethylated isoflavones because they are the most abundant, they are not necessarily the most
  • [Show abstract] [Hide abstract]
    ABSTRACT: The isoflavones present in red clover and soy are used as an alternative treatment for menopausal complaints and are commercially available as high-dose food supplements. These preparations contain varying amounts of active ingredients, often without detailed specifications. Thus, it is difficult to derive a recommended daily dose, and the reliability of these products is rather low. We quantified the isoflavone content of 19 different isoflavone-containing preparations and compared their binding and transactivational activities with regard to estrogen receptor alpha, estrogen receptor beta, androgen receptor, progesterone receptor, peroxisome-proliferator-activated receptor, and aryl hydrocarbon receptor. The food supplements that we tested bound to and transactivated both the estrogen receptors and the other receptors. After comparing the isoflavone content quantified by us with the isoflavone content specified on the package labels, we found that at least the specified isoflavone content or more could be detected in only 5 of the 19 food supplements that we tested. Preparations containing isoflavones should be standardized for the isoflavone aglycone content to facilitate the prediction of theoretical hormonal activity, facilitate the intake of a controlled amount of isoflavones, and ensure greater product reliability.
    Menopause (New York, N.Y.) 06/2009; 16(5):1049-60. DOI:10.1097/gme.0b013e31819c146c · 2.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genistein has been implicated in the beneficial effects of soy on human health, particularly in the context of ageing. In post-menopausal women reduced systemic estrogen leads to a range of age-associated pathologies, including delayed cutaneous wound healing. We have previously shown that this can be reversed by estrogen replacement. However, the effect of genistein on the skin is poorly understood and crucially the influence of genistein on wound healing has not been assessed. 10-week-old ovariectomised mice were systemically treated with 17beta-estradiol or genistein. Genistein substantially accelerated wound repair, associated with a dampened inflammatory response. Unexpectedly, co-treatment with the ER antagonist ICI had little impact on the anti-inflammatory, healing promoting effects of genistein. Thus genistein's actions are only partially mediated via classical estrogen receptor-dependent signalling pathways. Indeed, we report that alternative (cell-type specific) signalling mechanisms are activated in the skin in response to genistein treatment.
    Molecular and Cellular Endocrinology 02/2010; 321(2):184-93. DOI:10.1016/j.mce.2010.02.026 · 4.24 Impact Factor
Show more