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.
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ABSTRACT: This study investigated the effects of perinatal genistein (GEN) exposure on the central nervous system of rat offspring. Pregnant dams orally received GEN (1 or 10mg/kg/day) or vehicle (1ml/kg/day) from gestation day 10 to postnatal day 14. In order to assess the effects of GEN on rat offspring, we used a battery of behavioral tests, including the open-field, elevated plus-maze, MAZE and step-though passive avoidance tests. MAZE test is an appetite-motivation test, and we used this mainly for assessing spatial learning and memory. In the MAZE test, GEN groups exhibited shorter latency from start to goal than the vehicle-treated group in both sexes. On the other hand, performances in the step-though passive avoidance test were non-monotonically inhibited by GEN in both sexes, and a significant difference was observed in low dose of the GEN-treated group compared to the vehicle-treated group in female rats. Furthermore, we found that perinatal exposure to GEN did not significantly alter locomotor activity or emotionality assessed by the open-field and elevated-plus maze tests. These results suggest that perinatal exposure to GEN improved spatial learning and memory of rat offspring, but impaired their passive avoidance learning and memory.Physiology & Behavior 03/2014; · 3.16 Impact Factor
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ABSTRACT: Background/objectives:Studies have observed associations between the gut microbiome and obesity. O-desmethylangolensin (ODMA) and equol are gut bacterial metabolites of daidzein, a compound found in high amounts in soy foods. Approximately 80-95% and 25-60% of individuals harbor gut microbial communities capable of producing ODMA or equol, respectively. Given that other phenotypes of gut bacterial metabolism of dietary compounds have been associated with obesity, we hypothesized that daidzein-metabolizing phenotypes would be associated with obesity. The objective of this study was to compare the prevalence of ODMA-producer and equol-producer phenotypes in obese, overweight and normal-weight individuals.Subjects/methods:Adults aged 18-95 years (n=297) provided a first-void urine sample after a 3-day soy challenge, and urinary ODMA and equol concentrations were used to classify individuals as producers or non-producers. Body mass index was calculated from self-reported weight and height.Results:There were 60 ODMA non-producers and 173 equol non-producers. Obese individuals were 2.8 times more likely to be ODMA non-producers (odds ratio (OR)=2.8, 95% confidence interval (CI): 1.2, 6.2) compared with normal-weight individuals, when adjusted for age, race (white vs non-white), and gender and menopausal status (male, premenopausal female and postmenopausal female). Obesity was not associated with equol-producer phenotype (OR=1.1, 95% CI: 0.5, 2.2). Stronger associations with obesity were observed in the ODMA non-producers who were also equol producers than in the equol non-producers.Conclusions:Results from this analysis suggest that the ODMA-producer phenotype, but not equol-producer phenotype, is associated with obesity in adults. These results support further work to replicate these findings and evaluate the mechanisms of the observed associations.European Journal of Clinical Nutrition advance online publication, 26 February 2014; doi:10.1038/ejcn.2014.23.European journal of clinical nutrition 02/2014; · 3.07 Impact Factor
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ABSTRACT: Phytoestrogens, phthalates, and phenols are estrogen-disrupting chemicals that have a pronounced effect at puberty. They are exogenous chemicals that are either plant-derived or man-made, and can alter the functions of the endocrine system and cause various health defects by interfering with the synthesis, metabolism, binding, or cellular responses of natural estrogens. Phytoestrogens, phthalates, and phenols are some of the potent estrogens detectable in urine. Phytoestrogens are plant-derived xenestrogens found in a wide variety of food products, like soy-based food, beverages, several fruits, and vegetables. Exposure to phytoestrogens can delay breast development and further lead to precocious puberty. The effect of phytoestrogens is mediated through estrogen receptors α and β or by binding with early immediate genes, such as jun and fos. Phthalates are multifunctional synthetic chemicals used in plastics, polyvinyl chloride products, cosmetics, hair spray, and children's toys. Phthalates have been shown to cause defeminization, thelarche, precocious puberty, and an increase in breast and pubic hair in pubertal girls. However, reports are also available that show no association of phthalates with precocious puberty in girls. Phthalates can act through a receptor-mediated signaling pathway or affect the production of luteinizing hormone and follicle-stimulating hormone that has a direct effect on estrogen formation. Phenols like bisphenol A are industrial chemicals used mainly in the manufacture of polycarbonates and plastic materials. Bisphenol A has been shown to cause precocious puberty and earlier menarche in pubertal girls. Reports suggest that the neurotoxic effect of bisphenol A can be mediated either by competing with estradiol for binding with estrogen receptors or via the ERK/NK-kappa or ERRγ pathway. This review demonstrates the effects of phytoestrogens, phthalates, and phenols on the development of girls during puberty.Adolescent Health, Medicine and Therapeutics 01/2012; 3:17-26.