New Evaluation of Isoflavone Exposure in the French Population

International audienceThe study relates the present evaluation of exposure to estrogenic isoflavones of French consumers through two approaches: (1) identification of the isoflavone sources in the French food offering, (2) a consumption-survey on premenopausal women. For the foodstuff approach 150 food-items were analysed for genistein and daidzein. Additionally, 12,707 labels of processed-foods from French supermarket websites and a restaurant-supplier website were screened, and 1616 foodstuffs of interest were retained. The sources of phytoestrogens considered were soy, pea, broad bean and lupine. A price analysis was performed. A total of 270 premenopausal women from the French metropolitan territory were interviewed for their global diet habits and soy consumption and perception. In supermarkets, there were significantly less selected foodstuffs containing soy than in restaurant (11.76% vs 25.71%, p 45 mg/day is associated to vegan-diet (p 50 mg/day. This dose can lengthen the menstrual cycles. The actual exposure to phytoestrogen is likely to have an effect in a part of the French population

Comparative Effects of R- and S-equol and Implication of Transactivation Functions (AF-1 and AF-2) in Estrogen Receptor-Induced Transcriptional Activity

Equol, one of the main metabolites of daidzein, is a chiral compound with pleiotropic effects on cellular signaling. This property may induce activation/inhibition of the estrogen receptors (ER) a or b, and therefore, explain the beneficial/deleterious effects of equol on estrogen-dependent diseases. With its asymmetric centre at position C-3, equol can exist in two enantiomeric forms (R- and S-equol). To elucidate the yet unclear mechanisms of ER activation/inhibition by equol, we performed a comprehensive analysis of ERa and ERb transactivation by racemic equol, as well as by enantiomerically pure forms. Racemic equol was prepared by catalytic hydrogenation from daidzein and separated into enantiomers by chiral HPLC. The configuration assignment was performed by optical rotatory power measurements. The ER-induced transactivation by R- and S-equol (0.1–10 µM) and 17b-estradiol (E2, 10 nM) was studied using transient transfections of ERα and ERβ in CHO, HepG2 and HeLa cell lines. R- and S-equol induce ER transactivation in an opposite fashion according to the cellular context. R-equol and S-equol are more potent in inducing ERα in an AF-2 and AF-1 permissive cell line, respectively. Involvement of ERα transactivation functions (AF-1 and AF-2) in these effects has been examined. Both AF-1 and AF-2 are involved in racemic equol, R-equol and S-equol induced ERα transcriptional activity. These results could be of interest to find a specific ligand modulating ER transactivation and could contribute to explaining the diversity of equol actions in vivo

Phytomicronutriments et pathologies oculaires

National audienc

Phytoestrogens and Health Effects

Phytoestrogens are literally estrogenic substances of plant origin. Although these substances are useful for plants in many aspects, their estrogenic properties are essentially relevant to their predators. As such, phytoestrogens can be considered to be substances potentially dedicated to plant–predator interaction. Therefore, it is not surprising to note that the word phytoestrogen comes from the early discovery of estrogenic effects in grazing animals and humans. Here, several compounds whose activities have been discovered at nutritional concentrations in animals and humans are examined. The substances analyzed belong to several chemical families, i.e., the flavanones, the coumestans, the resorcylic acid lactones, the isoflavones, and the enterolignans. Following their definition and the evocation of their role in plants, their metabolic transformations and bioavailabilities are discussed. A point is then made regarding their health effects, which can either be beneficial or adverse depending on the subject studied, the sex, the age, and the physiological status. Toxicological information is given based on official data. The effects are first presented in humans. Animal models are evoked when no data are available in humans. The effects are presented with a constant reference to doses and plausible exposure

Phytoestrogens and Health Effects

International audiencePhytoestrogens are literally estrogenic substances of plant origin. Although these substances are useful for plants in many aspects, their estrogenic properties are essentially relevant to their predators. As such, phytoestrogens can be considered to be substances potentially dedicated to plant–predator interaction. Therefore, it is not surprising to note that the word phytoestrogen comes from the early discovery of estrogenic effects in grazing animals and humans. Here, several compounds whose activities have been discovered at nutritional concentrations in animals and humans are examined. The substances analyzed belong to several chemical families, i.e., the flavanones, the coumestans, the resorcylic acid lactones, the isoflavones, and the enterolignans. Following their definition and the evocation of their role in plants, their metabolic transformations and bioavailabilities are discussed. A point is then made regarding their health effects, which can either be beneficial or adverse depending on the subject studied, the sex, the age, and the physiological status. Toxicological information is given based on official data. The effects are first presented in humans. Animal models are evoked when no data are available in humans. The effects are presented with a constant reference to doses and plausible exposure.Les phyto-œstrogènes sont littéralement des substances oestrogéniques d'origine végétale. Bien que ces substances soient utiles pour les plantes à bien des égards, leurs propriétés oestrogéniques concernent essentiellement leurs prédateurs. A ce titre, les phyto-œstrogènes peuvent être considérés comme des substances potentiellement dédiées à l'interaction plante-prédateur. Par conséquent, il est intéressant de surprenant de noter que le mot phyto-œstrogène provient de la découverte précoce d'effets œstrogéniques chez les animaux de pâturage et les humains. Ici, plusieurs composés dont les activités ont été découvertes à des concentrations nutritionnelles chez les animaux et les humains sont examinés. Les substances analysées appartiennent à plusieurs familles chimiques, à savoir les flavanones, les coumestans, les lactones résorcyliques, les isoflavones et les entérolignanes. Après leur définition et l'évocation de leur rôle chez les plantes, leurs transformations métaboliques et leurs biodisponibilités sont discutées. Un point est ensuite fait sur leurs effets sur la santé, qui peuvent être bénéfiques ou néfastes selon le sujet étudié, le sexe, l'âge et l'état physiologique. Les informations toxicologiques sont données sur la base des données officielles. Les effets sont d'abord présentés chez l'homme. Les modèles animaux sont évoqués lorsqu'aucune donnée n'est disponible chez l'homme. Les effets sont présentés avec une référence constante aux doses et à l'exposition plausible

Enterodiol and enterolactone, two major diet-derived polyphenol metabolites have different impact on ERalpha transcriptional activation in human breast cancer cells.

International audienceLignans are plant compounds metabolized in the mammalian gut to produce the estrogenic enterolignans, enterodiol (ED) and enterolactone (EL). Because estrogens have been linked to breast cancer etiology, enterolignans could affect breast cancer risk, but to our knowledge, the mechanisms by which they exert their estrogenic and/or anti-estrogenic effects in humans are still unclear. To better understand how estrogenic compounds from the food, such as the enterolignans, might influence breast cancer progression and their mechanisms to interfere with human estrogen receptor (ER) signalling in hormone-dependant diseases, we examined and compared the ability of ED, EL and 17beta-estradiol (E2) to induce the transactivation of ERalpha and ERbeta, to modulate ERalpha target genes, to exert either growth stimulatory or anti-proliferative effects and finally to modulate MCF-7 cell migration by acting on matrix metalloproteases (MMP)-2 and -9, at concentrations that are achievable through a lignan-rich diet. This study indicates that enterolignans show distinct properties for transactivation of ERalpha and ERbeta. ED, as E2, induces ERalpha transcriptional activation through transactivation functions AF-1 and AF-2, while EL is less efficient in inducing AF-1, acting predominantly through AF-2. Furthermore, ED and EL modulate ERalpha mRNA and protein contents as well as MCF-7 cell proliferation and secreted MMP activities in a different way. Enterolignans are compounds of wide interest nowadays and our results help to unveil their mechanisms of action on ER, emphasizing the fact that the dietary load in lignans could be of importance in the balance between being risk or chemopreventive factors for breast cancer and women's health

Risks and safety of polyphenol consumption

National audienceThis article gives an overview of the potential hazards of polyphenol consumption, as reported during the round-table discussion at the 1st International Conference on Polyphenols and Health, held in Vichy, France, November 2003. Adverse effects of polyphenols have been evaluated primarily in experimental studies. It is known, for example, that certain polyphenols may have carcinogenic/genotoxic effects or may interfere with thyroid hormone biosynthesis. Isoflavones are of particular interest because of their estrogenic activity, for which beneficial as well as detrimental effects have been observed. Furthermore, consumption of polyphenols inhibits nonheme iron absorption and may lead to iron depletion in populations with marginal iron stores. Finally, polyphenols may interact with certain pharmaceutical agents and enhance their biologic effects. It is important to consider the doses at which these effects occur, in relation to the concentrations that naturally occur in the human body. Future studies evaluating either beneficial or adverse effects should therefore include relevant forms and doses of polyphenols and, before the development of fortified foods or supplements with pharmacologic doses, safety assessments of the applied doses should be performed

Respective contribution exerted by AF-1 and AF-2 transactivation functions in estrogen receptor alpha induced transcriptional activity by isoflavones and equol: consequence on breast cancer cell proliferation.

International audienceEstrogens used in hormone replacement therapy regimens may increase the risk of developing breast cancer. Paradoxically, high consumption of plant-derived phytoestrogens, particularly soybean isoflavones, is associated with a low incidence of breast cancer. To explore the molecular basis for these potentially different experimental/clinical outcomes, we investigated whether soybean isoflavones elicit distinct transcriptional actions from estrogens by performing transient transfections in different cell lines. Our results demonstrate that 17beta estradiol (E2), isoflavones, and equol (EQ) effectively trigger the transcriptional activation with both estrogen receptors (ER), ER alpha and ER beta. ER alpha transcriptional activity is mediated through two transactivation domains AF-1 and AF-2, whose activity is tightly regulated in a cell-type and promoter-specific manner. Isoflavones, genistein, and daidzein (DAI), and EQ, the main estrogenic metabolite of DAI, are ER alpha agonists for transcriptional activation. The molecular mechanisms for ER alpha-induced transcriptional activity by isoflavones and EQ involve their capacity to act mainly through AF-1 regardless of the cell type. Therefore, our data indicate that estrogenic ligands, such as isoflavones and EQ, exert their effects on ER alpha transactivation similarly to the endogenous ligand E2, and suggest that the risk of estrogen-related diseases might not be reduced by soy-rich food and/or isoflavone- or EQ-based supplements

When dietary supplements meet metabolomics: A fast-evolving field—A follow-up of ABR volume 67: Metabolomics coming of age with its technological diversity

Volume 67 of Advances in Botanical Research "Metabolomics coming of age with its technological diversity" edited by Dominique Rolin (series Editors Jean-Pierre Jacquot and Pierre Gadal) was published in 2013 and featured 13 chapters including more than 40 authors with a range of expertise in biology, biochemistry, analytical chemistry, chemometrics and bioinformatics. This volume highlighted the technological diversity of metabolomics approaches that have revolutionized life sciences, more particularly plant biology, providing a deeper understanding of the multifaceted chemical and physiological variety of plant systems. Since its initiation, metabolomics has never failed to deliver further progress in research fields. In this anniversary volume 100 of ABR, a special focus is placed on the contribution of metabolomics to the study of dietary supplements, where Chemistry, Botanics and Physiology cross path. We also highlight the current challenges and future perspectives in this inspiring, fast-evolving area, which holds great promise for unraveling novel mechanisms by which food supplements benefit Human nutrition and health