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  • Title: Evaluation of endocrine activities of ellagic acid and urolithins using reporter gene assays.
    Author: Gramec Skledar D, Tomašič T, Sollner Dolenc M, Peterlin Mašič L, Zega A.
    Journal: Chemosphere; 2019 Apr; 220():706-713. PubMed ID: 30611068.
    Abstract:
    Urolithins are metabolites produced in the gut following consumption of ellagitannins and ellagic-acid-rich food, such as pomegranates, berries, and nuts. Compelling biological activities of urolithins together with variabilities between individuals in the metabolic capacity of the resident gut microbiota to produce urolithins, have suggested potential benefits of direct consumption of urolithins. Based on the structures of ellagic acid and urolithins, they might be expected to show endocrine effects. We report on their impact on the estrogen, androgen, glucocorticoid and thyroid-hormone receptors, as determined in vitro using reporter gene assays in the Hela9903 (estrogen receptor), MDA-kb2 (androgen and glucocorticoid receptors) and GH3.TRE-Luc (thyroid hormone receptor) cell lines. Urolithins A and B, but not ellagic acid and urolithin D, showed estrogenic activities on estrogen receptor subtype α under our assay conditions, with EC50 values of 5.59 μM and 32.60 μM, respectively. Moreover, ellagic acid and urolithins A and D showed anti-thyroid hormonal activities (IC50 values of 37.45 μM, 30.32 μM and 8.80 μM, respectively). Glucocorticoid and androgen agonist and antagonist activities were assessed using a luciferase reporter gene assay in the MDA-kb2 cell line. None of these tested compounds showed glucocorticoid agonist or antagonist activities, and ellagic acid showed weak androgen agonist activity, although only at the highest concentration tested. Detected estrogen and antithyroid activities warrant further risk assessment in relation to the exposure of urolithins in humans.
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