title: The isoflavone irilone contributes to the estrogenic potential of dietary supplements containing red clover.
abstract: A recent intervention study demonstrated the occurrence of irilone as second most abundant isoflavone next to daidzein in human plasma after consumption of a red clover-based dietary supplement (RCDS) containing predominately formononetin ≫ biochanin A > irilone (12 % of these isoflavones). To elucidate the relevance of this finding, in the present study (1) the representativeness of the isoflavone composition of the RCDS and (2) the estrogenic activity of irilone were investigated. Thus, major isoflavones were quantified in eight commercially available RCDS. Furthermore, the estrogenic activities of irilone and other isoflavones were determined by marker gene expression in Ishikawa and cell proliferation in MCF-7 cells. Irilone amounted to 1.8-10.9 mg/g capsule content and 5-18 % of the three major isoflavones, respectively, demonstrating the general occurrence of irilone in RCDS. Moreover, irilone significantly induced the activity of alkaline phosphatase (AlP) as well as AlP, progesterone receptor, and androgen receptor mRNA levels in Ishikawa cells. Furthermore, irilone significantly induced MCF-7 cell proliferation. Neither 17β-estradiol (E2)-induced AlP activity nor E2-induced MCF-7 cell proliferation was affected by irilone. ICI182,780 antagonized IRI-induced effects on both AlP activity and cell proliferation, suggesting an estrogen receptor agonistic mode of action. Taking into account the estrogenic activity of red clover isoflavones (formononetin, biochanin A, prunetin, glycitein) and their biotransformation products (daidzein, genistein, ethylphenol) as well as published plasma levels of isoflavones after consumption of RCDS, irilone could contribute approximately 50 % of the E2 equivalents estimated for daidzein.
authors: Institute of Pharmacy and Food Chemistry, Chair of Food Chemistry, University of Wuerzburg, Am Hubland, 97074, Würzburg, Germany.
authors: Stefanie
authors: S
authors: Lutter
authors: Katja
authors: K
authors: Schmalbach
authors: Harald L
authors: HL
authors: Esch
authors: Leane
authors: L
authors: Lehmann
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019587:Dietary Supplements; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007529:Isoflavones / Q000032:analysis* / Q000494:pharmacology*; D061986:MCF-7 Cells / Q000187:drug effects; D011980:Receptors, Progesterone / Q000235:genetics; D029921:Trifolium / Q000737:chemistry*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D007529:Isoflavones; D011980:Receptors, Progesterone; C530234:irilone; D007041:Hypoxanthine Phosphoribosyltransferase; D000469:Alkaline Phosphatase