Agonistic and antagonistic estrogens in licorice root (Glycyrrhiza glabra) |
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Authors: | Simons Rudy Vincken Jean-Paul Mol Loes A M The Susan A M Bovee Toine F H Luijendijk Teus J C Verbruggen Marian A Gruppen Harry |
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Institution: | (1) Laboratory of Food Chemistry, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands;(2) Frutarom Netherlands BV, Landjuweel 5, 3905 PE Veenendaal, The Netherlands;(3) Department of Safety and Health, RIKILT-Institute of Food Safety, P.O. Box 230, 6700 AE Wageningen, The Netherlands;(4) PRISNA bv, Einsteinweg 55, 2333 CC Leiden, The Netherlands; |
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Abstract: | The roots of licorice (Glycyrrhiza glabra) are a rich source of flavonoids, in particular, prenylated flavonoids, such as the isoflavan glabridin and the isoflavene
glabrene. Fractionation of an ethyl acetate extract from licorice root by centrifugal partitioning chromatography yielded
51 fractions, which were characterized by liquid chromatography–mass spectrometry and screened for activity in yeast estrogen
bioassays. One third of the fractions displayed estrogenic activity towards either one or both estrogen receptors (ERs; ERα
and ERβ). Glabrene-rich fractions displayed an estrogenic response, predominantly to the ERα. Surprisingly, glabridin did
not exert agonistic activity to both ER subtypes. Several fractions displayed higher responses than the maximum response obtained
with the reference compound, the natural hormone 17β-estradiol (E2). The estrogenic activities of all fractions, including this so-called superinduction, were clearly ER-mediated, as the estrogenic
response was inhibited by 20–60% by known ER antagonists, and no activity was found in yeast cells that did not express the
ERα or ERβ subtype. Prolonged exposure of the yeast to the estrogenic fractions that showed superinduction did, contrary to
E2, not result in a decrease of the fluorescent response. Therefore, the superinduction was most likely the result of stabilization
of the ER, yeast-enhanced green fluorescent protein, or a combination of both. Most fractions displaying superinduction were
rich in flavonoids with single prenylation. Glabridin displayed ERα-selective antagonism, similar to the ERα-selective antagonist
RU 58668. Whereas glabridin was able to reduce the estrogenic response of E2 by approximately 80% at 6 × 10−6 M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERα. |
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