Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands.
Anal Bioanal Chem. 2011 Jul;401(1):305-13. doi: 10.1007/s00216-011-5061-9. Epub 2011 May 15.
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 (E(2)). 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 E(2), 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 E(2) by approximately 80% at 6 × 10(-6) M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERα.
甘草（Glycyrrhiza glabra）的根是类黄酮的丰富来源，特别是类异戊二烯黄酮，如异黄烷甘草素和异黄烷甘草素。通过离心分配色谱对甘草根的乙酸乙酯提取物进行分级分离，得到 51 个馏分，通过液相色谱-质谱对其进行了表征，并在酵母雌激素生物测定中筛选了其活性。三分之一的馏分对一种或两种雌激素受体（ER；ERα和 ERβ）具有雌激素活性。富含甘草素的馏分表现出雌激素反应，主要针对 ERα。令人惊讶的是，甘草素对两种 ER 亚型均没有激动活性。一些馏分的反应比参考化合物天然激素 17β-雌二醇（E(2)）的最大反应更高。所有馏分的雌激素活性，包括这种所谓的超诱导，都明显是通过 ER 介导的，因为雌激素反应被已知的 ER 拮抗剂抑制了 20-60%，并且在不表达 ERα 或 ERβ 亚型的酵母细胞中没有发现活性。与 E(2)相反，与超诱导相关的雌激素馏分延长暴露于酵母中，不会导致荧光反应减少。因此，超诱导很可能是 ER、酵母增强型绿色荧光蛋白或两者的稳定化的结果。显示超诱导的大多数馏分富含具有单萜烯化的类黄酮。甘草素显示出与 ERα 选择性拮抗剂 RU 58668 相似的 ERα 选择性拮抗作用。虽然甘草素在 6×10(-6) M 时能够将 E(2)的雌激素反应降低约 80%，但富含甘草素的馏分仅表现出激动活性，主要针对 ERα。
