University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA.
PLoS One. 2013 Jul 12;8(7):e67947. doi: 10.1371/journal.pone.0067947. Print 2013.
The increased cancer risk associated with hormone therapies has encouraged many women to seek non-hormonal alternatives including botanical supplements such as hops (Humulus lupulus) and licorice (Glycyrrhiza spec.) to manage menopausal symptoms. Previous studies have shown estrogenic properties for hops, likely due to the presence of 8-prenylnarigenin, and chemopreventive effects mainly attributed to xanthohumol. Similarly, a combination of estrogenic and chemopreventive properties has been reported for various Glycyrrhiza species. The major goal of the current study was to evaluate the potential estrogenic effects of three licorice species (Glycyrrhiza glabra, G. uralensis, and G. inflata) in comparison with hops. Extracts of Glycyrrhiza species and spent hops induced estrogen responsive alkaline phosphatase activity in endometrial cancer cells, estrogen responsive element (ERE)-luciferase in MCF-7 cells, and Tff1 mRNA in T47D cells. The estrogenic activity decreased in the order H. lupulus > G. uralensis > G. inflata > G. glabra. Liquiritigenin was found to be the principle phytoestrogen of the licorice extracts; however, it exhibited lower estrogenic effects compared to 8-prenylnaringenin in functional assays. Isoliquiritigenin, the precursor chalcone of liquiritigenin, demonstrated significant estrogenic activities while xanthohumol, a metabolic precursor of 8-prenylnaringenin, was not estrogenic. Liquiritigenin showed ERβ selectivity in competitive binding assay and isoliquiritigenin was equipotent for ER subtypes. The estrogenic activity of isoliquiritigenin could be the result of its cyclization to liquiritigenin under physiological conditions. 8-Prenylnaringenin had nanomolar estrogenic potency without ER selectivity while xanthohumol did not bind ERs. These data demonstrated that Glycyrrhiza species with different contents of liquiritigenin have various levels of estrogenic activities, suggesting the importance of precise labeling of botanical supplements. Although hops shows strong estrogenic properties via ERα, licorice might have different estrogenic activities due to its ERβ selectivity, partial estrogen agonist activity, and non-enzymatic conversion of isoliquiritigenin to liquiritigenin.
与激素疗法相关的癌症风险增加促使许多女性寻求非激素替代疗法，包括植物补充剂，如啤酒花（Humulus lupulus）和甘草（Glycyrrhiza spec.），以缓解更年期症状。先前的研究表明啤酒花具有雌激素特性，可能是由于存在 8-prenylnarigenin，并且具有化学预防作用主要归因于黄腐酚。类似地，各种甘草属植物被报道具有雌激素和化学预防特性的组合。当前研究的主要目标是评估三种甘草属植物（甘草、甘草和甘草）与啤酒花相比的潜在雌激素作用。甘草属植物提取物和用过的啤酒花诱导子宫内膜癌细胞中的雌激素反应性碱性磷酸酶活性、MCF-7 细胞中的雌激素反应元件（ERE）-荧光素酶和 T47D 细胞中的 Tff1 mRNA。雌激素活性按 H. lupulus > G. uralensis > G. inflata > G. glabra 的顺序降低。在功能测定中，发现甘草提取物中的主要植物雌激素是甘草素；然而，与 8-prenylnaringenin 相比，它表现出较低的雌激素作用。异甘草素，甘草素的前体查尔酮，表现出显著的雌激素活性，而黄腐酚，8-prenylnaringenin 的代谢前体，没有雌激素活性。在竞争性结合测定中，甘草素显示出 ERβ选择性，而异甘草素对 ER 亚型具有同等效力。异甘草素的雌激素活性可能是其在生理条件下环化为甘草素的结果。8-prenylnaringenin 具有毫摩尔级的雌激素效力，没有 ER 选择性，而黄腐酚不与 ER 结合。这些数据表明，具有不同甘草素含量的甘草属植物具有不同水平的雌激素活性，这表明植物补充剂的精确标记非常重要。尽管啤酒花通过 ERα 表现出强烈的雌激素特性，但由于其 ERβ 选择性、部分雌激素激动剂活性以及异甘草素向甘草素的非酶转化，甘草可能具有不同的雌激素活性。
