Department of Medicinal Chemistry and Pharmacognosy and Center for Biomolecular Sciences, College of Pharmacy , University of Illinois at Chicago , 833 S. Wood Street , Chicago , Illinois 60612 , United States.
J Nat Prod. 2018 Sep 28;81(9):1962-1967. doi: 10.1021/acs.jnatprod.8b00131. Epub 2018 Sep 10.
The use of botanical dietary supplements is becoming increasingly popular for the alleviation of hormonal-based conditions such as hot flashes, premenstrual syndrome, and fertility. Estrogen and progesterone receptors (ER and PR) play an essential role in these processes. However, despite the fact that many therapies used to alleviate gynecological conditions act through PR-mediated mechanisms, few studies have investigated or identified any herbal natural product components that act on this receptor. In the current study, we used a progesterone response element (PRE)-luciferase (Luc) reporter assay to identify four phytoprogestins present in a standardized red clover ( Trifolium pratense) extract. We found that the component irilone (1) potentiated the effect of progesterone in both endometrial and ovarian cancer cell lines. In these cancers, progesterone action is generally associated with positive outcomes; thus the potentiating effect of 1 may provide entirely new strategies for enhancing progesterone signaling as a means of mitigating conditions such as fibroids and endometriosis. Formononetin (3) and biochanin A (4) exhibited mixed agonist activity, while prunetin (2) acted only as an antagonist. Collectively, these results suggest that the effects of red clover extract repeatedly observed in cultured cells and the inverse correlation between risk of various cancers and flavonoid intake may be due, in part, to altered progesterone signaling.
植物性膳食补充剂的使用越来越流行，用于缓解与激素相关的疾病，如热潮红、经前期综合征和生育能力。雌激素和孕激素受体（ER 和 PR）在这些过程中起着至关重要的作用。然而，尽管许多用于缓解妇科疾病的疗法通过 PR 介导的机制发挥作用，但很少有研究调查或确定任何作用于该受体的草药天然产物成分。在当前的研究中，我们使用孕激素反应元件（PRE）-荧光素酶（Luc）报告基因检测法来鉴定标准化红三叶草（ Trifolium pratense ）提取物中存在的四种植物孕激素。我们发现，成分伊尔酮（1）增强了孕激素在子宫内膜癌和卵巢癌细胞系中的作用。在这些癌症中，孕激素的作用通常与良好的结果相关；因此，1 的增强作用可能为增强孕激素信号提供全新的策略，从而减轻子宫肌瘤和子宫内膜异位症等疾病。芒柄花素（3）和大豆苷元 A（4）表现出混合激动剂活性，而紫檀芪（2）仅作为拮抗剂。总的来说，这些结果表明，红三叶草提取物在培养细胞中反复观察到的作用以及各种癌症风险与类黄酮摄入之间的反比关系可能部分归因于孕激素信号的改变。
