Egonol gentiobioside and egonol gentiotrioside from Styrax perkinsiae promote the biosynthesis of estrogen by aromatase
Egonol gentiobioside and egonol gentiotrioside from Styrax perkinsiae promote the biosynthesis of estrogen by aromatase
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苏合香中的乙醇龙胆二糖苷和乙醇龙胆三糖苷通过芳香酶促进雌激素的生物合成
DOI：
10.1016/j.ejphar.2012.07.005
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发表时间：
2012-09-15
影响因子：
5
通讯作者：
Zhang, Guolin
中科院分区：
文献类型：
--
作者：
Lu, Danfeng;Yang, Lijuan;Zhang, Guolin
雌激素缺乏与多种疾病有关，包括骨质疏松症、动脉粥样硬化和阿尔茨海默病。芳香酶细胞色素P450是脊椎动物中已知的唯一能催化雄激素合成雌激素的酶。芳香化酶抑制剂已被开发用于治疗雌激素依赖性乳腺癌。然而，很少报道芳香化酶的小分子激动剂，这将有助于局部促进雌激素的生物合成，以预防雌激素缺乏引起的疾病。本研究利用人卵巢颗粒KGN细胞建立了一种检测芳香化酶活性的非放射性方法，并鉴定了两种促进雌激素生物合成的化合物，即紫金Styrax perkinsiae中的egonol gentioioside和egonol gentiotrioside。这些化合物还促进了3T3-L1前脂肪细胞的雌激素生物合成。进一步的研究表明，这两种化合物都不影响KGN细胞中芳香化酶的转录和翻译表达，但都显著提高了重组表达的芳香化酶的体外酶活性。Egonol gentiotrioside也被发现可以提高去卵巢大鼠的血清雌激素水平。这些结果表明，这两种化合物可能通过对芳香化酶活性的变构调节来促进雌激素的生物合成。因此，Egonol gentiobioside和Egonol gentiotrioside是有价值的结构修饰靶点，值得进一步研究它们作为预防雌激素缺乏引起的疾病的新型药物工具的潜力。(c) 2012 Elsevier B.V.版权所有
Estrogen deficiency is associated with a variety of diseases, including osteoporosis, atherosclerosis, and Alzheimer's disease. Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyze the biosynthesis of estrogens from androgens. Inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer. However, small molecular agonists of aromatase, which would be useful to locally promote estrogen biosynthesis for the prevention of estrogen deficiency-induced diseases, are rarely reported. In this study, we established a nonradioactive assay for measuring aromatase activity by using human ovarian granulosa KGN cells and identified two estrogen biosynthesis-promoting compounds, egonol gentiobioside and egonol gentiotrioside from Styrax perkinsiae. The compounds also promoted estrogen biosynthesis in 3T3-L1 preadipocyte cells. Further study showed that neither compound affected the transcriptional and translational expression of aromatase in KGN cells, but that both significantly promoted the in vitro enzyme activity of recombinant expressed aromatase. Egonol gentiotrioside was also found to increase the serum estrogen level in ovariectomized rats. These results suggest that these two compounds may promote estrogen biosynthesis through the allosterical regulation of aromatase activity. Egonol gentiobioside and egonol gentiotrioside are, therefore, valuable targets for structural modification and warrant further investigation for their potential as novel pharmaceutical tools for the prevention of estrogen deficiency-induced diseases. (c) 2012 Elsevier B.V. All rights reserved.