Assessment of the effects of naringenin-type flavanones in uterus and vagina
Assessment of the effects of naringenin-type flavanones in uterus and vagina
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DOI：
10.1016/j.jsbmb.2014.10.001
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发表时间：
2015-01-01
影响因子：
4.1
通讯作者：
Zierau, Oliver
中科院分区：
文献类型：
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作者：
Keller, Annekathrin Martina;Doerfelt, Peggy;Zierau, Oliver
具有雌激素特性的植物次生代谢物作为传统激素替代疗法（HRT）的替代品，在缓解绝经后症状方面的潜在利用需要对生殖器官的安全性进行评估。为了评估柚皮素（Nar）、8-烯丙基柚皮素（8PN）和6-（1,1-二甲基）柚皮素（6DMAN）的安全性，我们对大鼠子宫和阴道进行了为期三天的子宫营养试验。此外，我们还研究了这三种物质与肝微粒体孵育产生的代谢物谱。虽然柚皮素未检测到代谢物，但与人和大鼠肝微粒体孵育后，观察到8PN和6DMAN的羟基化产物。母体化合物柚皮素在研究参数中没有引起任何雌激素反应。8PN对子宫湿重、子宫上皮厚度和阴道细胞增生的影响显著增加，对8PN用于人体的安全性提出了质疑。相比之下，在进行的研究中没有观察到6DMAN对生殖器官的雌激素影响，这表明它具有更有希望的安全性，因此有理由进一步研究其缓解绝经后不适的功效。(C) 2014 Elsevier Ltd.版权所有。
The potential utilization of plant secondary metabolites possessing estrogenic properties as alternatives to the classical hormone replacement therapy (HRT) for the relief of postmenopausal complaints asks for an evaluation regarding the safety in reproductive organs. In order to contribute to the estimation of the safety profile of the flavanones naringenin (Nar), 8-prenylnaringenin (8PN) and 6-(1,1-dimethylally) naringenin (6DMAN), we investigated uterus and vagina derived from a three-day uterotrophic assay in rats. Also, we investigated the metabolite profile resulting from the incubation of the three substances with liver microsomes.While no metabolites were detectable for naringenin, hydroxylation products were observed for 8PN and 6DMAN after incubation with human as well as rat liver microsomes.The parent compound naringenin did not evoke any estrogenic responses in the investigated parameters. A significant increase of the uterine wet weight, uterine epithelial thickness and proliferating vaginal cells was observed in response to 8PN, questioning the safety of 8PN if applied in the human situation.In contrast, no estrogenic effects on the reproductive organs were observed for 6DMAN in the conducted study, rendering it the compound with a more promising safety profile, therefore justifying further investigations into its efficacy to alleviate postmenopausal discomforts. (C) 2014 Elsevier Ltd. All rights reserved.