Tissue specificity of 8-prenylnaringenin:: Protection from ovariectomy induced bone loss with minimal trophic effects on the uterus
Tissue specificity of 8-prenylnaringenin:: Protection from ovariectomy induced bone loss with minimal trophic effects on the uterus
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DOI：
10.1016/j.jsbmb.2005.05.009
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发表时间：
2005-11-01
影响因子：
4.1
通讯作者：
Schleuning, WD
中科院分区：
文献类型：
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作者：
Hümpel, M;Isaksson, P;Schleuning, WD
植物次生代谢产物具有雌激素活性（植物雌激素）已被研究在过去作为一个潜在的替代经典的绝经期妇女的激素替代疗法（HRT）。尽管进行了大量的临床研究，但对基于大豆或红三叶草的药物制剂的功效还没有得出最终的结论。我们研究了新的和最有效的植物雌激素8-prenylnaringenin（8-PN）在成年卵巢切除大鼠，建立动物模型，以模拟激素依赖性骨质疏松症的绝经期妇女。我们的研究结果表明，8-PN可以完全防止卵巢切除术引起的骨丢失，同时对子宫和子宫内膜表现出最小的（剂量依赖性）营养作用。据估计，在17 β-雌二醇和8-PN的等效骨保护剂量下，植物雌激素对子宫和子宫内膜的刺激作用低10倍。在转基因报告小鼠模型（ERE-Luc小鼠）中证实了8-PN的骨组织特异性效应。在这里，我们还发现了前列腺明显的雌激素活性。目前的研究结果增加了重要方面的药理学特征的8-PN和定位这种化合物作为一个有趣的替代新的候选人治疗绝经后和绝经后症状。(c)2005爱思唯尔有限公司保留所有权利。
Plant secondary metabolites with estrogenic activity (phyto-estrogens) have been studied in the past as a potential alternative to classical hormone-replacement therapy (HRT) in menopausal women. No final verdict on the efficacy of soy or red clover based pharmaceutical preparations has been reached despite numerous clinical studies. We have studied the novel and most potent phyto-estrogen 8-prenylnaringenin (8-PN) in adult ovariectomized rats, an established animal model to mimic hormone dependent osteoporosis in menopausal women. Our results demonstrate that 8-PN can completely protect from ovariectomy induced bone-loss while exhibiting minimal, (dose independent) trophic effects on uterus and endometrium. It is estimated that at equivalent bone protective doses of 17 beta-estradiol and 8-PN, the phyto-estrogen has a 10-fold lower stimulatory effect on uterus and endometrium. The bone tissue specific effect of 8-PN was confirmed in a transgenic reporter mouse model (ERE-Luc mice). Here we also found pronounced estrogenic activity in prostate. Present results add important aspects to the pharmacological profile of 8-PN and position this compound as an interesting alternative new candidate for treatment of peri- and postmenopausal symptoms. (c) 2005 Elsevier Ltd. All rights reserved.