Roth A, Schaffner W, Hertel C
F. Hoffmann-LaRoche Ltd, Pharma Research Preclinical, Basel, Switzerland.
J Neurosci Res. 1999 Aug 1;57(3):399-404.
In clinical studies, it has been shown that estrogen replacement therapy in menopause is strongly correlated with a reduced risk of the development of Alzheimer's disease (AD). In in vitro experiments, it was demonstrated that estradiol protects cells against the toxic effects of beta-amyloid, the major component of plaques in brains of AD patients. Therefore, estrogens have become interesting candidates for a possible treatment of neurodegeneration. In plants, a class of compounds has been identified that bind to human estrogen receptor, so-called phytoestrogens, which are part of our daily diet. Here, we compared the effects of alpha- and beta-estradiol with plant-derived kaempferol on beta-amyloid peptide-induced toxicity in PC12 neuroblastoma and T47D human breast cancer cells. The present results demonstrate a protective effect of kaempferol comparable to that observed with estradiol. The effects of the weak estrogen receptor agonists alpha-estradiol and kaempferol were found to be similar to the effects of the strong estrogen receptor agonist beta-estradiol, suggesting a mode of action independent from the nuclear estrogen receptor.
在临床研究中，已表明更年期雌激素替代疗法与降低患阿尔茨海默病（AD）的风险密切相关。在体外实验中，已证明雌二醇可保护细胞免受β-淀粉样蛋白的毒性作用，β-淀粉样蛋白是AD患者大脑中斑块的主要成分。因此，雌激素已成为可能治疗神经退行性变的有趣候选物。在植物中，已鉴定出一类与人类雌激素受体结合的化合物，即所谓的植物雌激素，它们是我们日常饮食的一部分。在此，我们比较了α-雌二醇和β-雌二醇与植物来源的山奈酚对PC12神经母细胞瘤和T47D人乳腺癌细胞中β-淀粉样肽诱导毒性的影响。目前的结果表明，山奈酚的保护作用与雌二醇观察到的作用相当。发现弱雌激素受体激动剂α-雌二醇和山奈酚的作用与强雌激素受体激动剂β-雌二醇的作用相似，表明其作用方式独立于核雌激素受体。
