Botanical Center for Age-Related Diseases

描述（由申请人提供）：几种含有异黄酮的植物产品作为雌激素替代疗法的替代品正在上市，以预防绝经后妇女骨质疏松症。雌激素抑制骨吸收，并可能增加钙的吸收。异黄酮对骨骼健康的功效有不同的结果，这可能取决于异黄酮的剂量和相互作用以及个体产生雌马酚的能力。具体目的1是确定染料木素的剂量效应以及与其他大豆异黄酮的相互作用对绝经后雌马酚和非雌马酚产生者的钙吸收和骨吸收的影响。我们将使用41Ca（一种长寿命同位素）来标记骨架，并使用加速器质谱（AMS）来监测饮食的扰动。这种研究骨吸收的创新方法是一种直接测量骨吸收的方法，与骨转换的生化标志物和传统的钙动力学相比，与研究骨密度的变化相比，这种方法是快速的，并且不像骨组织形态测量法那样具有侵入性。我们能够通过测量尿液中41Ca排泄的变化，系统地确定不同类型和剂量的含异黄酮植物产品对同一绝经后妇女抑制骨吸收的效果。初步证据表明，作为雌激素替代品销售的葛根可以减少骨质流失，这可能与一种不寻常的异黄酮葛根素有关。特异性目的2：在去卵巢大鼠模型中，测量染料木素、葛根和马雌酚对骨和骨质量的剂量效应。具体目的3是研究大豆和葛根中异黄酮的代谢。我们已经具备了制备C-14和C-13标记植物组织培养物的能力。通过植入微透析探针给大鼠灌胃纯化或粗馏分，我们可以跟踪生物活性化合物在全身的代谢命运。微小的数量可以用AMS和microNMR进行追踪。

DESCRIPTION (provided by applicant): Several types of botanical products containing isoflavones are being marketed as an alternative to estrogen replacement therapy to prevent osteoporosis in postmenopausal women. Estrogen suppresses bone resorption and may increase calcium absorption. Efficacy of isoflavones on bone health has mixed results, which may depend on the dose and interaction of isoflavones and the ability of individuals to produce equol. Specific Aim 1 is to determine the dose response of effect of genistein and the interaction with other soy isoflavones on calcium absorption and bone resorption in postmenopausal women who are equol vs. nonequolproducers. We will use 41Ca, a long-lived isotope, to label the skeleton and an Accelerator Mass Spectrometry (AMS) to monitor perturbations by diet. This innovative approach to study bone resorption is a direct measure of bone resorption in contrast to biochemical markers of bone turnover and traditional calcium kinetics, rapid compared to studying changes in bone density, and not invasive as is bone histomorphometry. We are able to systematically determine the effect of various types and dosages of isoflavone-containing botanical products sequentially in the same postmenopausal women for their effectiveness in suppressing bone resorption by measuring changes in 41Ca excretion in the urine. Preliminary evidence indicates that kudzu root, marketed as an estrogen replacement, reduces bone loss, which may relate to an unusual isoflavone, puerarin. Specific Aim 2 is to measure the dose response effect of genistein, kudzu, and equol on bone and bone quality in an ovariectomized rat model. Specific Aim 3 is to study metabolism of isoflavones in soybeans and kudzu. We have developed the ability to prepare C-14 and C-13 labeled plant tissue culture. By gavaging purified or crude fractions to rats with implanted microdialysis probes, we can follow the metabolic fate of bioactive compounds throughout the body. Minute quantities can be traced with AMS and microNMR.