Botanical Center for Age-Related Diseases

描述(申请人提供)：几种含有异黄酮类的植物产品正作为雌激素替代疗法上市，以预防绝经后妇女的骨质疏松症。雌激素抑制骨吸收，并可能增加钙的吸收。异黄酮类对骨骼健康的疗效有好有坏，这可能取决于异黄酮类药物的剂量和相互作用，以及个体产生马醇的能力。具体目的1是确定染料木素对绝经后妇女钙吸收和骨吸收的剂量效应，以及与其他大豆异黄酮的相互作用。我们将使用长寿命的同位素41Ca来标记骨骼，并使用加速器质谱仪(AMS)来监测饮食的扰动。这种研究骨吸收的创新方法是骨吸收的直接测量，与骨转换和传统钙动力学的生化标记物相比，与研究骨密度的变化相比，它更快，而且不像骨组织形态计量学那样具有侵入性。我们能够通过测量尿中41Ca排泄的变化，系统地测定不同类型和剂量的含异黄酮类植物产品在同一绝经后妇女体内抑制骨吸收的效果。初步证据表明，葛根，作为一种雌激素替代品，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。具体目标2是在去卵巢的大鼠模型上测量金雀异黄素、葛根和马兜铃对骨和骨质量的剂量反应效应。具体目标3是研究大豆和葛根中异黄酮的代谢。我们已经发展了制备C-14和C-13标记植物组织培养的能力。通过将纯化的或粗制的部分与植入的微透析探针一起灌胃给大鼠，我们可以跟踪生物活性化合物在全身的代谢命运。微量可用AMS和显微核磁共振进行追踪。

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.