PROJECT 1 - ISOFLAVONES AND BONE HEALTH

项目 1 - 异黄酮和骨骼健康

基本信息

批准号：
7558658
负责人：
Connie Marie Weaver
金额：
$ 12.82万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7558658
关键词：
Address Biochemical Markers Bone Density Bone Resorption Botanicals C14 isotope Calcium Cardiovascular Diseases Clinical Trials Data Monitoring Committees Colorectal Cancer Data Diet Dose Drug Kinetics Effectiveness Enrollment Estrogen Replacement Therapy Estrogen Replacements Estrogen Therapy Estrogens Excretory function Fracture Funding Genistein Glucosides Glycine max Hormone replacement therapy Human Implant Individual Intervention Invasive Isoflavones Isotopes Kinetics Kudzu Label Life Marketing Mass Spectrum Analysis Measures Menopause Metabolic Microdialysis Modeling Monitor Object Attachment Osteoporosis Other Finding Outcome Measure Phytoestrogens Plant Roots Plants Postmenopause Premenopause Prevention Progesterone Publishing Randomized Randomized Controlled Trials Rattus Recommendation Reporting Research Personnel Risk Serum Skeleton Societies Soybeans Stroke Tissues Tracer Upper arm Urine Woman Women&apos s Health absorption accelerator mass spectrometry analog bisphosphonate bone bone health bone loss bone quality bone turnover calcium metabolism daidzein day density dietary supplements dosage equol feeding innovation insight ipriflavone malignant breast neoplasm metabolic abnormality assessment novel strategies prevent programs protective effect puerarin response risedronate sodium size soy soy protein isolate tissue culture treatment effect

项目摘要

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 ofgenistein 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 4lCa 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 ofgenistein, 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 labled 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.

几种类型的含有异黄酮的植物产品正在销售，以替代雌激素替代疗法，以防止绝经后妇女的骨质疏松症。雌激素抑制骨吸收，并可能增加钙吸收。异黄酮对骨骼健康的疗效的结果混合的结果可能取决于异黄酮的剂量和相互作用以及个体产生雌激素的能力。具体目的1是确定基因蛋白酶作用的剂量反应以及与其他大豆异黄酮对钙后妇女的钙吸收和骨吸收的相互作用，这些妇女与非验证剂相比。我们将使用41CA（一种长寿命的同位素）来标记骨骼和加速器质谱法（AMS）来通过饮食来监测扰动。与研究骨密度变化相比，这种研究骨吸收的创新方法是骨吸收的直接衡量，与骨密度变化相比，骨骼更新和传统钙动力学的生化标志相比，迅速，而不是侵入性的骨骼组态学法。我们能够系统地确定绝经后女性在同一绝经后妇女中依次确定含异黄酮的植物产物的效果，因为她们通过测量尿液中4LCA排泄的变化来抑制骨吸收的有效性。初步证据表明，作为雌激素替代品销售的库祖根可以减少与异常异黄酮Puerarin有关的骨质流失。具体目的2是测量卵巢切除大鼠模型中产蛋白酶，kudzu和quol对骨和骨质质量的剂量反应效应。具体目的3是研究大豆和库祖的异黄酮的代谢，我们发展了制备C-14和C-13易于植物组织培养的能力。通过用植入的微透析探针将纯化或粗馏分浸入大鼠，我们可以遵循整个体内生物活性化合物的代谢命运。可以用AMS和MicrONMR追踪分钟数量。