METABOLISM OF SOYBEAN ISOFLAVONOIDS AND LIGNANS IN MAN

大豆异黄酮和木脂素在人体中的代谢

• 批准号: 3200687
• 负责人: CARL H ADLERCREUTZ
• 金额: $ 9.69万
• 依托单位: UNIVERSITY OF HELSINKI
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3200687
• 关键词: aromatase; body fluids; chemical conjugate; deuterium; diet; drug metabolism; estrogen inhibitor; estrogens; feces analysis; flavonoids; gas chromatography mass spectrometry; globulins; human subject; human tissue; ion exchange chromatography; lignans; neoplastic cell; nutrition related tag; plasma; radioimmunoassay; radiotracer; saliva; soybeans; tissue /cell culture; urinalysis; vegetarian diet

Soybeans have been found to contain isoflavonoids and indirect that also mammalian lignan precursors occur in this legume. These diphenolic compounds have in numerous experiments been shown to have antiproliferative properties with regard to many types of cancer and have in addition many other biological effects making them strong candidates for a role as cancer protective agents. The aim of the present investigation is to continue to develop methodology for the isolation, identification and quantitative measurements of lignans and isoflavonoids in human biological fluids, particularly in plasma (the development of a method for feces is intended to be carried out with a subcontract in collaboration with Dr Mindy Kurzer and Dr Joanne Slavin). Studies will also be focused on the type of conjugation of these compounds in plasma, feces and urine. Furthermore it is intended to measure these compounds in already collected feces samples of groups of women consuming different types of habitual diets (macrobiotics, lactovegetarians, omnivores). For these women dietary records and assay results of three isoflavonoids and two lignans in urine are already available. Furthermore it is intended to continue studies on the biological effects of structurally defined chemically synthesized lignans and isoflavonoids on cancer cells in culture, alone and combined with various estrogens and antiestrogens. It is also intended to show by biochemical and gene technological methods that these compounds stimulate sex hormone binding globulin (SHBG) production in hepatic cells and that some of them.inhibit the aromatase (estrogen synthetase) enzyme. The methods to be used and to be developed are mainly based on capillary gas chromatography-mass spectrometry in the selected ion monitoring mode. Purification and conjugate separation is carried out by ion exchange chromatography in microcolumns. Deuterium-labelled lignans (n=3) and isoflavonoids (n=4) have been synthesized and are used as internal standards to correct for losses during preparation of the samples. In some instances radioimmunoassay will be the appropriate method,which has to. be developed. For the biological experiments with cell cultures conventional methodology is used and for the SHBG and aromatase experiments routine biochemical and DNA techniques have been established in the laboratory. This laboratory has provided numerous deuterated and nondeuterated standards of lignans and isoflavonoids to research groups in many countries including many research groups in USA and a newly (15-16.11 1990, Little Rock, USA) formed "Phytoestrogen Research Group" decided that our laboratory will be, if funds are available, the source of standards for these compounds and this synthetic activity.

大豆被发现含有异黄酮类化合物，间接也 哺乳动物的木脂素前体存在于这种豆科植物中。这些双酚类 许多实验表明化合物具有抗增殖性。 与许多类型的癌症有关的特性，此外还有许多 其他生物效应使它们成为癌症的有力候选者 防护剂。目前调查的目的是继续 建立分离、鉴定和定量的方法学 人体体液中木脂素和异黄酮类化合物的测定， 特别是在血浆中(意在开发一种粪便检测方法 将通过与Mindy Kurzer博士合作的分包合同进行 和乔安妮·斯莱文博士)。研究还将集中在 这些化合物在血浆、粪便和尿液中的结合。此外，它还 旨在测量已经收集的粪便样本中的这些化合物 消费不同类型的习惯性饮食的妇女群体 (长生生物、乳素、杂食动物)。对于这些女性来说，饮食 三种异黄酮类和两种木脂素在尿液中的记录和检测结果 已经可以使用了。此外，它还打算继续研究 结构明确的化学合成化合物的生物学效应 单独和联合培养对癌细胞的木脂素和异黄酮类化合物 含有多种雌激素和抗雌激素。它还打算通过以下方式展示 这些化合物刺激的生化和基因技术方法 肝细胞产生性激素结合球蛋白 其中一些。抑制芳香酶(雌激素合成酶)酶。 要使用和要开发的方法主要是基于毛细管的 所选择的离子监测模式下的气相色谱-质谱法。 提纯和共轭分离是通过离子交换进行的 微柱层析。氚标记木脂素(n=3)和 合成了异黄酮类化合物(n=4)，并将其作为内源化合物。 标准，以纠正样品制备过程中的损失。在一些 实例放射免疫分析将是合适的方法，这是必须的。BE 发展起来的。用于常规细胞培养的生物学实验 方法学用于SHBG和芳香酶实验例程 生化和DNA技术已经在实验室建立起来。 这个实验室已经提供了大量的重氢和非重氢 许多国家研究小组的木脂素和异黄酮类标准 包括美国的许多研究小组和一个新的(15-16.11 1990，Little 美国罗克)成立了“植物雌激素研究小组”，决定我们的 如果资金可用，实验室将是标准的来源 这些化合物和这种合成活性。