METABOLISM OF SOYBEAN ISOFLAVONOIDS AND LIGNANS

大豆异黄酮和木脂素的代谢

• 批准号: 2097206
• 负责人: CARL H ADLERCREUTZ
• 金额: $ 10.36万
• 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/2097206
• 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.

已经发现大豆包含异黄素和间接的大豆 哺乳动物的木质木质前体发生在此豆类中。 这些二苯酚 在许多实验中，具有抗增生性的化合物 关于多种类型的癌症的特性，还有许多 其他生物学作用使他们成为癌症角色的强大候选人 保护剂。 本调查的目的是继续 开发隔离，识别和定量的方法 人类生物体流体中木质脂蛋白和异黄素的测量， 特别是在血浆中（粪便方法的开发是旨在的 与分包合同与Mindy Kurzer博士合作进行 和Joanne Slavin博士）。 研究也将集中于 这些化合物在血浆，粪便和尿液中的结合。 此外 旨在测量已经收集的粪便样品中的这些化合物 一群食用不同类型习惯饮食的妇女 （大生物学，乳酸植物，杂食动物）。 对于这些女性饮食 尿液中三种异黄素和两个木质的记录和测定结果 已经可用。 此外，旨在继续研究 结构定义的化学合成的生物学作用 单独和合并 具有各种雌激素和抗雌激素。 它也旨在显示 这些化合物刺激的生化和基因技术方法 性激素结合球蛋白（SHBG）在肝细胞中的产生， 其中一些抑制了芳香酶（雌激素合成酶）酶。 要使用和开发的方法主要基于毛细管 在选定的离子监测模式下，气相色谱 - 质量光谱法。 通过离子交换进行纯化和共轭分离 微柱中的色谱。 氘标记的木质木质（n = 3）和 异黄素（n = 4）已合成并用作内部 在制备样品期间纠正损失的标准。 在某些人中 实例放射免疫分析将是必须的适当方法。是 发达。 用于细胞培养的生物学实验常规 使用方法，用于SHBG和芳香酶实验常规 在实验室中已经建立了生化和DNA技术。 该实验室提供了众多的申请和非侵犯 许多国家的研究小组的木叶兰人和异黄素标准 包括美国的许多研究小组和一个新的研究小组（1990年15-16.11，很少 美国洛克）形成的“植物雌激素研究小组”决定我们 如果有资金，实验室将是标准的来源 这些化合物和这种合成活性。