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: 3200688
• 负责人: CARL H ADLERCREUTZ
• 金额: $ 12.26万
• 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/3200688
• 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.

已发现蚕豆含有维生素和间接维生素， 哺乳动物木脂素前体存在于这种豆科植物中。 这些双酚 化合物在许多实验中显示具有抗增殖活性 对于许多类型的癌症的特性，并且还具有许多 其他生物学效应使它们成为癌症的有力候选者 保护剂 本次调查的目的是继续 制定分离、鉴定和定量的方法 测量人体生物体液中的木脂素和木脂素， 特别是在血浆中（用于粪便的方法的开发旨在 将与Mindy Kurzer博士合作， Joanne Slavin博士）。 研究还将侧重于 这些化合物在血浆、粪便和尿液中的结合。 进而 旨在测量已经收集的粪便样本中的这些化合物 不同饮食习惯的女性群体 （长寿者、乳素食者、杂食动物）。 对于这些妇女的饮食 尿液中三种木脂素和两种木脂素的记录和测定结果 已经有了。 此外，还打算继续研究 结构确定的化学合成的生物效应 单独和组合的木脂素和木脂素对培养物中的癌细胞的作用 各种雌激素和抗雌激素。 它还旨在显示， 生物化学和基因技术方法，这些化合物刺激 性激素结合球蛋白（SHBG）在肝细胞中的产生， 它们中的一些抑制芳香酶（雌激素合成酶）。 待使用和待开发的方法主要是基于毛细管 气相色谱-质谱法在选择离子监测模式。 通过离子交换进行纯化和结合物分离 微柱色谱法 氘标记的木脂素（n=3）和 本文合成了四氢呋喃（n=4），并用作内消旋体。 标准品，以校正样品制备过程中的损失。 在一些 在某些情况下，放射免疫分析法将是适当的方法，这是必须的。被 开发 对于用常规细胞培养物进行的生物学实验， 方法学被使用并且对于SHBG和芳香化酶实验常规 生物化学和DNA技术已在实验室建立。 这个实验室提供了大量的氘代和非氘代 木脂素和木脂素的标准提供给许多国家的研究小组 包括美国的许多研究小组和最近（1990年15-16.11，Little Rock，USA）成立的“植物雌激素研究小组”决定， 实验室将，如果资金到位，标准的来源， 这些化合物和这种合成活性。