DIETARY SOY SUPPLEMENTS: CARDIOPROTECTIVE MECHANISMS

描述（由申请人提供）：尽管经过数十年的研究，大豆的心脏保护成分及其发挥作用的方式仍不清楚。越来越多的证据间接表明，大豆黄酮的主要代谢产物雌马酚具有显著的心脏保护活性。然而，牛尿酚是通过下胃肠道中细菌酶的活性由大豆苷元产生的，并且对其体内生物活性知之甚少。在拟定的研究中，将直接使用无菌和人菌群相关apoE null（动脉粥样硬化可耐受）小鼠研究雌马酚的动脉粥样硬化抑制活性。此外，来自我们实验室的证据表明浓缩7S组分具有显著的动脉粥样硬化抑制作用，7S组分是一种储存蛋白，占大豆蛋白质的约30%。营养素的添加/相互作用可能会增强大豆补充剂对人类心血管的益处，但这种可能性很少受到关注。这里提出的研究将进一步解决的个人和添加剂/交互作用的影响，对动脉粥样硬化斑块的发展，马诺酮和7S馏分。还将评估与斑块脆弱性相关的形态学和形态测量特征。最后，由于β-胆甾酮和7S球蛋白介导抗动脉粥样硬化作用的途径不确定，似乎不依赖于对血浆脂蛋白的作用，1）将研究这些干预对动脉粥样硬化中涉及的氧化和炎症途径的作用，2）使用DNA微阵列和qRT-PCR技术，将鉴定候选基因，以进一步研究大豆及其成分介导的动脉粥样硬化保护作用的途径。由于只有约1/3的美国人产生雌马酚，因此结果将提供证据以表明探索1）益生菌方法以诱导非生产者人类产生雌马酚，2）在膳食补充剂中使用浓缩的雌马酚或某些大豆蛋白级分和3）在膳食补充剂中组合使用肽和雌马酮两者是否可能是有利的。

DESCRIPTION (provided by applicant): Despite decades of study, the cardioprotective component(s) of soy and the means by which they exert their effects remains unclear. An accumulating body of evidence indirectly implicates equol, the major metabolite of the soy isoflavone daidzein, as having substantial cardioprotective activity. However, equol is produced from daidzein by the activity of bacterial enzymes in the lower Gl tract, and little is known about its biological activity in vivo. In the proposed studies, the athero-inhibitory activity of equol will be addressed directly using germ-free and human flora-associated apoE null (atherosclerosis-susceptable) mice. In addition, evidence from our lab demonstrates a marked athero-inhibitory effect of concentrated 7S fraction, a storage protein that accounts for about 30% of the protein in soy beans. The possibility that there are additive/interactive effects of nutrients that could enhance the cardiovascular benefits of soy supplements in human beings has received little attention. The studies proposed here will address further the individual and additive/interactive influence of isoflavones and 7S fraction on the development of atherosclerotic plaques. Assessments will also be made of morphologic and morphometric characteristics associated with plaque vulnerability. Finally, since the pathways through which isoflavones and 7S globulin mediate antiatherosclerotic effects are uncertain and do not appear to depend on effects on plasma lipoproteins, 1) the effects of these interventions on oxidative and inflammatory pathways implicated in atherosclerosis will be studied and 2) using DNA micro-array and qRT-PCR techniques, candidate genes will be identified for further investigation into pathways through which atheroprotective effects of soy and its components are mediated. Since only about 1/3 of American human beings produce equol, the results will provide evidence to indicate whether it may be advantageous to explore 1) probiotic approaches to inducing equol production in non-producer human beings, 2) the use of concentrated equol or certain soy protein fractions in dietary supplements and 3) the combined use of both peptides and isoflavones in dietary supplements.