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，雌马酚，大豆异黄酮大豆苷元的主要代谢物，具有重要的心脏保护作用。然而，雌马酚是由大豆苷元通过细菌下消化道酶的活性产生的，其在体内的生物活性尚不清楚。在拟议的研究中，马雌酚的动脉粥样硬化抑制活性将直接使用无菌和人类菌群相关apoE null（动脉粥样硬化易感）小鼠进行研究。此外，我们实验室的证据表明，浓缩的7S部分具有显著的动脉粥样硬化抑制作用，7S是大豆中约30%的蛋白质储存蛋白。可能存在的添加剂/相互作用的营养素，可以提高心血管的好处大豆补充剂对人类的可能性很少受到关注。本文提出的研究将进一步探讨异黄酮和7S组分对动脉粥样硬化斑块发展的个体和附加/相互作用影响。还将评估与斑块易损性相关的形态学和形态学特征。最后，由于异黄酮和7S球蛋白介导抗动脉粥样硬化作用的途径是不确定的，似乎不依赖于对血浆脂蛋白的影响，1)这些干预措施对动脉粥样硬化中涉及的氧化和炎症途径的影响将被研究，2)使用DNA微阵列和qRT-PCR技术，候选基因将被确定，以进一步研究通过大豆及其成分介导的动脉粥样硬化保护作用的途径。由于只有大约1/3的美国人产生雌马酚，因此研究结果将提供证据，表明以下探索是否有利：1)益生菌方法诱导非生产者产生雌马酚；2)在膳食补充剂中使用浓缩雌马酚或某些大豆蛋白组分；3)在膳食补充剂中联合使用多肽和异黄酮。

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.