DIETARY SOY SUPPLEMENTS: CARDIOPROTECTIVE MECHANISMS

描述(申请人提供)：尽管经过几十年的研究，大豆的心脏保护成分(S)及其发挥作用的方式仍然不清楚。越来越多的证据间接表明，大豆异黄酮型大豆苷元的主要代谢物马醇具有显著的心脏保护活性。然而，马酚是由大豆苷元通过低Gl区细菌酶的活性而产生的，对其在体内的生物活性知之甚少。在拟议的研究中，将使用无菌和人类菌群相关的apoE空(动脉粥样硬化易感性)小鼠直接研究Equol的动脉粥样硬化抑制活性。此外，我们实验室的证据表明，浓缩的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质，约占大豆蛋白质的30%。营养物质的相加/交互作用可能会增强大豆补充剂对人类心血管的益处，这一可能性几乎没有受到关注。本文建议的研究将进一步探讨异黄酮组分和7S组分对动脉粥样硬化斑块发展的单独和相加/交互作用的影响。还将对与斑块脆弱性相关的形态和形态特征进行评估。最后，由于异黄酮类和7S球蛋白介导抗动脉粥样硬化作用的途径尚不确定，而且似乎不依赖于对血浆脂蛋白的影响，1)这些干预措施对与动脉粥样硬化有关的氧化和炎症途径的影响将被研究，2)利用DNA微阵列和qRT-PCR技术，候选基因将被确定，以便进一步研究大豆及其成分介导动脉粥样硬化保护作用的途径。由于只有约三分之一的美国人产生马醇，研究结果将提供证据表明，探索1)益生菌方法在非生产型人类中诱导马醇产生可能是有利的，2)在膳食补充剂中使用浓缩马醇或某些大豆蛋白组分，3)在膳食补充剂中同时使用多肽和异黄酮。

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.