Dietary soy-derived isoflavone phytoestrogens. Could they have a role in coronary heart disease prevention?
Dietary soy-derived isoflavone phytoestrogens. Could they have a role in coronary heart disease prevention?
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DOI：
10.1016/s0006-2952(99)00409-8
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发表时间：
2000-07
影响因子：
5.8
通讯作者：
Matti J. Tikkanen;Herman Adlercreutz
中科院分区：
文献类型：
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作者：
Matti J. Tikkanen;Herman Adlercreutz
含大豆蛋白的食物是植物雌激素的丰富来源，如染料木黄酮和大豆黄酮。人们对这些物质非常感兴趣，因为包括冠心病在内的慢性病发病率较低与含大豆食品的饮食摄入量高有关。大豆植物雌激素与雌激素受体的结合较弱，与雌激素受体-α相比，一些植物雌激素与雌激素受体-β的结合更强。一项荟萃分析表明，植物雌激素降低了最初水平升高的受试者的血浆胆固醇浓度，但对胆固醇浓度正常的受试者几乎没有影响。据报道，这些物质也可能对动脉内皮功能具有有益作用。除了这些潜在的抗动脉粥样硬化作用外，许多实验室正在研究其他可能的机制，包括这些物质的抗氧化和抗增殖特性。我们已经证明，饮食中补充大豆衍生的异黄酮降低了低密度脂蛋白（LDL）的体外氧化敏感性。为了进一步探索这一现象，我们将染料木黄酮和大豆苷元纳入低密度脂蛋白分子在体外的人工转移系统的援助。然而，有必要将雌激素分子转化为脂溶性衍生物，脂肪酸酯（类似于酯化的内源性雌激素，已知其在体内发生），以实现显著的掺入。含有酯化胆甾酮的LDL在体外比天然LDL更不易氧化。我们还采用U937细胞培养物研究含孕酮的LDL对细胞增殖的影响。这些LDL中的一些在培养的U937细胞中表现出抗增殖作用。总之，亲脂性植物雌激素衍生物可以掺入LDL中，增加其体外抗氧化性和抗增殖功效，理论上，这两者都是抗动脉粥样硬化作用。还需要进一步研究，以评估在何种程度上可以在体内产生类似的效果，以及这些物质是否在绝经后妇女的激素替代和冠心病预防中发挥作用。
Soy protein-containing foods are a rich source of isoflavone phytoestrogens, such as genistein and daidzein. There is great interest in these substances, as lower rates of chronic diseases, including coronary heart disease, have been associated with high dietary intake of soy-containing foods. Soy phytoestrogens bind weakly to estrogen receptors, and some bind more strongly to estrogen receptor-β compared with estrogen receptor-α. A meta-analysis has indicated that isoflavone phytoestrogens lowered plasma cholesterol concentrations in subjects with initially elevated levels, but had little effect in subjects with normal cholesterol concentrations. These substances reportedly may also have beneficial effects on arterial endothelial function. In addition to these potentially antiatherogenic effects, many laboratories are investigating other possible mechanisms, including antioxidative and antiproliferative properties of these substances. We have shown that dietary supplementation with soy-derived isoflavones reduced the in vitro oxidation susceptibility of low-density lipoprotein (LDL). To further explore this phenomenon, we incorporated genistein and daidzein into LDL molecules in vitro with the aid of an artificial transfer system. However, it was necessary to convert the isoflavone molecules to fat-soluble derivatives, fatty acid esters (analogous to esterified endogenous estrogens, which are known to occur in vivo), to achieve significant incorporation. The LDLs containing esterified isoflavones were shown to be less susceptible to oxidation in vitro than native LDL. We also employed U937 cell cultures for investigating the effects of isoflavone-containing LDLs on cell proliferation. Some of these LDLs exhibited antiproliferative effects in cultured U937 cells. In summary, lipophilic phytoestrogen derivatives could be incorporated into LDLs, increasing their oxidation resistance and antiproliferative efficacy ex vivo, both of which are, in theory, antiatherogenic effects. Further studies are needed to assess to what extent analogous effects could be produced in vivo and whether such substances have a role in hormone replacement and coronary heart disease prevention in postmenopausal women.