Role of Phytochemicals in Lifestyle-related Disease Prevention

我们利用我们开发的细胞培养系统和动物模型，研究了几种植物化学物质在生活方式相关疾病预防中的作用。在这些植物化学物质中，我们阐明了大豆异黄酮对生活方式相关疾病的预防有效，对人类健康有益。在调查大豆蛋白和异黄酮对高危苏格兰中年男性血压和胆固醇水平的影响时，我们观察到，摄入大豆营养素的饮食组的收缩压(SBP)和舒张压(DBP)、总胆固醇和非高密度脂蛋白胆固醇水平显著低于基线水平。为了进一步研究预防心血管疾病的饮食因素，我们将世界卫生组织-心脏研究覆盖25个国家的60个研究地点的全球人口分为食用和不食用大豆的人群，并评估了心血管疾病的风险因素。在1801名受试者的24小时异黄酮量测中，食用大豆的受试者的体重指数、SBP和总胆固醇显著低于不食用大豆的受试者。为了阐明异黄酮类的这种作用的机制，我们检验了植物化学物质染料木素可能具有显著的内皮保护作用的假说。金雀异黄素通过下调p22Phox和AT1受体的表达，在转录水平发挥抗氧化剂的作用。我们的数据还表明，PPARγ通路至少部分参与了金雀异黄素抑制p22Phox和AT1受体表达的作用。我们进一步研究了异黄酮苷元(IFA)对卒中易感型自发性高血压大鼠(SHRSP)一氧化氮(NO)和收缩压(SBP)的影响。在给予IFA后，IFA组的SBP与对照组相比显著降低。IFA组的enos基因表达水平也明显高于对照组。

We investigated the effect of several phytochemicals on lifestyle-related disease prevention using a cell culture system and animal models that we developed. Among these phytochemicals, we clarified that soy isoflavones were effective for lifestyle-related disease prevention, and were good for human health.Investigating the effects of soy protein and isoflavones on blood pressure and cholesterol levels among high risk middle-aged Scottish men, we could observed significant reductions from the baselines in systolic blood pressure(SBP) and diastolic blood pressure, total cholesterol and non-high density lipoprotein cholesterol in the group consuming a diet containing soy nutrients. To further investigate dietary factors preventing cardiovascular diseases, we divided world-wide populations examined by the WHO-CARDIAC study covering 60 study sites in 25 countries into the eaters and non-eaters of soybeans and evaluated risk factors for cardiovascular diseases. Among 1801 examinees whose 24h isoflavones were assayed, soy eaters had significantly lower body mass index, SBP and total-cholesterol than non-eaters.To clarify the mechanism of this effect of isoflavones, we tested the hypothesis that genistein, one of the phytochemicals, may exert significant endothelial protection. Genistein acts as an antioxidant at the transcription level by the downregulation of p22phox and AT1 receptor expression. Our data also showed that the PPAR γ pathway was involved, at least in part, in the inhibitory effect of genistein on the expression of p22phox and AT1 receptors. We further studied the effects of isoflavone aglycones(IFA) on the production of nitric oxide(NO) and SBP in stroke-prone spontaneously hypertensive rats(SHRSP). After the administration of IFA, significant decreases in SBP were confirmed in the IFA group compared to the control group. Significantly higher levels of eNOS mRNA were also confirmed in the IFA group than in the control group.