Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, UK.
J Agric Food Chem. 2010 Apr 14;58(7):4008-13. doi: 10.1021/jf9031876.
Flavonoid-rich diets are associated with a lower mortality from cardiovascular disease. This has been linked to improvements in endothelial function. However, the specific flavonoids, or biologically active metabolites, conferring these beneficial effects have yet to be fully defined. In this experimental study of the effect of flavonoids on endothelial function cultured endothelial cells have been used as a bioassay with endothelin-1 (ET-1) synthesis being measured an index of the response. Evaluation of the relative effects of extracts of cranberry juice compared to apple, cocoa, red wine, and green tea showed inhibition of ET-1 synthesis was dependent primarily on their oligomeric procyanidin content. Procyanidin-rich extracts of cranberry juice triggered morphological changes in endothelial cells with reorganization of the actin cytoskeleton and increased immunostaining for phosphotyrosine residues. These actions were independent of antioxidant activity. Comparison of the effects of apple procyanidin monomers through heptamer showed a clear structure-activity relationship. Although monomer, dimer, and trimer had little effect on ET-1 synthesis, procyanidin tetramer, pentamer, hexamer, and heptamer produced concentration-dependent decreases with IC(50) values of 5.4, 1.6, 0.9, and 0.7 microM, respectively. Levels of ET-1 mRNA showed a similar pattern of decreases, which were inversely correlated with increased expression of Kruppel-like factor 2 (KLF2), a key endothelial transcription factor with a broad range of antiatherosclerotic actions including suppression of ET-1 synthesis. Future investigations of procyanidin-rich products should assess the role KLF2 induction plays in the beneficial vascular effects of high flavonoid consumption.
富含类黄酮的饮食与心血管疾病死亡率降低有关。这与内皮功能的改善有关。然而，赋予这些有益作用的特定类黄酮或生物活性代谢物尚未完全确定。在这项关于类黄酮对内皮功能影响的实验研究中，使用培养的内皮细胞作为生物测定法，测量内皮素-1 (ET-1) 的合成作为反应的指标。评估蔓越莓汁提取物与苹果、可可、红酒和绿茶提取物的相对作用，结果表明 ET-1 合成的抑制主要取决于它们的低聚原花青素含量。蔓越莓汁中原花青素丰富的提取物会引发内皮细胞的形态变化，使肌动蛋白细胞骨架重新排列，并增加磷酸酪氨酸残基的免疫染色。这些作用与抗氧化活性无关。通过七聚体比较苹果原花青素单体的作用，显示出明显的结构-活性关系。尽管单体、二聚体和三聚体对 ET-1 合成几乎没有影响，但原花青素四聚体、五聚体、六聚体和七聚体产生浓度依赖性的降低，IC50 值分别为 5.4、1.6、0.9 和 0.7 μM。ET-1 mRNA 的水平也表现出类似的降低模式，与 Kruppel 样因子 2 (KLF2) 的表达增加呈负相关，KLF2 是一种关键的内皮转录因子，具有广泛的抗动脉粥样硬化作用，包括抑制 ET-1 合成。对富含原花青素的产品的未来研究应评估 KLF2 诱导在高类黄酮摄入的有益血管作用中所起的作用。
