Taubert Dirk, Berkels Reinhard, Klaus Wolfgang, Roesen Renate
Department of Pharmacology, University of Cologne, Cologne, Germany.
J Cardiovasc Pharmacol. 2002 Nov;40(5):701-13. doi: 10.1097/00005344-200211000-00008.
The high intake of polyphenols is thought to contribute to the beneficial cardiovascular effects of plant-centered diets. A putative mechanism underlying the cardioprotective activity is thought to be a plant phenol-induced increase of nitric oxide formation by the constitutive endothelial nitric oxide synthase. Twenty-eight phenols of different classes commonly occurring in plant foods were examined for their capability of enhancing the endothelial nitric oxide release of isolated porcine coronary arteries by direct real-time measurement of the luminal surface nitric oxide concentration with an amperometric microsensor. Additionally, the relaxing activity of the phenols was measured on porcine coronary rings. Quercetin, myricetin, leucocyanidol, and oligomeric proanthocyanidins induced the highest increases in nitric oxide release (delta[NO] > 8.5 nM ); caffeic acid, fisetin, hyperosid, and isoquercitrin were moderately active (5 nM < delta[NO] < 8.5 nM ); the other phenolic compounds caused only marginal increases of the nitric oxide levels (delta[NO] < 5 nM). The nitric oxide-stimulating activity of the phenols was uniformly positively correlated with their vasorelaxing activity. However, endothelium-dependent vasorelaxations were limited to phenols inducing nitric oxide elevations > 5 nM (= Km value of the soluble guanylate cyclase). Analysis of structure-activity relations revealed that a high nitric oxide activity was confined to a flavan-moiety with free hydroxyl-residues at C3, C3', C4', C5, and C7 and a hydroxyl-, oxo-, or phenolic substituent at C4, whereas the caffeic acid scaffolding emerged as the minimally essential motif for the nitric oxide-dependent vasorelaxation.
多酚的高摄入量被认为有助于以植物为中心的饮食对心血管产生有益影响。心脏保护活性的一种潜在机制被认为是植物酚通过组成型内皮型一氧化氮合酶诱导一氧化氮生成增加。通过使用安培微传感器直接实时测量管腔表面一氧化氮浓度，研究了植物性食物中常见的28种不同类别的酚类物质增强离体猪冠状动脉内皮一氧化氮释放的能力。此外，还测量了这些酚类物质对猪冠状动脉环的舒张活性。槲皮素、杨梅素、无色花青素和低聚原花青素诱导的一氧化氮释放增加最多（δ[NO]>8.5 nM）；咖啡酸、漆黄素、金丝桃苷和异槲皮苷活性中等（5 nM<δ[NO]<8.5 nM）；其他酚类化合物仅使一氧化氮水平略有增加（δ[NO]<5 nM）。酚类物质的一氧化氮刺激活性与其血管舒张活性一致呈正相关。然而，内皮依赖性血管舒张仅限于诱导一氧化氮升高>5 nM（=可溶性鸟苷酸环化酶的Km值）的酚类物质。结构-活性关系分析表明，高一氧化氮活性仅限于在C3、C3'、C4'、C5和C7处具有游离羟基残基且在C4处具有羟基、氧代或酚取代基的黄烷部分，而咖啡酸支架是一氧化氮依赖性血管舒张的最低必需基序。
