Favot Laure, Martin Sophie, Keravis Thérèse, Andriantsitohaina Ramaroson, Lugnier Claire
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Université Louis Pasteur de Strasbourg, 74 Route du Rhin, B.P. 24, 67401 Illkirch, France.
Cardiovasc Res. 2003 Aug 1;59(2):479-87. doi: 10.1016/s0008-6363(03)00433-4.
Epidemiologic studies have shown that a diet rich in fruits and vegetables has a beneficial preventive effect for cancer and cardiovascular diseases. The mechanisms of these beneficial effects are not known although there is evidence that polyphenolic compounds in food may be of some benefit. The purpose of this study was to define the effect of delphinidin, a vasoactive polyphenol belonging to the class of anthocyanin, on endothelial cell proliferation and migration as well as on in vivo angiogenesis.
Vascular endothelial growth factor-stimulated human umbilical endothelial cell migration and proliferation are potently inhibited by delphinidin. Flow cytometric analysis demonstrates that delphinidin inhibition of proliferation is correlated with the blockade of cell cycle in G(0)/G(1) phase. Western blot analysis shows that delphinidin reverses the vascular endothelial growth factor-induced decrease in expression of cyclin-dependent kinase inhibitor p27(kip1) and the vascular endothelial growth factor-induced increase of cyclin D1 and cyclin A, both being necessary to achieve the G(1)-to-S transition. Furthermore, delphinidin inhibits neovascularisation in vivo in chorioallantoic membrane model.
Delphinidin overcomes in vitro and in vivo angiogenesis and thus appears promising for the development of an anti-angiogenic therapy.
流行病学研究表明，富含水果和蔬菜的饮食对癌症和心血管疾病具有有益的预防作用。尽管有证据表明食物中的多酚类化合物可能有一定益处，但这些有益作用的机制尚不清楚。本研究的目的是确定花青素类血管活性多酚化合物飞燕草素对内皮细胞增殖、迁移以及体内血管生成的影响。
飞燕草素可有效抑制血管内皮生长因子刺激的人脐内皮细胞迁移和增殖。流式细胞仪分析表明，飞燕草素对增殖的抑制作用与细胞周期在G(0)/G(1)期的阻滞相关。蛋白质免疫印迹分析显示，飞燕草素可逆转血管内皮生长因子诱导的细胞周期蛋白依赖性激酶抑制剂p27(kip1)表达降低以及血管内皮生长因子诱导的细胞周期蛋白D1和细胞周期蛋白A表达增加，而这两者都是实现G(1)期到S期转变所必需的。此外，飞燕草素在鸡胚绒毛尿囊膜模型中可抑制体内新血管形成。
飞燕草素可克服体外和体内的血管生成，因此在抗血管生成治疗的开发方面似乎很有前景。
