Treatment of endothelial cell with flavonoids modulates transendothelial leukocyte migration

Abstract

Objective: This study aimed to investigate the influence of the flavonoid oxerutin (Venoruton®, Novartis, Basel, Switzerland) on endothelial cell apoptosis and transendothelial migration of peripheral blood mononuclear cells and to elucidate the potential mechanisms affecting these processes. Methods: Human endothelial cells were treated with Venoruton to assess the potential effect on apoptosis and on the transendothelial migration process. Endothelial nitric oxide synthase and inducible nitric oxide synthase expression in endothelial cell after Venoruton treatment as well as reactive oxygen species levels were analyzed. Results: Low-dose Venoruton shows a protective effect on endothelial cells and inhibits transendothelial migration of peripheral blood mononuclear cells through an endothelial monolayer, but high-dose Venoruton inversely elevated transendothelial migration of peripheral blood mononuclear cells. Meanwhile, a dose-dependent action of Venoruton on endothelial cell apoptosis could be observed. Endothelial nitric oxide synthase and inducible nitric oxide synthase expression were gradually increased in endothelial cells with increasing Venoruton dosage. In addition, reactive oxygen species were significantly reduced by 0.1 mM and 0.5 mM Venoruton and elevated after high dose treatment. Conclusion: These data suggest that the increased transendothelial migration of peripheral blood mononuclear cells is related to the excessive activation of the nitric oxide-axis and subsequent relaxation of the endothelial cells.