Clematichinenoside inhibits VCAM-1 and ICAM-1 expression in TNF-α-treated endothelial cells via NADPH oxidase-dependent IκB kinase/NF-κB pathway

摘要: Proinflammatory cytokine TNF-α-induced adhesion of leukocytes to endothelial cells plays a critical role in the early stage atherosclerosis. Oxidative stress and redox-sensitive transcription factors are implicated process. Thus, compounds that mediate intracellular redox status regulate great therapeutic interest. Clematichinenoside (AR), triterpene saponin isolated from root Clematis chinensis Osbeck, was previously demonstrated have anti-inflammatory antioxidative properties. However, little is known about exact mechanism underlying these actions. Thus we performed detailed study on its effect leukocytes-endothelial with TNF-α-stimulated human umbilical vein (HUVECs) cell-free systems. First, found AR reduced VCAM-1 ICAM-1 expression their promoter activity, inhibited translocation p65 phosphorylation IκBα, suppressed IκB kinase-β (IKK-β) lowered O2(∙-) H2O2 levels, tackled p47(phox) translocation, decreased NOX4 NADPH oxidase expression. Second, showed exhibited no direct free radical scavenging ability systems at concentrations were used intact cells. Besides, had activity IKK-β extracted HUVECs. We also p47 expression, reactive oxygen species (ROS) levels up-regulated before Moreover, TNF-α-enhanced by (polyethylene glycol) PEG-catalase, N-acetylcysteine (NAC), vitamin E. In conclusion, results suggest reduces through oxidase-dependent IKK/NF-κB pathways HUVECs, which finally suppress monocyte-HUVECs adhesion. This compound potentially beneficial for early-stage