Ruscogenin mainly inhibits nuclear factor-κB but not Akt and mitogen-activated protein kinase signaling pathways in human umbilical vein endothelial cells

Our previous results suggested that ruscogenin inhibited tumor necrosis factor α (tnf-α)-induced leukocyte adhesion,which correlated with its suppression of intercellular adhesion molecule-1 (icam-1) expression in endothelial cells. in the present studies,we further examined its effects on the main signaling pathways involved in upregulation of icam-1 induced by tnf-α in human umbilical vein endothelial cells (huvecs). the results showed that ruscogenin significantly suppressed p65 phosphorylation,iκb-α phosphorylation and degradation,and inhibited iκb kinase α (ikkα) and ikkβ activation induced by tnf-α. however,it exerted weak effects on tnf-α-induced phosphorylations of p38,jnk,erk1/2,and akt. overall,our results indicated that downregulation of icam-1 expression by ruscogenin in huvecs might be mediated by nuclear factor-κb (nf-κb),but not by mitogen-activated protein kinase (mapk) and akt signaling pathways. © 2010 the japanese pharmacological society.