Ruscogenin Mainly Inhibits Nuclear Factor-κB but Not Akt and Mitogen-Activated Protein Kinase Signaling Pathways in Human Umbilical Vein Endothelial Cells

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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.