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

作者:Jiaxi Song, Junping Kou, Ya-Lin Huang, Boyang Yu · 发表于:Journal of Pharmacological Sciences · 年份:2010 · DOI:10.1254/jphs.10076sc · 被引用次数:15 · 研究领域:NF-κB Signaling Pathways、Phytochemistry and Bioactive Compounds、Phytochemical Studies and Bioactivities

Our previous results suggested that ruscogenin inhibited tumor necrosis factor alpha (TNF-alpha)-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-alpha in human umbilical vein endothelial cells (HUVECs). The results showed that ruscogenin significantly suppressed p65 phosphorylation, IkappaB-alpha phosphorylation and degradation, and inhibited IkappaB kinase alpha (IKKalpha) and IKKbeta activation induced by TNF-alpha. However, it exerted weak effects on TNF-alpha-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-kappaB (NF-kappaB), but not by mitogen-activated protein kinase (MAPK) and Akt signaling pathways.