Ruscogenin mainly inhibits nuclear factor-kappaB 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 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.
Song
Jiaxi
J
Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, China.
Kou
Junping
J
Huang
Yalin
Y
Yu
Boyang
B
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013150:Spirostans / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D016328:NF-kappa B; D013150:Spirostans; C012541:ruscogenin; D051057:Proto-Oncogene Proteins c-akt