Cynandione A inhibits lipopolysaccharide-induced cell adhesion via suppression of the protein expression of VCAM-1 in human endothelial cells

Cynandione A (CA) is one of the most active compounds in the roots of Cynanchum wilfordii, the extracts of which have been used extensively in East Asia to treat various diseases including anti-ischemic stroke. In the present study, the anti-adherent activity of CA in lipopolysaccharide (LPS)-stimulated human umbilical vascular endothelial cells (HUVECs) was investigated. CA markedly reduced the expression of vascular adhesion molecule-1 (VCAM-1) by LPS in HUVECs. The results also demonstrated that CA significantly reduced the expression of pro-inflammatory and chemoattractant cytokines, including interleukin (IL)-1 beta, IL-6, IL-8, monocyte chemoattractant protein-1 and tumor necrosis factor-alpha, in LPS-activated human endothelial cells. CA inhibited the phosphorylation of mitogen-activated protein kinases, including the extracellular signal-regulated kinase 1/2 and p38 kinases. It was found that CA decreased the IKK/I kappa B-alpha phosphorylation of inhibitor of nuclear factor (NF)-kappa B kinase/inhibitor of NF-kappa B-alpha, suppressed translocation of the NF-kappa B p65 subunit into the nucleus and inhibited the transcriptional activity of NF-kappa B. CA also decreased human monocyte cell adhesion to endothelial cells in LPS-stimulated conditions. These results demonstrated that CA inhibited the protein expression of VCAM-1 and pro-inflammatory cytokines by suppressing the transcriptional activity of NF-kappa B. The results also suggested that CA may be important in the development of anti-inflammatory drugs by inhibiting the expression of cell adhesion molecules.