Cynandione A inhibits lipopolysaccharide-induced cell adhesion via suppression of the protein expression of VCAM­1 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 anti­ischemic stroke. In the present study, the anti­adherent activity of CA in lipopolysaccharide (LPS)­stimulated human umbilical vascular endothelial cells (HUVECs) was investigated. CA markedly reduced the expression of vascular adhesion molecule­1 (VCAM­1) by LPS in HUVECs. The results also demonstrated that CA significantly reduced the expression of pro­inflammatory and chemoattractant cytokines, including interleukin (IL)­1ß, IL­6, IL­8, monocyte chemoattractant protein­1 and tumor necrosis factor­α, in LPS­activated human endothelial cells. CA inhibited the phosphorylation of mitogen­activated protein kinases, including the extracellular signal­regulated kinase 1/2 and p38 kinases. It was found that CA decreased the IKK/IκB­α phosphorylation of inhibitor of nuclear factor (NF)­κB kinase/inhibitor of NF­κB­α, suppressed translocation of the NF­κB p65 subunit into the nucleus and inhibited the transcriptional activity of NF­κB. CA also decreased human monocyte cell adhesion to endothelial cells in LPS­stimulated conditions. These results demonstrated that CA inhibited the protein expression of VCAM­1 and pro­inflammatory cytokines by suppressing the transcriptional activity of NF­κB. The results also suggested that CA may be important in the development of anti­inflammatory drugs by inhibiting the expression of cell adhesion molecules.