Protocatechuic aldehyde suppresses TNF-alpha-induced ICAM-1 and VCAM-1 expression in human umbilical vein endothelial cells.

Adhesion molecules, which play a crucial role in the development of atherogenesis, are produced by endothelial cells following stimulation with various inflammatory cytokines. The current studies examined the effect of a potent water-soluble antioxidant, protocatechuic aldehyde (derived from the Chinese herb, Salvia miltiorrhiza), on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-alpha (TNF-alpha). Protocatechuic aldehyde appeared to specifically downregulate the TNF-alpha-induced cell surface expression of vascular adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) on HUVECs as well as the release of soluble VCAM-1and ICAM-1 from HUVECs in a dose-response manner at pharmacologically relevant concentrations (0.15-1.35 mM). We also observed a dose-dependent lowering of mRNA expression of VCAM-1 and ICAM-1 in the presence of protocatechuic aldehyde. Furthermore, protocatechuic aldehyde (0.15, 0.45, and 1.35 mM) notably inhibited TNF-alpha-induced upregulation of U937 cell adhesion to HUVECs to 83.7%, 60.9%, and 40.8%, respectively. A gel shift assay further showed that protocatechuic aldehyde inhibited the TNF-alpha-activated NF-kappaB and AP-1 DNA binding activities in a dose-dependent manner. Collectively, these results indicate that protocatechuic aldehyde inhibits TNF-alpha-stimulated VCAM-1 and ICAM-1expression in HUVECs through a mechanism that involves NF-kappaB and AP-1.