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

Eur J Pharmacol. 2005 Apr 18;513(1-2):1-8. doi: 10.1016/j.ejphar.2005.01.059.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzaldehydes / pharmacology*
  • Blotting, Western
  • Catechols / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line
  • Dose-Response Relationship, Drug
  • E-Selectin / genetics
  • E-Selectin / metabolism
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Gene Expression / drug effects
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / metabolism
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor AP-1 / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • U937 Cells
  • Umbilical Veins / cytology
  • Vascular Cell Adhesion Molecule-1 / genetics*
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Benzaldehydes
  • Catechols
  • E-Selectin
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • protocatechualdehyde