Paeonol suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-α-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-κB signaling pathways

• DOI: 10.1016/j.intimp.2006.11.004
• Publication Date: 2006-12-15T12:27:38Z
• Authors: Irina Tsoy Nizamu...; Hwa Min Oh; Young Nam Min; Sun Hee Park; Min Joo Lee; Ju Sun Kim; Min Hye Yean; Sam Sik Kang; Yeong Shik Kim; Ki Churl Chang; Hye Jung Kim
• Keywords: Umbilical Veins; 0303 health sciences; Tumor Necrosis Factor-alpha; NF-kappa B; Acetophenones; Endothelial Cells; Atherosclerosis; Intercellular Adhesion Molecule-1; p38 Mitogen-Activated Protein Kinases; 3. Good health; Enzyme Activation; 03 medical and health sciences; NF-KappaB Inhibitor alpha; Cell Adhesion; Humans; I-kappa B Proteins; Phosphorylation; Extracellular Signal-Regulated MAP Kinases; Cells, Cultured; Signal Transduction

Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of the traditionally used Chinese herb Paeonia lactiflora Pallas, has anti-inflammatory, antioxidant and cardiovascular protective activities. We studied how the levels of intercellular adhesion molecule-1 (ICAM-1), one of the key molecules in the development of atherosclerosis, might be affected by paeonol in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs). Paeonol concentration-dependently inhibited the production of ICAM-1; it inhibited nuclear factor-kappaB (NF-kappaB) p65 translocation into the nucleus and the phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also blocked the TNF-alpha-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK), which are involved in regulating ICAM-1 production by TNF-alpha. Paeonol inhibited U937 monocyte adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of monocytes to endothelium by regulating the production of critical adhesion molecules by TNF-alpha. The inhibitory effect of paeonol on ICAM-1 production might be mediated by inhibiting p38, ERK and NF-kappaB signaling pathways, which are involved in TNF-alpha-induced ICAM-1 production. Thus, paeonol may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis.