Paeonol suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-kappaB signaling pathways.
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.
Nizamutdinova
Irina Tsoy
IT
Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
Oh
Hwa Min
HM
Min
Young Nam
YN
Park
Sun Hee
SH
Lee
Min Joo
MJ
Kim
Ju Sun
JS
Yean
Min Hye
MH
Kang
Sam Sik
SS
Kim
Yeong Shik
YS
Chang
Ki Churl
KC
Kim
Hye Jung
HJ
D000098:Acetophenones / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis* / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000098:Acetophenones; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C013638:paeonol; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases