title: 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.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Irina Tsoy
authors.initials: IT
authors.lastname: Nizamutdinova
authors.forename: Hwa Min
authors.initials: HM
authors.lastname: Oh
authors.forename: Young Nam
authors.initials: YN
authors.lastname: Min
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Min Joo
authors.initials: MJ
authors.lastname: Lee
authors.forename: Ju Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Min Hye
authors.initials: MH
authors.lastname: Yean
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: 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
chemical_list: 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