title: Inhibition of endothelial cell adhesion by the new anti-inflammatory agent alpha-iso-cubebene.
abstract: The current study explored if alpha-iso-cubebene, a novel cubebene sesquiterpene compound purified from Schisandra chinensis, could attenuate the activities of adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs). The study was performed on HUVECs that were pretreated with 25 microg/ml of alpha-iso-cubebene before TNF-alpha treatment. Treatment of HUVECs with alpha-iso-cubebene for 6 h significantly inhibited TNF-alpha-induced reactive oxygen species (ROS) formation. HUVECs treated with alpha-iso-cubebene showed markedly suppressed TNF-alpha-induced mRNA expression of VCAM-1 and E-selectin, but little alteration in ICAM-1 mRNA expression. alpha-iso-Cubebene treatment also significantly decreased the TNF-alpha-induced cell surface and total protein expression of VCAM-1 and E-selectin without affecting ICAM-1 expression. In addition, treatment of HUVECs with alpha-iso-cubebene markedly reduced U937 monocyte adhesion to TNF-alpha-stimulated HUVECs. alpha-iso-Cubebene treatment did not affect translocation of NF-kappaB transcription factor from the cytosol into the nucleus. However, alpha-iso-cubebene significantly inhibited NF-kappaB transcription factor activation in TNF-alpha-stimulated HUVECs. The new anti-inflammatory agent alpha-iso-cubebene attenuates TNF-alpha-stimulated endothelial adhesion to monocytes by inhibiting intracellular ROS production, the activation of redox-sensitive NF-kappaB transcription factor and expression of VCAM-1 and E-selectin. Based on these findings, alpha-iso-cubebene is proposed as an effective new anti-inflammatory agent that may have a potential therapeutic use for the prevention and treatment of vascular diseases.
authors.affiliation: Department of Horticultural Bioscience, College of Natural Resources and Life Science, Pusan National University, Miryang, South Korea.
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Choi
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung-Sam
authors.initials: SS
authors.lastname: Park
authors.forename: Jae-Heun
authors.initials: JH
authors.lastname: Chung
authors.forename: Hee-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Sae-Ock
authors.initials: SO
authors.lastname: Oh
authors.forename: Bong-Seon
authors.initials: BS
authors.lastname: Kim
authors.forename: Jae-Bong
authors.initials: JB
authors.lastname: Kim
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Byung-Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Chi-Dae
authors.initials: CD
authors.lastname: Kim
authors.forename: Sik
authors.initials: S
authors.lastname: Yoon
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D032141:Schisandra; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D019010:Vascular Cell Adhesion Molecule-1; C539088:alpha-iso-cubebene