Inhibition of endothelial cell adhesion by the new anti-inflammatory agent alpha-iso-cubebene.
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.
Choi
Young-Whan
YW
Department of Horticultural Bioscience, College of Natural Resources and Life Science, Pusan National University, Miryang, South Korea.
Kim
Hyo Jin
HJ
Park
Sung-Sam
SS
Chung
Jae-Heun
JH
Lee
Hee-Woo
HW
Oh
Sae-Ock
SO
Kim
Bong-Seon
BS
Kim
Jae-Bong
JB
Chung
Hae-Young
HY
Yu
Byung-Pal
BP
Kim
Chi-Dae
CD
Yoon
Sik
S
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
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