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: Young-Whan Choi, Hyo Jin Kim, Sung-Sam Park, Jae-Heun Chung, Hee-Woo Lee, Sae-Ock Oh, Bong-Seon Kim, Jae-Bong Kim, Hae-Young Chung, Byung-Pal Yu, Chi-Dae Kim, Sik Yoon
• Journal: Vascular pharmacology (Vascul Pharmacol) Vol. 51 Issue 4 Pg. 215-24 (Oct 2009) ISSN: 1879-3649 [Electronic] United States
• PMID: 19539051 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Inflammation Mediators
• Plant Extracts
• Reactive Oxygen Species
• Sesquiterpenes
• Vascular Cell Adhesion Molecule-1
• alpha-iso-cubebene

Topics

• Anti-Inflammatory Agents, Non-Steroidal (isolation & purification, pharmacology)
• Cell Adhesion (drug effects, physiology)
• Cell Survival (drug effects, physiology)
• Cells, Cultured
• Endothelium, Vascular (cytology, drug effects, physiology)
• Humans
• Inflammation Mediators (isolation & purification, pharmacology)
• Plant Extracts (isolation & purification, pharmacology)
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Schisandra
• Sesquiterpenes (isolation & purification, pharmacology)
• Vascular Cell Adhesion Molecule-1 (biosynthesis)