Inhibition of endothelial cell adhesion by the new anti-inflammatory agent α-iso-cubebene

Abstract

The current study explored if α-iso-cubebene, a novel cubebene sesquiterpene compound purified from Schisandra chinensis, could attenuate the activities of adhesion molecules in tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). The study was performed on HUVECs that were pretreated with 25 μg/ml of α-iso-cubebene before TNF-α treatment. Treatment of HUVECs with α-iso-cubebene for 6 h significantly inhibited TNF-α-induced reactive oxygen species (ROS) formation. HUVECs treated with α-iso-cubebene showed markedly suppressed TNF-α-induced mRNA expression of VCAM-1 and E-selectin, but little alteration in ICAM-1 mRNA expression. α-iso-Cubebene treatment also significantly decreased the TNF-α-induced cell surface and total protein expression of VCAM-1 and E-selectin without affecting ICAM-1 expression. In addition, treatment of HUVECs with α-iso-cubebene markedly reduced U937 monocyte adhesion to TNF-α-stimulated HUVECs. α-iso-Cubebene treatment did not affect translocation of NF-κB transcription factor from the cytosol into the nucleus. However, α-iso-cubebene significantly inhibited NF-κB transcription factor activation in TNF-α-stimulated HUVECs. The new anti-inflammatory agent α-iso-cubebene attenuates TNF-α-stimulated endothelial adhesion to monocytes by inhibiting intracellular ROS production, the activation of redox-sensitive NF-κB transcription factor and expression of VCAM-1 and E-selectin. Based on these findings, α-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.