OBJECTIVE:To define the effects of Xanthoceras sorbifolia (EXS) on vascular inflammation and the mechanisms in endothelial cells.METHODS:Vascular protective effects of an ethanol extract of seeds from EXS (1-50 μg/mL) against tumor necrosis factor-α (TNF-α)-induced vascular inflammation were examined in human umbilical vein endothelial cells (HUVECs).RESULTS:EXS significantly decreased TNF-α-induced expression of cell adhesion molecules,such as intracellular adhesion molecule-1,vascular cell adhesion molecule-1,and endothelial cell selectin,in a dose-dependent manner.Pre-treatment with EXS significantly inhibited translocation and transcriptional activity of nuclear factor-κB (NF-KB) increased by TNF-α.EXS also significantly inhibited formation of intracellular reactive oxygen species (ROS).Moreover,the vascular protective effects of EXS were linked to up-regulation of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf-2) expression.EXS-induced HO-1 expression was significantly decreased in SnPP (HO-1 inhibitor)-and HO-1 siRNA-treated cells,whereas an increase was found in cobalt protoporphyrin IX (CoPP) (HO-1 inducer)-treated cells.In addition,pretreatment with EXS increased HO-1 and Nrf-2 expression under TNF-α stimulation with or without N-acetyI-L-cysteine.Furthermore,the inhibitory effects of EXS on TNF-α-induced vascular inflammation were partially reversed in SnPP-and of HO-1 siRNA-treated cells but increased by CoPP.CONCLUSION:These results suggest that EXS may have important implications for prevention of vascular complications associated with vascular inflammation by inhibition of the NF-KB/ROS pathway and activation of the Nrf-2/HO-1 pathway.