Involvement of heme oxygenase-1 induction in anti-vascular inflammation effects of Xanthoceras sorbifolia in human umbilical vein endothelial cells

Abstract 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-κB) 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-acetyl-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-κB/ROS pathway and activation of the Nrf-2/HO-1 pathway.