The protective effects of a novel synthetic β-elemene derivative on human umbilical vein endothelial cells against oxidative stress-induced injury: Involvement of antioxidation and PI3k/Akt/eNOS/NO signaling pathways

Antioxidant therapy is considered as promising strategy for treating oxidative stress-induced cardiovascular disease. Bis (beta-elemene-13-yl) glutarate (BEG) is a novel beta-elemene derivative. Herein, we examined the antioxidant activity of BEG on human umbilical vein endothelial cells (HUVECs) after injury with hydrogen peroxide (H2O2) and investigated the mechanism involved. HUVECs were divided into the following groups: control group (untreated cells); treated groups (cells treated with 0.1, 1, 10 mu mol/L of BEG); positive control group (cells treated with 0.1 mM Vitamin E); model group (cells treated with 0.5 mM H2O2 alone). Cells were pre-incubated with or without BEG for 24 h and then incubated for a further 2 h with 0.5 mMH(2)O(2). Our results showed that BEG significantly reduced H2O2 induced loss in endothelial cell viability, reactive oxygen species (ROS) production, reduced lactate dehydrogenase (LDH) release, and malonyldialdehyde (MDA) level in a concentration-dependent manner. Also, BEG increased the cellular the superoxide dismutase (SOD) activity. Moreover, we found that H2O2 decreased Akt and eNOS phosphorylation, which perhaps, indirectly reduced nitric oxide (NO) production. These effects induced by H2O2, however, were reduced by pre-treatment with BEG. BEG effects were inhibited by a PI3K inhibitor (wortmannin) and eNOS inhibitor (L-NAME). In conclusion, the present study demonstrated that BEG has antioxidant activity. Furthermore, BEG reduced H2O2-induced endothelial cells injury by the involvement of antioxidation and PI3K/Akt/eNOS/NO signaling pathways.