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

Abstract

Antioxidant therapy is considered as promising strategy for treating oxidative stress-induced cardiovascular disease. Bis (β-elemene-13-yl) glutarate (BEG) is a novel β-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 μmol/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 mM H₂O₂. 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.

Keywords: Antioxidant activity; Bis (β-elemene-13-yl) glutarate; Endothelial nitric oxide synthase; Nitric oxide; Reactive oxygen species; Vascular endothelial cells.