Paeoniflorin attenuates oxidative stress injury and improves mitochondrial membrane potential in human EA.hy926 endothelial cell through p-eIF2α and CHOP signaling

Abstract

Endothelium injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of cardiovascular disorders. Paeoniflorin (PF) has shown good antioxidant properties. The present study investigated the effect of PF on oxidative damage of EA.hy926 cells and elucidated its underlying molecular mechanisms. The results revealed that PF pretreatment increased cell viability, inhibited the activation of caspase- 3, Bax/Bcl2 ratio, and suppressed ROS accumulation during hydrogen peroxide (H2O2)- induced oxidative stress in EA.hy926 cells. Moreover, the PF restored ER stress-related apoptosis via loss of mitochondrial membrane potential (Δψm) and diminished intracellular Ca2+ evoked by H2O2. In addition, H2O2 induced ER stress was attenuated by PF via down-regulation the p-eIF2α and CHOP, and up regulation cyclophyllinD in EA.hy926 cells. In conclusion, our study demonstrates a pivotal role of PF in protecting against H2O2 induced cytotoxicity via regulating CHOP/p-eIF2α pathway, and suggests the therapeutic values of PF against endothelial injury.

Keywords

• Paeoniflorin
• Human EA.hy926 endothelial cells
• Endoplasmic reticulum (ER) stress
• eIF2α
• CHOP
• Mitochondrial membrane potential (Δψm)