Platycodin D protects cortical neurons against oxygen-glucose deprivation/reperfusion in neonatal hypoxic-ischemic encephalopathy.

Abstract

Neonatal hypoxic-ischemic encephalopathy is one of the leading causes of death in infants. Increasing evidence indicates that oxidative stress and apoptosis are major contributors to hypoxic-ischemic injury and can be used as particularly promising therapeutic targets. Platycodin D (PLD) is a triterpenoid saponin that exhibits antioxidant properties. The aim of this study was to evaluate the effects of PLD on hypoxic-ischemic injury in primary cortical neurons. We found that oxygen-glucose deprivation/reperfusion (OGD/R) induced inhibition of cell viability and cytotoxicity, which were attenuated by PLD treatment. PLD treatment inhibited oxidative stress induced by OGD/R, which was evidenced by the reduced level of reactive oxygen species and increased activities of catalase, superoxide dismutase, and glutathione peroxidase. Histone-DNA enzyme-linked immunosorbent assay revealed that apoptosis was significantly decreased after PLD treatment in OGD/R-treated cortical neurons. The increased bax expression and decreased bcl-2 expression induced by OGD/R were reversed by PLD treatment. Furthermore, PLD treatment caused the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in OGD/R-stimulated cortical neurons. Suppression of this pathway blocked the protective effects of PLD on OGD/R-induced cell injury. These findings suggested that PLD executes its protective effects on OGD/R-induced cell injury via regulating the PI3K/Akt/mTOR pathway in cortical neurons.