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/Rtreated 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. K E Y W O R D S apoptosis, neonatal hypoxic-ischemic encephalopathy, oxidative stress, PI3K/Akt/mTOR signaling pathway, platycodin D
| INTRODUCTIONNeonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death in infants, which is caused by hypoxic-ischemic injury to the developing brain during the perinatal period. 1 Neonatal HIE usually results in cerebral palsy, epilepsy, and motor-cognitive deficits in later life. 2 To date, clinical therapy for neonatal HIE is limited; hypothermia is an advanced treatment that can improve motor outcomes. 2,3 However, the hypothermia therapy is only effective in 40% to 50% of patients and infants may still have obvious cognitive or communication problems. 2 The infants who experience HIE will require significant medical input throughout life, which may result in damage to their quality of life and heavy financial burden to the family. 2 Therefore, it is