Voacangine protects hippocampal neuronal cells against oxygen–glucose deprivation/reoxygenation‐caused oxidative stress and ferroptosis by activating the PI3K‐Akt‐FoxO signaling

Abstract

AbstractVoacangine, a naturally occurring alkaloid, has been testified to display beneficial effects on a variety of human diseases, but its role in ischemic stroke is unclear. The impacts of voacangine on oxygen–glucose deprivation/reoxygenation (OGD/R)‐tempted hippocampal neuronal cells are investigated. The bioinformatics analysis found that voacangine is a bioactive ingredient that may have good effects on ischemic stroke. KEGG pathways analysis found that voacangine may regulate ischemic stroke through modulating the PI3K‐Akt‐FoxO signaling pathway. Voacangine could mitigate OGD/R‐tempted cytotoxicity in HT22 cells. Voacangine mitigated OGD/R‐tempted oxidative stress in HT22 cells by diminishing reactive oxygen species level and enhancing superoxide dismutase level. Voacangine mitigated OGD/R‐tempted ferroptosis in HT22 cells. Voacangine promoted activation of the PI3K‐Akt‐FoxO signaling in OGD/R‐induced HT22 cells. Inactivation of the PI3K‐Akt‐FoxO signaling pathway reversed the protective effects of voacangine against OGD/R‐tempted oxidative stress, cytotoxicity, and ferroptosis in HT22 cells. In conclusion, voacangine protects hippocampal neuronal cells against OGD/R‐caused oxidative stress and ferroptosis by activating the PI3K‐Akt‐FoxO signaling.