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

Voacangine, 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. Voacangine has been shown to have beneficial effects on several human diseases, but its role in ischemic stroke has not been elucidated. In this study, we have identified the neuroprotective effects of voacangine against oxygen‐glucose deprivation/reoxygenation (OGD/R)‐induced damage through bioinformatics and in vitro cell experiments. Mechanistically, voacangine protected hippocampal neuronal cells against OGD/R‐caused oxidative stress and ferroptosis by activating the PI3K‐Akt‐FoxO signaling. [ABSTRACT FROM AUTHOR]