The neuroprotective effects of paeoniflorin against MPP+-induced damage to dopaminergic neurons via the Akt/Nrf2/GPX4 pathway

Paeoniflorin (PF), a water-soluble monoterpene glycoside extracted from the root of Paeonia lactiflora Pall, has been shown to exert neuroprotective effects against neurodegenerative diseases such as Parkinson’s disease (PD). However, its underlying mechanisms remain unknown. Our results showed that at certain concentrations, PF alleviated 1-methyl-4-phenylpyridinium (MPP+)-induced morphological damage and inhibited neuronal ferroptosis. Moreover, our research indicated that the neuroprotective effect of PF could be partially blocked by ML385 (a nuclear factor erythroid-2-related factor 2 (Nrf2) inhibitor) and LY29400 (an Akt inhibitor). These findings suggest that PF protects against MPP+-induced neurotoxicity by preventing ferroptosis via activation of the Akt/Nrf2/Gpx4 pathway in vitro. •This is the first study to investigate paeoniflorin’s neuroprotective effects against MPP+-induced damage to dopaminergic neurons via anti-ferroptosis pathway.•Paeoniflorin improves GPX4 expression via the Akt/Nrf2/GPX4 pathway at a low concentration.•PF is not toxic at a lower concentration while PF causes toxic damage to primary dopaminergic neurons at a high concentration.