Magnolia officinalis (L.) Bark Extract Counteracts Oxidative Brain Injury: A Proteomic Investigation into Neuroprotective Mechanisms

Neurodegenerative diseases involve progressive neuronal loss associated with oxidative stress (OS) and inflammation. Given the limited efficacy of current therapies, natural compounds with multitarget neuroprotective potential are of growing interest. In this study, we investigated the neuroprotective effects of a standardized Magnolia officinalis (L.) bark extract (MOE) in rat brain cortical slices exposed to hydrogen peroxide-induced OS. MOE significantly recovered tissue viability and reduced ROS and malondialdehyde levels caused by OS while attenuating caspase-3, -8, and -9 activation, suggesting modulation of intrinsic and extrinsic apoptotic pathways. Shotgun proteomics using LC-HRMS/MS identified OS-induced protein expression changes reversed by MOE, with fourteen of thirty-three altered proteins rescued by MOE co-treatment. These proteins participate in several processes, including neuronal survival, OS response, and proteostasis. Bioinformatic analysis demonstrated that genes responsible for protein synthesis regulated by MOE are subjected to transcriptional regulation by factors associated with OS, including FOXO4, NRF2, and SP1. The present findings support the hypothesis that MOE exerts multitarget neuroprotective effects by modulating key proteins involved in OS responses and neuronal survival in an acute ex vivo oxidative injury model, suggesting potential relevance for mechanisms associated with NDs.