Monoterpene-rich essential oil from <i>Artemisia santonicum</i> L. exerts neuroprotective effects in Aβ-induced SH-SY5Y cells: Modulation of tau pathology, neuroinflammation, oxidative stress, and synaptic-metabolic pathways

Understanding the complex biological mechanisms of ad requires innovative treatment approaches for this disease. In this context, natural compounds, especially monoterpenes, attract attention with their potential for biological activity. In this study, the therapeutic potential of monoterpene rich essential oil obtained from <i>Artemisia santonicum</i> L. for the treatment of ad was comprehensively evaluated. GC-MS analysis showed that the major monoterpenes were limonene, camphor, pinene, terpineol, and carvone in essential oil obtained from <i>A. santonicum</i> L. Possible common targets of monoterpenes with ad were predicted and their PPI networks were analyzed. Furthermore, gene set enrichment analysis was applied to understand the functional roles of these possible common targets and their relationships with biological pathways. Molecular docking studies revealed the binding affinities and interaction abilities of monoterpenes with the predicted possible common targets. The monoterpene rich essential oil obtained from <i>A. santonicum</i> L. used in our study provides a neuroprotective effect by targeting the pathological mechanisms of ad. We designed <i>in vitro</i> experiments to elucidate the mechanism of the mentioned neuroprotective effect. Within the scope of the study, neuroprotective effect analyses were performed to evaluate cell viability rates and <i>in vitro</i> AChE enzyme activity, while the ELISA method was used to determine phosphorylated tau levels and to assess neuroinflammatory responses. In addition, apoptosis levels, MMP changes and intracellular ROS accumulation were examined by flow cytometry analyses. These comprehensive analyses aimed to reveal the molecular mechanisms of the neuroprotective effect of monoterpene rich essential oil obtained from <i>A. santonicum</i> L. and to shed light on its potential therapeutic applications in ad.