Hydroxytyrosol Inhibits BPS‐Induced NF‐κB Signaling Pathway Activation, Mitigates Oxidative Stress, and Reduces Neuronal Apoptosis

Hydroxytyrosol (HT), a primary phenolic compound in olive oil, exhibits antioxidant and antiapoptotic effects in various cell types, including cardiomyocytes and human umbilical vein endothelial cells. Contrastingly, bisphenol S (BPS) is known to induce apoptosis in myocardial and endothelial cells via oxidative stress. BPS increases reactive oxygen species (ROS) production and reduces the viability of hippocampal HT22 cells. In this study, we explored whether HT could protect neurons from BPS-induced oxidative stress and apoptosis. Our results showed that HT effectively inhibited oxidative stress responses in the brains of BPS-treated mice and significantly decreased ROS production in BPS-treated HT22 and PC12 cells. Additionally, HT reduced BPS-induced neuronal apoptosis in the cortical regions of mice as well as in HT22 and PC12 cells. Further analysis revealed that BPS activates the NF-κB signaling pathway, a key mediator of oxidative stress and neuronal apoptosis, while HT counteracted these effects. In summary, this study demonstrates the antioxidant and antiapoptotic properties of HT in BPS-exposed neurons. These findings provide compelling experimental evidence supporting the potential dietary inclusion of HT-rich compounds to alleviate oxidative stress-related neuronal damage.