Synergistic properties of bioavailable phenolic compounds from olive oil: electron transfer and neuroprotective properties.

Phenolic compounds from olive oil (ArOH-EVOO) are recognized for their antioxidant and neuroprotective capacities, but are often studied individually or through a natural extract. As their reactivity towards reactive oxygen species (ROS) depends on their structure and could implicate different complementary mechanisms, we hypothesized that their effects could be enhanced by an innovative combination of some of the most abundant ArOH-EVOO. Using electrochemical methods, we have compared their reactivity towards hydrogen peroxide and the superoxide anion radical. The mixture containing oleuropein, p-coumaric acid and tyrosol (Mix1), was more efficient than the mixture containing hydroxytyrosol, the oleuropein catechol moiety, and the two monophenols (Mix2). On neuronal SK-N-SH cells challenged with H2O2 or Paraquat, low concentrations (0.1 and 1 µM) of the Mix1 improved neuronal survival. These neuroprotective effects were supported by a decrease in intracellular ROS, in the protein carbonyl levels and the prevention of the redox-sensitive factors Nrf2 and NF-κB activation. These intracellular effects were supported by the demonstration of the internalization of these ArOH-EVOO into neuronal cells, evidenced by LC-HRMS. Our results demonstrated that this combination of ArOH-EVOO could be more efficient than individual ArOH usually studied for their neuroprotective properties. These data suggest that the Mix1 could delay neuronal death in neurodegenerative diseases related to oxidative stress such as Alzheimer's (AD) and Parkinson's diseases (PD).