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).

UV-Vis Spectroelectrochemistry of Oleuropein, Tyrosol, and p-Coumaric Acid Individually and in an Equimolar Combination. Differences in LC-ESI-MS2 Profiles of Oxidation Products and their Neuroprotective Properties.

Major phenolic compounds from olive oil (ArOH-EVOO), oleuropein (Ole), tyrosol (Tyr), and p-coumaric acid (p-Cou), are known for their antioxidant and neuroprotective properties. We previously demonstrated that their combination could potentiate their antioxidant activity in vitro and in cellulo. To further our knowledge of their electron-transfer properties, Ole, Tyr, and p-Cou underwent a spectroelectrochemical study, performed either individually or in equimolar mixtures. Two mixtures (Mix and Mix-seq) were prepared in order to determine whether distinct molecules could arise from their simultaneous or sequential oxidation. The comparison of Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (LC-ESI-MS2) profiles highlighted the presence of specific oxidized products found in the mixes. We hypothesized that they derived from the dimerization between Tyr and Ole or p-Cou, which have reacted either in their native or oxidized forms. Moreover, Ole regenerates when the Mix undergoes oxidation. Our study also showed significant neuroprotection by oxidized Ole and oxidized Mix against H2O2 toxicity on SK-N-SH cells, after 24 h of treatment with very low concentrations (1 and 5 nM). This suggests the putative relevant role of oxidized Ole products to protect or delay neuronal death.