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

ABSTRACT

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).

GRAPHICAL ABSTRACT

KEYWORDS:

• Neuroprotection, neurodegenerative diseases
• olive oil phenolic compounds
• oxidative stress
• superoxide anion radical, cyclic voltammetry

Acknowledgements

We are very grateful to Sophie Tomasi for reading and discussion and to Xuan Mai DO, Solenn Ferron and Aurelie Sauvager for their technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Chaire Louise & André Charron on Alzheimer’s disease, Institute of nutrition and functional food (INAF), NSERC, FQRNT, Fondation Armand-Frappier, Region Bretagne (ARED grant, LICHALZH No 8964).

Notes on contributors

Morgane Lambert de Malezieu

Morgane Lambert de Malezieu is a four-year PhD student in biology and electrochemistry. Her main research interests centers on how diet component could act in a neuronal context to prevent or reverse deleterious effect of oxidative insults. She is also concerned about the burden of oxidative stress on aging and chronic diseases, especially on development of neurodegenerative diseases like Alzheimer’s or Parkinson’s diseases. For her M.A. in France, she chose to study the field of nutraceuticals engineering to understand the health beneficial effects of an accurate micronutritional diet using natural phytochemical extracts. For her Thesis, she is working under the supervision of Marie-Laurence Abasq, Sophie Tomasi and Charles Ramassamy, in cotutelle between two universities. Her project was to understand how a combination of phenolic compounds from Mediterranean diet could emphasize their helpful effects to inhibit or delay the oxidative stress-induced neuronal death leading to cognitive decline.

Patricia Courtel

Patricia Courtel has been a technician at the University of Rennes for 1996. After few years in the synthesis field of sulfur compounds, she built up skills in electrochemistry to study natural products. She joined the ISCR (Institut des Sciences Chimiques de Rennes) in 2010. She is also in charge of the analytical practical training room at the Faculty of Pharmacy.

Lekha Sleno

Lekha Sleno received her PhD in Chemistry in 2006 from Dalhousie University in Halifax, NS, Canada, under the supervision of Dr Dietrich Volmer (NRC). She then went on to two post-doctoral internships of one year each at the University of Geneva (with Gerard Hopfgartner) and University of Toronto (with Andrew Emili). In 2008, she became Assistant Professor in the chemistry department at the University of Quebec at Montreal (UQAM). She is now Full Professor and holds a Strategic UQAM Chair in Bioanalytical Chemistry. Her expertise is in bioanalytical mass spectrometry for the development of methods in proteomics and metabolomics.

Marie-Laurence Abasq

Marie Laurence Abasq received her PhD in Chemistry in 1994 at the University of Brest (France) under the supervision of Dr J. Talarmin, Pr. F.Y. Pétillon (CNRS 6521) and of Pr C.J. Pickett, University of Sussex (G.B.), Unit of Nitrogen Fixation, where she completed a 6-month intership. After a postdoctoral position (Elf Atochem employment contract) in Pr. A. Shaver team at McGill University (Canada), she became lecturer in 1996 at the University of Rennes (France). She joined the ISCR (Institut des Sciences Chimiques de Rennes, CNRS 6226) in 2010. She possesses skills in the field of electrochemistry and her current research interests focus on studying the physicochemical properties of natural bioactive molecules.

Charles Ramassamy

Charles Ramassamy is Professor of Pharmacology at the University INRS-Institute Armand Frappier, a member of the Institute of Nutrition and Functional Foods (INAF, University Laval). He received his Ph.D from the University of Rouen in France and completed his post-doctoral at the Douglas Hospital Research Center at McGill University in Canada. Dr. Ramassamy is a chair holder of the Louise & André Charron in Alzheimer’s Disease, and one of the leading expert in the role of oxidative stress in aging and in the pathophysiology and identification of biomarkers in Alzheimer’s Disease. In parallel, his laboratory investigates the neuroprotective of some natural compounds such as polyphenols present in diet and in natural extracts. His objective is to identify polyphenols with neuroprotective activity. At long term, these compounds could be useful in the prevention and treatment of some neurodegenerative disorders. Using an interdisciplinary approach, his laboratory also investigates the development of new nanoneuropharmacological tools based on polymeric biocompatible and biodegradable nanoparticles to enhance the bioavailability and the efficacy of pharmacological drugs in the brain.