Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE’s ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model.

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

“…OL significantly decreased neuronal death. OL could also reduce the mitochondrial production of ROS resulting from blocking SOD activity [172] OL-aglycone…”

“…OL significantly decreased neuronal death. OL could also reduce the mitochondrial production of ROS resulting from blocking SOD activity [172] Antioxidants 2020, 9, 149 19 of 39 LDL oxidation and MPO activity, to reduce the expression of adhesion molecules, as angiotensin II production, and to confer protection to erythrocytes from oxidative hemolysis [33,73].…”

“…OL treatment significantly decreased neuronal death and reduced the mitochondrial production of ROS resulting from blocking superoxide dismutase activity. Moreover, the quantification of autophagy and acidic vesicles in the cytoplasm alongside the expression of specific autophagy markers uncovered a regulatory role for OL against autophagy flux impairment induced by bafilomycin A1 [171,172].…”

Phytochemical treatments target kynurenine pathway induced oxidative stress

“…In a Parkinson's cell model, Olea europaea, which contains, a phenolic compound called oleuropein, resisted oxidative stress caused by 6-hydroxydopamine and prevented neuronal death showing a decrease in neuronal death, Bax and Bcl-2 as apoptotic markers and superoxide (p < 0.05) [26]. Similarly, Ficus religiosa extract treated rats showed improved behaviour and reduced lipid peroxidation when treated with 6-hydroxydopamine [4].…”

Bioactivity of Olive Oil Phenols in Neuroprotection

“…A subsequent study evaluated the effect of picomolar doses of oleuropein on the modulation of autophagy in nerve growth factor (NGF)-differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA) [ 103 ]. Interestingly, the results of this study were in contrast with the results obtained by Rigacci et al, in fact oleuropein did not favor LC3-II accumulation and increased the protein level of p62, an indicator of inhibition of autophagy, suggesting that picomolar doses of oleuropein inhibit, rather than increase autophagy.…”