The Effect of Olive Leaf Methanolic Extract on Hippocampal Antioxidant Biomarkers in an Animal Model of Parkinson’s Disease

Document Type: Research Paper


Department of Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran


Background and Objective: Parkinson’s disease (PD) is a chronic neurodegenerative disease characterized by damages to striatal dopaminergic neurons that affects 1 to 2% of the population above 65 years of age. Olive leaf extract (OLE) is a powerful antioxidant that is considered as a source of various phenolic compounds. This study was conducted to evaluate the effects of methanolic OLE on hippocampal antioxidant biomarkers in an animal model of PD.
Materials and Methods: Intrastriatal 6-hydroxydopamine-lesioned rats were pretreated with OLE at doses of 50, 100 and 150 mg/kg/day for six weeks. At the end of treatment, the antioxidants activity in the hippocampal area was assayed.
Results: 6-hydroxydopamine–induced oxidative stress significantly decreased activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GRX) and catalase (CAT) and treatment with OLE restored the activity of antioxidant enzymes SOD, GPX, GRX, and CAT and also decreased malondialdehyde (MDA) as an index of lipid peroxidation and increased glutathione (GSH) levels in the hippocampus.
Conclusion: These results suggest that OLE pretreatment reduces hippocampal oxidative biomarkers in an animal model of PD.


1. Wang Y-H, Yu H-T, Pu X-P, Du G-H. Baicalein prevents 6-hydroxydopamine-induced mitochondrial dysfunction in SH-SY5Y cells via inhibition of mitochondrial oxidation and up-regulation of DJ-1 protein expression. Molecules. 2013;18(12):14726-38.
2. Castellani R, Smith M, Richey G, Perry G. Glycoxidation and oxidative stress in Parkinson disease and diffuse Lewy body disease. Brain Research. 1996;737(1):195-200.
3. Baluchnejadmojarad T, Jamali-Raeufy N, Zabihnejad S, Rabiee N, Roghani M. Troxerutin exerts neuroprotection in 6-hydroxydopamine lesion rat model of Parkinson’s disease: Possible involvement of PI3K/ERβ signaling. European Journal of Pharmacology. 2017;801:72-8.
4. Kiasalari Z, Baluchnejadmojarad T, Roghani M. Hypericum Perforatum Hydroalcoholic Extract Mitigates Motor Dysfunction and is Neuroprotective in Intrastriatal 6-Hydroxydopamine Rat Model of Parkinson’s Disease. Cellular and Molecular Neurobiology. 2016;36(4):521-30.
5. Kovacsova M, Barta A, Parohova J, Vrankova S, Pechanova O. Neuroprotective mechanisms of natural polyphenolic compounds. Activitas Nervosa Superior Rediviva. 2010;52(3):181-6.
6. Bayram B, Ozcelik B, Grimm S, Roeder T, Schrader C, Ernst IM, et al. A diet rich in olive oil phenolics reduces oxidative stress in the heart of SAMP8 mice by induction of Nrf2-dependent gene expression. Rejuvenation Research. 2012;15(1):71-81.
7. Omar SH. Oleuropein in olive and its pharmacological effects. Scientia Pharmaceutica. 2010;78(2):133-54.
8. Benavente-Garcıa O, Castillo J, Lorente J, Ortuno A, Del Rio J. Antioxidant activity of phenolics extracted from Olea europaea L. leaves. Food Chemistry. 2000;68(4):457-62.
9. Mohagheghi F, Bigdeli MR, Rasoulian B, Zeinanloo AA, Khoshbaten A. Dietary virgin olive oil reduces blood brain barrier permeability, brain edema, and brain injury in rats subjected to ischemia-reperfusion. The Scientific World Journal. 2010;10:1180-91.
10. Shen Y, Song SJ, Keum N, Park T. Olive leaf extract attenuates obesity in high-fat diet-fed mice by modulating the expression of molecules involved in adipogenesis and thermogenesis. Evidence-Based Complementary and Alternative Medicine. 2014;2014.
11. Rabiei Z, Bigdeli MR, Rasoulian B, Ghassempour A, Mirzajani F. The neuroprotection effect of pretreatment with olive leaf extract on brain lipidomics in rat stroke model. Phytomedicine. 2012;19(10):940-6.
12. Dewapriya P, Himaya S, Li Y-X, Kim S-K. Tyrosol exerts a protective effect against dopaminergic neuronal cell death in in vitro model of Parkinson’s disease. Food Chemistry. 2013;141(2):1147-57.
13. Mohagheghi F, Bigdeli MR, Rasoulian B, Hashemi P, Pour MR. The neuroprotective effect of olive leaf extract is related to improved blood–brain barrier permeability and brain edema in rat with experimental focal cerebral ischemia. Phytomedicine. 2011;18(2):170-5.
14. Khayyal MT, El-Ghazaly MA, Abdallah DM, Nassar NN, Okpanyi SN, Kreuter M-H. Blood Pressure Lowering Effect of an Olive Leaf Extract {Olea europaed) in L-NAME Induced Hypertension in Rats. Arzneimittelforschung. 2002;52(11):797-802.
15. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 2nd Ed., 1986, Academic Press, San Diego.
16. Shrivastava P, Vaibhav K, Tabassum R, Khan A, Ishrat T, Khan MM, et al. Anti-apoptotic and anti-inflammatory effect of Piperine on 6-OHDA induced Parkinson's rat model. The Journal of Nutritional Biochemistry. 2013;24(4):680-7.
17. Aghagolzadeh M. Olive leaf extract reverses the behavioral disruption and oxidative stress induced by intrastriatal injection of 6-hydroxydopamine in rats. Physiology and Pharmacology. 2017;21(1):44-53.
18. Xia E, Rao G, Van Remmen H, Heydari AR, Richardson A. Activities of antioxidant enzymes in various tissues of male Fischer 344 rats are altered by food restriction. The Journal of Nutrition. 1995;125(2):195.
19. sterbauer H, Cheeseman KH. [42] Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal. Methods in Enzymology. 1990;186:407-21.
20. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry. 1976;72(1-2):248-54.
21. Genet S, Kale RK, Baquer NZ. Alterations in antioxidant enzymes and oxidative damage in experimental diabetic rat tissues: effect of vanadate and fenugreek (Trigonella foenum graecum). Molecular and Cellular Biochemistry. 2002;236(1-2):7-12.
22. Sharma M, Gupta Y. Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sciences. 2002;71(21):2489-98.
23. Romero FJ, Romá J, Bosch-Morell F, Romero B, Segura-Aguilar J, Llombart-Bosch A, et al. Reduction of brain antioxidant defense upon treatment with butylated hydroxyanisole (BHA) and Sudan III in Syrian golden hamster. Neurochemical Research. 2000;25(3):389-93.
24. Alirezaei M, Rezaei M, Hajighahramani S, Sookhtehzari A, Kiani K. Oleuropein attenuates cognitive dysfunction and oxidative stress induced by some anesthetic drugs in the hippocampal area of rats. The Journal of Physiological Sciences. 2017;67(1):131-9.
25. Carito V, Ceccanti M, Cestari V, Natella F, Bello C, Coccurello R, et al. Olive polyphenol effects in a mouse model of chronic ethanol addiction. Nutrition. 2017;33:65-9.
26. Crespo MC, Tomé‐Carneiro J, Pintado C, Dávalos A, Visioli F, Burgos‐Ramos E. Hydroxytyrosol restores proper insulin signaling in an astrocytic model of Alzheimer's disease. BioFactors. 2017.
27. Lee O-H, Lee B-Y. Antioxidant and antimicrobial activities of individual and combined phenolics in Olea europaea leaf extract. Bioresource Technology. 2010;101(10):3751-4.