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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry


ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Research Article

Antioxidant Effects of Oleuropein on Hydrogen Peroxide-Induced Neuronal Stress- An In Vitro Study

Author(s): Altug Kucukgul*, Mehmet M. Isgor, Vesile Duzguner, Meryem N. Atabay and Azime Kucukgul

Volume 19, Issue 1, 2020

Page: [74 - 84] Pages: 11

DOI: 10.2174/1871523018666190201145824


Background: Persistent oxidative stress can lead to chronic inflammation and mediate most chronic diseases including neurological disorders. Oleuropein has been shown to be a potent antioxidant molecule in olive oil leaf having antioxidative properties.

Objective: The aim of this study was to investigate the protective effects of oleuropein against oxidative stress in human glioblastoma cells.

Methods: Human glioblastoma cells (U87) were pretreated with oleuropein (OP) essential oil 10 µM. After 30 minutes, 100 µM H2O2 was added to the cells for three hours. Cell survival was quantified by colorimetric MTT assay. Glutathione level, total oxidant capacity, total antioxidant capacity and nitric oxide levels were determined by using specific spectrophotometric methods. The relative gene expression level of iNOS was performed by qRT-PCR method.

Results: According to viability results, the effective concentration of H2O2 (100µM) significantly decreased cell viability and oleuropein pretreatment significantly prevented the cell losses. Oleuropein regenerated total antioxidant capacity and glutathione levels decreased by H2O2 exposure. In addition, nitric oxide and total oxidant capacity levels were also decreased after administration of oleuropein in treated cells.

Conclusion: Oleuropein was found to have potent antioxidative properties in human glioblastoma cells. However, further studies and validations are needed in order to understand the exact neuroprotective mechanism of oleuropein.

Keywords: Anti-inflammatory, anti-oxidant, glioblastoma, in vitro, neuroprotection, oleuropein.

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Panza, F.; Solfrizzi, V.; Colacicco, A.M.; D’Introno, A.; Capurso, C.; Torres, F.; Del Parigi, A.; Capurso, S.; Capurso, A. Mediterranean diet and cognitive decline. Public Health Nutr., 2004, 7(7), 959-963.
[] [PMID: 15482625]
Solfrizzi, V.; Panza, F.; Torres, F.; Mastroianni, F.; Del Parigi, A.; Venezia, A.; Capurso, A. High monounsaturated fatty acids intake protects against age-related cognitive decline. Neurology, 1999, 52(8), 1563-1569.
[] [PMID: 10331679]
Gikas, E.; Bazoti, F.N.; Tsarbopoulos, A. Conformation of oleuropein, the major bioactive compound of Oleaeuropea. J. Mol. Struct. Theochem, 2007, 821, 125-132.
Bisignano, G.; Tomaino, A.; Lo Cascio, R.; Crisafi, G.; Uccella, N.; Saija, A. On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol. J. Pharm. Pharmacol., 1999, 51(8), 971-974.
[] [PMID: 10504039]
Sanchez, J.C.; Alsina, M.A.; Herrlein, M.K.; Mestres, C. Interaction between the antibacterial compound, oleuropein, and model membranes. Colloid Polym. Sci., 2007, 285, 1351-1360.
Andreadou, I.; Sigala, F.; Iliodromitis, E.K.; Papaefthimiou, M.; Sigalas, C.; Aligiannis, N.; Savvari, P.; Gorgoulis, V.; Papalabros, E.; Kremastinos, D.T. Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress. J. Mol. Cell. Cardiol., 2007, 42(3), 549-558.
[] [PMID: 17223128]
Owen, R.W.; Giacosa, A.; Hull, W.E.; Haubner, R.; Würtele, G.; Spiegelhalder, B.; Bartsch, H. Olive-oil consumption and health: the possible role of antioxidants. Lancet Oncol., 2000, 1, 107-112.
[] [PMID: 11905662]
Visioli, F.; Bellosta, S.; Galli, C. Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages. Life Sci., 1998, 62(6), 541-546.
[] [PMID: 9464466]
Hamdi, H.K.; Castellon, R. Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor. Biochem. Biophys. Res. Commun., 2005, 334(3), 769-778.
[] [PMID: 16024000]
Micol, V.; Caturla, N.; Pérez-Fons, L.; Más, V.; Pérez, L.; Estepa, A. The olive leaf extract exhibits antiviral activity against viral haemorrhagic septicaemia rhabdovirus (VHSV). Antiviral Res., 2005, 66(2-3), 129-136.
[] [PMID: 15869811]
Lin, M.T.; Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006, 443(7113), 787-795.
[] [PMID: 17051205]
Visioli, F.; Galli, C. Biological properties of olive oil phytochemicals. Crit. Rev. Food Sci. Nutr., 2002, 42(3), 209-221.
[] [PMID: 12058980]
Hansen, M.B.; Nielsen, S.E.; Berg, K. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J. Immunol. Methods, 1989, 119(2), 203-210.
[] [PMID: 2470825]
Cortas, N.K.; Wakid, N.W. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin. Chem., 1990, 36(8 Pt 1), 1440-1443.
[] [PMID: 2387039]
Sedlak, J.; Lindsay, R.H. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal. Biochem., 1968, 25(1), 192-205.
[] [PMID: 4973948]
Crow, M.T.; Mani, K.; Nam, Y.J.; Kitsis, R.N. The mitochondrial death pathway and cardiac myocyte apoptosis. Circ. Res., 2004, 95(10), 957-970.
[] [PMID: 15539639]
Nakase, T.; Yamazaki, T.; Ogura, N.; Suzuki, A.; Nagata, K. The impact of inflammation on the pathogenesis and prognosis of ischemic stroke. J. Neurol. Sci., 2008, 271(1-2), 104-109.
[] [PMID: 18479710]
Floyd, R.A.; Hensley, K. Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiol. Aging, 2002, 23(5), 795-807.
[] [PMID: 12392783]
Yanishlieva, N.V.; Marinova, E.; Pokorný, J. Natural antioxidants from herbs and spices. Eur. J. Lipid Sci. Technol., 2006, 108, 776-793.
Sun, Z.G.; Chen, L.P.; Wang, F.W.; Xu, C.Y.; Geng, M. Protective effects of ginsenoside Rg1 against hydrogen peroxide-induced injury in human neuroblastoma cells. Neural Regen. Res., 2016, 11(7), 1159-1164.
[] [PMID: 27630703]
Malhotra, S.; Tavakkoli, M.; Edraki, N.; Miri, R.; Sharma, S.K.; Prasad, A.K.; Saso, L.; Len, C.; Parmar, V.S.; Firuzi, O. Neuroprotective and antioxidant activities of 4-methylcoumarins: development of structure-Activity relationships. Biol. Pharm. Bull., 2016, 39(9), 1544-1548.
[] [PMID: 27582333]
Achour, I.; Arel-Dubeau, A.M.; Renaud, J.; Legrand, M.; Attard, E.; Germain, M.; Martinoli, M.G. Oleuropein prevents neuronal death, mitigates mitochondrial superoxide production and modulates autophagy in a dopaminergic cellular model. Int. J. Mol. Sci., 2016, 17(8)E1293
[] [PMID: 27517912]
Ling, Y.Z.; Li, X.H.; Yu, L.; Zhang, Y.; Liang, Q.S.; Yang, X.D.; Wang, H.T. Protective effects of parecoxib on rat primary astrocytes from oxidative stress induced by hydrogen peroxide. J. Zhejiang Univ. Sci. B, 2016, 17(9), 692-702.
[] [PMID: 27604861]
Nousis, L.; Doulias, P.T.; Aligiannis, N.; Bazios, D.; Agalias, A.; Galaris, D.; Mitakou, S. DNA protecting and genotoxic effects of olive oil related components in cells exposed to hydrogen peroxide. Free Radic. Res., 2005, 39(7), 787-795.
[] [PMID: 16036359]
Vissers, M.N.; Zock, P.L.; Roodenburg, A.J.; Leenen, R.; Katan, M.B. Olive oil phenols are absorbed in humans. J. Nutr., 2002, 132(3), 409-417.
[] [PMID: 11880564]
Cumaoğlu, A.; Rackova, L.; Stefek, M.; Kartal, M.; Maechler, P.; Karasu, C. Effects of olive leaf polyphenols against H2O2 toxicity in insulin secreting β-cells. Acta Biochim. Pol., 2011, 58(1), 45-50.
[] [PMID: 21383995]
Andreyev, A.Y.; Kushnareva, Y.E.; Starkov, A.A. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc.), 2005, 70(2), 200-214.
[] [PMID: 15807660]
Porres-Martínez, M.; González-Burgos, E.; Carretero, M.E.; Gómez-Serranillos, M.P. Protective properties of Salvia lavandulifolia Vahl. essential oil against oxidative stress-induced neuronal injury. Food Chem. Toxicol., 2015, 80, 154-162.
[] [PMID: 25778348]
Kwon, S.H.; Hong, S.I.; Ma, S.X.; Lee, S.Y.; Jang, C.G. 3′,4′,7-Trihydroxyflavone prevents apoptotic cell death in neuronal cells from hydrogen peroxide-induced oxidative stress. Food Chem. Toxicol., 2015, 80, 41-51.
[] [PMID: 25720812]
Domitrović, R.; Jakovac, H.; Marchesi, V.V.; Šain, I.; Romić, Ž.; Rahelić, D. Preventive and therapeutic effects of oleuropein against carbon tetrachloride-induced liver damage in mice. Pharmacol. Res., 2012, 65(4), 451-464.
[] [PMID: 22214867]
Atakisi, O.; Erdogan, H.M.; Atakisi, E.; Citil, M.; Kanici, A.; Merhan, O.; Uzun, M. Effects of reduced glutathione on nitric oxide level, total antioxidant and oxidant capacity and adenosine deaminase activity. Eur. Rev. Med. Pharmacol. Sci., 2010, 14(1), 19-23.
[PMID: 20184085]
Butterfield, D.A.; Castegna, A.; Lauderback, C.M.; Drake, J. Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer’s disease brain contribute to neuronal death. Neurobiol. Aging, 2002, 23(5), 655-664.
[] [PMID: 12392766]
Beckman, J.S.; Koppenol, W.H. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am. J. Physiol., 1996, 271(5 Pt 1), C1424-C1437.
[] [PMID: 8944624]
Hu, J.; Luo, C.X.; Chu, W.H.; Shan, Y.A.; Qian, Z.M.; Zhu, G.; Yu, Y.B.; Feng, H. 20-Hydroxyecdysone protects against oxidative stress-induced neuronal injury by scavenging free radicals and modulating NF-κB and JNK pathways. PLoS One, 2012, 7(12)e50764
[] [PMID: 23239983]
Cai, J.; Li, J.; Liu, W.; Han, Y.; Wang, H. α2-adrenergic receptors in spiral ganglion neurons may mediate protective effects of brimonidine and yohimbine against glutamate and hydrogen peroxide toxicity. Neuroscience, 2013, 228, 23-35.
[] [PMID: 23069749]
Cabrerizo, S.; De La Cruz, J.P.; López-Villodres, J.A.; Muñoz-Marín, J.; Guerrero, A.; Reyes, J.J.; Labajos, M.T.; González-Correa, J.A. Role of the inhibition of oxidative stress and inflammatory mediators in the neuroprotective effects of hydroxytyrosol in rat brain slices subjected to hypoxia reoxygenation. J. Nutr. Biochem., 2013, 24(12), 2152-2157.
[] [PMID: 24231104]
Richard, N.; Arnold, S.; Hoeller, U.; Kilpert, C.; Wertz, K.; Schwager, J. Hydroxytyrosol is the major anti-inflammatory compound in aqueous olive extracts and impairs cytokine and chemokine production in macrophages. Planta Med., 2011, 77(17), 1890-1897.
[] [PMID: 21830187]

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