The potential neuroprotective roles of olive leaf extract in an epilepsy rat model induced by kainic acid

Safoura Khamse , Saeed Mohammadian Haftcheshmeh, Seyed Shahabeddin Sadr , Mehrdad Roghani, Mohammad Kamalinejad, Parvane Mohseni Moghaddam, Ravieh Golchoobian, Fatemeh Ebrahimi

Abstract


Background and purpose: Epilepsy is recognized as a chronic neurologic disease. Increasing evidence has addressed the antioxidant and anti-inflammatory roles of olive leaf extract (OLE) in neurodegenerative diseases. So, the current study aimed to investigate the neuroprotective roles of OLE in epilepsy.

Experimental approach: Forty rats were divided into 4 groups including a control group, sham group, kainic acid (KA) group, and KA + OLE group. KA (4 μg/rat) was injected intrahippocampal, and OLE (300 mg/kg) was orally administrated for 4 weeks. Animals were sacrificed, and their hippocampi were isolated. KA-induced seizure activity was recorded. Oxidative stress index was assessed by measuring its indicators including malondialdehyde (MDA), nitrite, nitrate, and glutathione (GSH) as well as the catalase (CAT) activity. The supernatant concentration of tumor necrosis factor-α (TNF-α) and the apoptosis rate in neurons were measured.

Findings/Results: Treatment with OLE significantly reduced the seizure score. OLE decreased oxidative stress index by reducing the concentration of MDA, nitrite, and nitrate as well as increasing the level of GSH. OLE had a significant anti-apoptotic effect on neurons. However, CAT activity and the level of TNF-α were not affected.

Conclusion and implications: Our findings indicated neuroprotective properties of OLE, which is mainly mediated by its antioxidant and anti-apoptotic effects, therefore, could be considered as a valuable therapeutic supplement for epilepsy.

 

 


Keywords


Epilepsy; Inflammation; Kainic acid; Olive leaf extract; Oxidative stress.

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Duncan JS, Sander JW, Sisodiya SM, Walker MC. Adult epilepsy. Lancet. 2006;367(9516):1087-1100.

DOI: 10.1016/S0140-6736(06)68477-8.

Harden CL. The co-morbidity of depression and epilepsy: epidemiology, etiology, and treatment. Neurology. 2002;59(6 Suppl 4):S48-S55.

DOI: 10.1212/wnl.59.6_suppl_4.s48.

De Boer HM. Out of the shadows: a global campaign against epilepsy. Epilepsia. 2002;43(Supple 6):7-8.

DOI: 10.1046/j.1528-1157.43.s.6.4.x.

Perucca E, French J, Bialer M. Development of new antiepileptic drugs: challenges, incentives, and recent advances. Lancet Neurol. 2007;6(9):793-804.

DOI: 10.1016/S1474-4422(07)70215-6.

Noor NA, Mohammed HS, Khadrawy YA, Ezz HSA, Radwan NM. Evaluation of the neuroprotective effect of taurine and green tea extract against oxidative stress induced by pilocarpine during status epilepticus. J Basic Appl Zool. 2015;72:8-15.

DOI: 10.1016/j.jobaz.2015.02.001.

Pitkänen A, Lukasiuk K. Molecular and cellular basis of epileptogenesis in symptomatic epilepsy. Epilepsy Behav. 2009;14( Suppl 1):16-25.

DOI: 10.1016/j.yebeh.2008.09.023.

Lorigados Pedre L, Morales Chacon LM, Orozco Suarez S, Pavon Fuentes N, Estupinan Diaz B, Serrano Sanchez T, et al. Inflammatory mediators in epilepsy. Curr Pharm Des. 2013;19(38):6766-6772.

DOI: 10.2174/1381612811319380009.

Vezzani A, Granata T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia. 2005;46(11):1724-1743.

DOI: 10.1111/j.1528-1167.2005.00298.x.

McGeer PL, McGeer EG. Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism Relat Disord. 2004;10(Suppl 1):S3-S7.

DOI: 10.1016/j.parkreldis.2004.01.005.

Riikonen R. Infantile spasms: therapy and outcome. J Child Neurol. 2004;19(6):401-404.

DOI: 10.1177/088307380401900601.

Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol. 2011;7(1):31-40.

DOI: 10.1038/nrneurol.2010.178.

Vezzani A, Lang B, Aronica E. Immunity and inflammation in epilepsy. Cold Spring Harb Perspect Med. 2015;6(2):a022699,1-21.

DOI: 10.1101/cshperspect.a022699.

Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49(11):1603-1616.

DOI: 10.1016/j.freeradbiomed.2010.09.006.

Khamse S, Sadr SS, Roghani M, Hasanzadeh G, Mohammadian M. Rosmarinic acid exerts a neuroprotective effect in the kainate rat model of temporal lobe epilepsy: underlying mechanisms. Pharm Biol. 2015;53(12):1818-1825.

DOI: 10.3109/13880209.2015.1010738.

Barnham KJ, Masters CL, Bush AI. Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov. 2004;3(3):205-214.

DOI: 10.1038/nrd1330.

Momtazi-Borojeni AA, Haftcheshmeh SM, Esmaeili SA, Johnston TP, Abdollahi E, Sahebkar A. Curcumin: a natural modulator of immune cells in systemic lupus erythematosus. Autoimmun Rev. 2018;17(2):125-135.

DOI: 10.1016/j.autrev.2017.11.016.

Kahkhaie KR, Mirhosseini A, Aliabadi A, Mohammadi A, Mousavi MJ, Haftcheshmeh SM, et al. Curcumin: a modulator of inflammatory signaling pathways in the immune system. Inflammopharmacology.2019;27(5):885-900.

DOI: 10.1007/s10787-019-00607-3.

El SN, Karakaya S. Olive tree (Olea europaea) leaves: potential beneficial effects on human health. Nutr Rev. 2009;67(11):632-638.

DOI: 10.1111/j.1753-4887.2009.00248.x.

Gorzynik-Debicka M, Przychodzen P, Cappello F, Kuban-Jankowska A, Marino Gammazza AM, Knap N, et al. Potential health benefits of olive oil and plant polyphenols. Int J Mol Sci. 2018;19(3):686-698.

DOI: 10.3390/ijms19030686.

Fito M, de la Torre R, Covas MI. Olive oil and oxidative stress. Mol Nutr Food Res. 2007;51(10):1215-1224.

DOI: 10.1002/mnfr.200600308.

Martin-Pelaez S, Covas MI, Fito M, Kusar A, Pravst I. Health effects of olive oil polyphenols: recent advances and possibilities for the use of health claims. Mol Nutr Food Res. 2013;57(5):760-771.

DOI: 10.1002/mnfr.201200421.

Yu H, Liu P, Tang H, Jing J, Lv X, Chen L, et al. Oleuropein, a natural extract from plants, offers neuroprotection in focal cerebral ischemia/reperfusion injury in mice. Eur J Pharmacol. 2016;775:113-119.

DOI: 10.1016/j.ejphar.2016.02.027.

Dekanski D, Selakovic V, Piperski V, Radulovic Z, Korenic A, Radenovic L. Protective effect of olive leaf extract on hippocampal injury induced by transient global cerebral ischemia and reperfusion in Mongolian gerbils. Phytomedicine. 2011;18(13):1137-1143.

DOI: 10.1016/j.phymed.2011.05.010.

Khalatbary AR, Ahmadvand H. Neuroprotective effect of oleuropein following spinal cord injury in rats. Neurol Res. 2012;34(1):44-51.

DOI: 10.1179/1743132811Y.0000000058.

Sarbishegi M, Charkhat Gorgich EA, Khajavi O, Komeili G, Salimi S. The neuroprotective effects of hydro-alcoholic extract of olive (Olea europaea L.) leaf on rotenone-induced Parkinson's disease in rat. Metab Brain Dis. 2018;33(1):79-88.

DOI: 10.1007/s11011-017-0131-0.

Singleton VL, Orthofer R, Lamuela-Raventós R. Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. Meth Enz. 1999;299:152-178.

DOI.org/10.1016/S0076-6879(99)99017-1

Lin JY, Tang CY. Determination of total phenolic and flavonoid contents in selected fruits and vegetables, as well as their stimulatory effects on mouse splenocyte proliferation. Food Chem. 2007;101(1):140-147.

DOI: 10.1016/j.foodchem.2006.01.014.

Khamse S, Sadr SS, Roghani M, Rashvand M, Mohammadian M, Marefati N, et al. The effect of rosmarinic acid on apoptosis and nNOS immunoreactivity following intrahippocampal kainic acid injections in rats. Basic Clin Neurosci. 2020;11(1):41-48.

DOI: 10.32598/bcn.9.10.340.

Mohseni Moghaddam P, Sadr SS, Roghani M, Arabzadeh S, Khamse S, Zamani E, et al. Huperzine A ameliorates cognitive dysfunction and neuroinflammation in kainic acid induced epileptic rats by antioxidant activity and NLRP 3/caspase1 pathway inhibition. Clin Exp Pharmacol Physiol. 2019;46(4):360-372.

DOI: 10.1111/1440-1681.13064.

Ebrahimi F, Sadr SS, Roghani M, Khamse S, Mohammadian Haftcheshmeh S, Navid Hamidi M, et al. Assessment of the protective effect of KN‐93 drug in systemic epilepsy disorders induced by pilocarpine in male rat. J Cell Biochem. 2019;120(9):15906-15914.

DOI: 10.1002/jcb.28864.

Baluchnejadmojarad T, Roghani M. Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress. Behav Brain Res. 2011;224(2):305-310.

DOI: 10.1016/j.bbr.2011.06.007.

Sedaghat R, Taab Y, Kiasalari Z, Afshin-Majd S, Baluchnejadmojarad T, Roghani M. Berberine ameliorates intrahippocampal kainate-induced status epilepticus and consequent epileptogenic process in the rat: underlying mechanisms. Biomed Pharmacother. 2017;87:200-208.

DOI: 10.1016/j.biopha.2016.12.109.

Tchekalarova J, Petkova Z, Pechlivanova D, Moyanova S, Kortenska L, Mitreva R, et al. Prophylactic treatment with melatonin after status epilepticus: effects on epileptogenesis, neuronal damage, and behavioral changes in a kainate model of temporal lobe epilepsy. Epilepsy Behav. 2013;27(1):174-187.

DOI: 10.1016/j.yebeh.2013.01.009.

Kanada A, Nishimura Y, Yamaguchi JY, Kobayashi M, Mishima K, Horimoto K, et al. Extract of Ginkgo biloba leaves attenuates kainate-induced increase in intracellular Ca2+ concentration of rat cerebellar granule neurons. Biol Pharm Bull. 2005;28(5):934-936.

DOI: 10.1248/bpb.28.934.

Amatniek JC, Hauser WA, DelCastillo-Castaneda C, Jacobs DM, Marder K, Bell K, et al. Incidence and predictors of seizures in patients with Alzheimer's disease. Epilepsia. 2006;47(5):867-872.

DOI: 10.1111/j.1528-1167.2006.00554.x.

Arundine M, Tymianski M. Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium. 2003;34(4-5):325-337.

DOI: 10.1016/s0143-4160(03)00141-6.

Aguiar CC, Almeida AB, Araujo PV, de Abreu RN, Chaves EM, do Vale OC, et al. Oxidative stress and epilepsy: literature review. Oxid Med Cell Longev. 2012;2012:795259.

DOI: 10.1155/2012/795259.

Butterfield DA, Drake J, Pocernich C, Castegna A. Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid β-peptide. Trends Mol Med. 2001;7(12):548-554.

DOI: 10.1016/s1471-4914(01)02173-6.

Liang LP, Patel M. Seizure-induced changes in mitochondrial redox status. Free Radic Biol Med. 2006;40(2):316-322.

DOI: 10.1016/j.freeradbiomed.2005.08.026.

Cock HR. The role of mitochondria and oxidative stress in neuronal damage after brief and prolonged seizures. Prog Brain Res. 2002;135:187-196.

DOI: 10.1016/S0079-6123(02)35018-0.

Patel M. Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures. Free Radic Biol Med. 2004;37(12):1951-1962.

DOI: 10.1016/j.freeradbiomed.2004.08.021.

Gluck MR, Jayatilleke E, Shaw S, Rowan AJ, Haroutunian V. CNS oxidative stress associated with the kainic acid rodent model of experimental epilepsy. Epilepsy Res. 2000;39(1):63-71.

DOI: 10.1016/s0920-1211(99)00111-4.

Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016;1863(12):2977-2992.

DOI: 10.1016/j.bbamcr.2016.09.012.

Hsieh PF, Hou CW, Yao PW, Wu SP, Peng YF, Shen ML, et al. Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation. J Neuroinflammation. 2011;8:57-66.

DOI: 10.1186/1742-2094-8-57.

Liang LP, Ho YS, Patel M. Mitochondrial superoxide production in kainate-induced hippocampal damage. Neuroscience. 2000;101(3):563-570.

DOI: 10.1016/s0306-4522(00)00397-3.

Pourkhodadad S, Alirezaei M, Moghaddasi M, Ahmadvand H, Karami M, Delfan B, et al. Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats. J Physiol Sci. 2016;66(5):397-405.

DOI: 10.1007/s12576-016-0437-4.

Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol. 2000;1(2):120-129.

DOI: 10.1038/35040009

Chuang YC, Chen SD, Lin TK, Liou CW, Chang WN, Chan SHH, et al. Upregulation of nitric oxide synthase II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following induction of experimental temporal lobe status epilepticus in the rat. Neuropharmacology. 2007;52(5):1263-1273.

DOI: 10.1016/j.neuropharm.2007.01.010.

Montecot C, Rondi-Reig L, Springhetti V, Seylaz J, Pinard E. Inhibition of neuronal (type 1) nitric oxide synthase prevents hyperaemia and hippocampal lesions resulting from kainate-induced seizures. Neuroscience. 1998;84(3):791-800

DOI: 10.1016/s0306-4522(97)00566-6.

Pasban-Aliabadi H, Esmaeili-Mahani S, Sheibani V, Abbasnejad M, Mehdizadeh A, Yaghoobi MM. Inhibition of 6-hydroxydopamine-induced PC12 cell apoptosis by olive (Olea europaea L.) leaf extract is performed by its main component oleuropein. Rejuvenation Res. 2013;16(2):134-142.

DOI: 10.1089/rej.2012.1384.

Achour I, Arel-Dubeau AM, Renaud J, Legrand M, Attard E, Germain M, et al. Oleuropein prevents neuronal death, mitigates mitochondrial superoxide production and modulates autophagy in a dopaminergic cellular model. Int J Mol Sci. 2016;17(8):1293-1309.

DOI: 10.3390/ijms17081293.

Sarbishegi M, Mehraein F, Soleimani M. Antioxidant role of oleuropein on midbrain and dopaminergic neurons of substantia nigra in aged rats. Iran Biomed J. 2014;18(1):16-22.

DOI: 10.6091/ibj.1274.2013.

Yu G, Deng A, Tang W, Ma J, Yuan C, Ma J. Hydroxytyrosol induces phase II detoxifying enzyme expression and effectively protects dopaminergic cells against dopamine- and 6-hydroxydopamine induced cytotoxicity. Neurochem Int. 2016;96:113-120.

DOI: 10.1016/j.neuint.2016.03.005.

Zafar KS, Inayat-Hussain SH, Siegel D, Bao A, Shieh B, Ross D. Overexpression of NQO1 protects human SK-N-MC neuroblastoma cells against dopamine-induced cell death. Toxicol Lett. 2006;166(3):261-267.

DOI: 10.1016/j.toxlet.2006.07.340.

Wang L, Geng C, Jiang L, Gong D, Liu D, Yoshimura H, et al. The anti-atherosclerotic effect of olive leaf extract is related to suppressed inflammatory response in rabbits with experimental atherosclerosis. Eur J Nutr. 2008;47(5):235-243.

DOI: 10.1007/s00394-008-0717-8.


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