Original Article

Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson's Disease

Abstract

Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD). We examined the effects of ellagic acid (EA) on locomotion, pallidal local EEG, and its frequency bands' power and also cerebral antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). 6-OHDA (16 µg/2µ l) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection. EA (50 mg/kg/2 ml, by gavages) was administered in PD+EA group. One group of MFB-lesioned rats received pramipexole (PPX; 2 mg/kg/2 ml, by gavages) as a positive control group (PD+PPX group). Motor activity was assessed by stride length, rotarod, and cylinder tests. Pallidal local EEG was recorded in freely moving rats. The levels of malondialdehyde (MDA) besides Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured in both striatum and hippocampus tissues. MFB lesion caused significant reduction of stride-length (P<0.001), bar decent latency (P<0.001) and frequency bands' power of pallidal EEG (P<0.001). Use of 6-OHDA caused a reduction in the GPx (P<0.001) and SOD (P<0.001) activities while increased significantly the levels of MDA (P<0.001) in MFB-lesioned rats. EA significantly restored all above parameters. The results show that EA can improve the motor impairments and electrophysiological performance in the MFB-lesioned rats via raising the cerebral antioxidant contents. Therefore, EA can protect the brain against free radicals-induced neural damage and may be beneficial in the treatment of PD.

Philippens IH, t Hart BA, Torres G. The MPTP marmoset model of parkinsonism: a multi-purpose non-human primate model for neurodegenerative diseases. Drug Discov Today 2010;15:985-90 .

Moreira EL, Rial D, Aguiar AS, Jr., Figueiredo CP, Siqueira JM, DalBo S, et al. Proanthocyanidin-rich fraction from Croton celtidifolius Baill confers neuroprotection in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rat model of Parkinson's disease. J Neural Transm 2010;117:1337-51 .

Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging

;23:719-35.

Chaturvedi RK, Shukla S, Seth K, Chauhan S, Sinha C, Shukla Y, et al. Neuroprotective and neurorescue effect of black tea extract in 6-hydroxydopamine-lesioned rat model of Parkinson's disease. Neurobiol Dis

;22:421-34.

Magnin M, Morel A, Jeanmonod D. Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients. Neuroscience 2000; 96:549-64 .

Kuoppamaki M, Rothwell JC, Brown RG, Quinn N, Bhatia KP, Jahanshahi M. Parkinsonism following bilateral lesions of the globus pallidus: performance on a variety of motor tasks shows similarities with Parkinson's disease. J Neurol Neurosurg Psychiatry 2005;76:482-90.

Sarkaki A, Eidypour Z, Motamedi F, keramati K, Farbood Y. Motor disturbances and thalamic electrical power of frequency bands' improve by grape seed extract in animal model of Parkinson's disease. Avicenna J Phytomed 2012;2:222-32.

Engel AK, Fries P, Singer W. Dynamic predictions: oscillations and synchrony in top-down processing. Nat Rev Neurosci 2001;2:704-16.

Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, Rodriguez M, et al. Missing pieces in the Parkinson's disease puzzle. Nat Med 2010;16:653-61.

Hwang DS, Kim HG, Kwon HJ, Cho JH, Lee CH, Lee JM, et al. Dangguijakyak-san, a medicinal herbal formula,protects dopaminergic neurons from 6-hydroxydopamine- induced neurotoxicity. J Ethnopharmacol 2011;133:934-9.

Hassanzadeh P, Arbabi E, Rostami F. The ameliorative effects of sesamol against seizures, cognitive impairment and oxidative stress in the experimental model of epilepsy. Iran J Basic Med Sci 2014;17:100-7.

Dolatshahi M, Farbood Y, Sarkaki A, Taqhi SM. Ellagic acid improves hyperalgesia and cognitive deficiency in 6- hydroxidopamine induced rat model of Parkinson’s disease. Iran J Basic Med Sci 2015;18:38-46.

Braidy N, Selvaraju S, Essa MM, Vaishnav R, Al-Adawi S, Al-Asmi A, et al. Neuroprotective effects of a variety of pomegranate juice extracts against MPTP-induced cytotoxicity and oxidative stress in human primary neurons. Oxid Med Cell Longev 2013:685909.

Wada L, Ou B. Antioxidant activity and phenolic content of Oregon caneberries. J Agric Food Chem 2002;50:3495-500.

Whitley AC, Stoner GD, Darby MV, Walle T. Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid-extensive binding to protein and DNA. Biochem Pharmacol 2003;66:907-15.

Lei F, Xing DM, Xiang L, Zhao YN, Wang W, Zhang LJ, et al. Pharmacokinetic study of ellagic acid in rat after oral administration of pomegranate leaf extract. J Chromatogr B Analyt Technol Biomed Life Sci

;796:189-94.

Uzar E, Fırat U, Altun Y, Alp H, Evliyaoglu O, Cevik MU. Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats. Neurological Sci 2012;33:567-74.

Tadaiesky MT, Dombrowski PA, Figueiredo CP, Cargnin-Ferreira E, Da Cunha C, Takahashi RN. Emotional, cognitive and neurochemical alterations in a premotor stage model of Parkinson's disease. Neuroscience 2008;156:830-40.

Paxinos G, Watson C. The rat brain stereotaxic coordinates. (Accessed in May 12, 2016, at http://www.callisto-science.org/NSI/Neuroscience_Image _Database/PDFFILES/RBSC_INT.PDF).

Sarkaki A, Norooz Zare F, Farbood Y, Pileverian AA.Impaired movements in 6-OHDA induced Parkinson’s rat model improves by pomegranate seed hydroalcoholic extract. HealthMed 2013b;7:348-58.

Rizelio V, Szawka RE, Xavier LL, Achaval M, Rigon P, Saur L, et al. Lesion of the subthalamic nucleus reverses motor deficits but not death of nigrostriatal dopaminergic neurons in a rat 6-hydroxydopamine-lesion model of Parkinson's disease. Braz J Med Biol Res 2010;43:85-95.

Metz GA, Tse A, Ballermann M, Smith LK, Fouad K.The unilateral 6-OHDA rat model of Parkinson's disease revisited: an electromyographic and behavioural analysis. Eur J Neurosci 2005;22:735-44.

Sameri MJ, Sarkaki AR, Farbood Y, Mansouri MT.Motor disorders and impaired electrical power of pallidal EEG improved by gallic acid in animal model of parkinson's disease. Pak J Biol Sci 2011;14:1109-16.

Sarkaki A, Badavi M, Hoseiny N, Gharibnaseri MK, Rahim F. Postmenopausal effects of intrastriatal estrogen on catalepsy and pallidal electroencephalogram in an animal model of Parkinson's disease. Neuroscience 2008;154:940-5.

Mansouri MT, Farbood Y, Sameri MJ, Sarkaki A, Naghizadeh B, Rafeirad M. Neuroprotective effects of oral gallic acid against oxidative stress induced by 6- hydroxydopamine in rats. Food Chem 2013;138:1028-33.

Kelly E, Jenner P, Marsden CD. Behavioural effects mediated by unilateral nigral dopamine receptor stimulation in the rat. Exp Brain Res 1984;55:243-52.

Singh A, Levin J, Mehrkens JH, Kai B. Alpha frequency modulation in the human basal ganglia is dependent on motor task. Eur J Neurosci 2011; 33:960-7.

Kempf F, Brucke C, Salih F, Trottenberg T, Kupsch A, Schneider GH, et al. Gamma activity and reactivity in human thalamic local field potentials. Eur J Neurosci 2009;29:943-53.

Brown P. Abnormal oscillatory synchronisation in the motor system leads to impaired movement. Curr Opin Neurobiol 2007;17:656-64.

Jenkinson N, Brown P. New insights into the relationship between dopamine, beta oscillations and motor function. Trends Neurosci 2011;34:611-8.

Brown P, Williams D. Basal ganglia local field potential activity: character and functional significance in the human. Clin Neurophysiol 2005;116:2510-9.

Brown P. Oscillatory nature of human basal ganglia activity: relationship to the pathophysiology of Parkinson's disease. Mov Disord 2003;18:357-63.

Parr-Brownlie LC, Hyland BI. Bradykinesia induced by dopamine D2 receptor blockade is associated with reduced motor cortex activity in the rat. J Neurosci 2005;25:5700-9.

Hritcu L, Ciobica A, Artenie V. Effects of right-unilateral 6-hydroxydopamine infusion-induced memory impairment and oxidative stress: relevance for Parkinson’s disease. Central Eur J Biol 2008;3:250-7.

Fahn S, Sulzer D. Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx 2004;1:139-54.

Dauer W, Przedborski S. Parkinson's disease:mechanisms and models. Neuron 2003;39:889-909.

Huang Z, de la Fuente-Fernandez R, Stoessl AJ. Etiology of Parkinson's disease. Can J Neurol Sci 2003;30:S10-8.

Miguel G, Dandlen S, Antunes D, Neves A, Martins D.The Effect of Two Methods of Pomegranate (Punica granatum L) Juice Extraction on Quality During Storage at $4^circ$ C. J Biomed Biotechnol 2004;2004:332-7.

Tamaddonfard E, Farshid AA, Asri-Rezaee S, Javadi S, Khosravi V, Rahman B, et al. Crocin improved learning and memory impairments in streptozotocin-induced diabetic rats. Iran J Basic Med Sci 2013;16:91-100.

Chis IC, Ungureanu MI, Marton A, Simedrea R, Muresan A, Postescu ID, et al. Antioxidant effects of a grape seed extract in a rat model of diabetes mellitus. Diab Vasc Dis Res 2009;6:200-4.

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IssueVol 54, No 8 (2016) QRcode
SectionOriginal Article(s)
Keywords
Parkinson's disease Ellagic acid Locomotion EEG Antioxidants

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How to Cite
1.
Sarkaki A, Farbood Y, Dolatshahi M, Mansouri SMT, Khodadadi A. Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson’s Disease. Acta Med Iran. 2016;54(8):494-502.