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Central Nervous System Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

Research Article

Anti-convulsant Action and Attenuation of Oxidative Stress by Citrus limon Peel Extracts in PTZ and MES Induced Convulsion in Albino Rats

Author(s): Dipika R. Sahu*, Bimalendu Chowdhury and Biswa M. Sahoo

Volume 20, Issue 3, 2020

Page: [177 - 185] Pages: 9

DOI: 10.2174/1871524920999200831153214

Price: $65

Abstract

Background: Citrus limon a small evergreen plant belongs to the family Rutaceae. These species are extensively cultivated throughout the world because of their multiple health benefits for humans and their applications in the pharmaceutical and food industries. Various studies were conducted using their plant parts (fruits, flowers, peels, leaves, blossoms) but the studies on peel extracts are very limited. However, the anticonvulsant activity of peels has not been studied yet.

Objective: The main goal of this study is to appraise the anticonvulsant effect stimulated by the antioxidant property of hydroalcoholic extracts of Citrus limon (HAECL) peels in various animal models.

Methods: The anticonvulsant and in vivo antioxidant activity of HAECL peels was observed by Maximal electric shock (MES) model, pentylenetetrazole (PTZ) induced clonic convulsion model and PTZ induced kindling test. The extract was administered to test groups at doses of 200, 400 and 600 mg/kg. orally in PTZ and MES methods. The highest dose of extract was given to the test grouped animals in case of a kindling test. After completion of the time period of kindling, the brains of all grouped animals were isolated and subjected to analyse oxidative stress parameters such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) biochemically to investigate the antioxidant profile of the plant.

Results: HAECL peels at doses of 400 and 600 mg/kg significantly (p<0.01) delayed the onset, decreased the duration of myoclonic spasm in PTZ induced seizure model and also significantly (p<0.01) decreased the duration of hind limb tonic extension (HLTE) as well as significantly (p<0.05) increased the postictal depression (PID) in MES model compared to control. In the PTZinduced kindling model, the malondialdehyde (MDA) level was elevated with a diminished level of SOD, CAT, GSH compared to the control group but pretreatment with HAECL at the highest dose reduced the MDA level and refined SOD, CAT and GSH status effectively.

Conclusion: From the above investigation, it was concluded that HAECL could produce significant anticonvulsant activity and also attenuate oxidative stress-induced during a seizure.

Keywords: Hydroalcoholic extracts, citrus limon peels, convulsion, pentylenetetrazole, albino rats, postictal depression.

Graphical Abstract
[1]
McNamara, J.O. Cellular and molecular basis of epilepsy. J. Neurosci., 1994, 14(6), 3413-3425.
[http://dx.doi.org/10.1523/JNEUROSCI.14-06-03413.1994] [PMID: 8207463]
[2]
Stafstrom, C.E. Epilepsy: A review of selected clinical syndromes and advances in basic science. J. Cereb. Blood Flow Metab., 2006, 26(8), 983-1004.
[http://dx.doi.org/10.1038/sj.jcbfm.9600265] [PMID: 16437061]
[3]
Meldrum, B.S. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J. Nutr., 2000, 130(4S)(Suppl.), 1007S-1015S.
[http://dx.doi.org/10.1093/jn/130.4.1007S] [PMID: 10736372]
[4]
Pivovarova, N.B.; Andrews, S.B. Calcium-dependent mitochondrial function and dysfunction in neurons. FEBS J., 2010, 277(18), 3622-3636.
[http://dx.doi.org/10.1111/j.1742-4658.2010.07754.x] [PMID: 20659161]
[5]
Rao, V.K.; Carlson, E.A.; Yan, S.S. Mitochondrial permeability transition pore is a potential drug target for neurodegeneration. Biochim. Biophys. Acta, 2014, 1842(8), 1267-1272.
[http://dx.doi.org/10.1016/j.bbadis.2013.09.003] [PMID: 24055979]
[6]
Bernardi, P.; Krauskopf, A.; Basso, E.; Petronilli, V.; Blachly-Dyson, E.; Di Lisa, F.; Forte, M.A. The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J., 2006, 273(10), 2077-2099.
[http://dx.doi.org/10.1111/j.1742-4658.2006.05213.x] [PMID: 16649987]
[7]
Gross, A.; McDonnell, J.M.; Korsmeyer, S.J. BCL-2 family members and the mitochondria in apoptosis. Genes Dev., 1999, 13(15), 1899-1911.
[http://dx.doi.org/10.1101/gad.13.15.1899] [PMID: 10444588]
[8]
Guo, Y.; Srinivasula, S.M.; Druilhe, A.; Fernandes-Alnemri, T.; Alnemri, E.S. Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. J. Biol. Chem., 2002, 277(16), 13430-13437.
[http://dx.doi.org/10.1074/jbc.M108029200] [PMID: 11832478]
[9]
Farnsworth, N.R.; Akerele, O.; Bingel, A.S.; Soejarto, D.D.; Guo, Z. Medicinal plants in therapy. Bull. World Health Organ., 1985, 63(6), 965-981.
[PMID: 3879679]
[10]
Al-Qudah, T.S.; Zahra, U.; Rehman, R.; Majeed, M.I.; Sadique, S.; Nisar, S.; Tahtamouni, R.W. Lemon: As a source of functional and medical ingredient. Int. J. Chem. Biochem. Sci., 2018, 14, 55-61.
[11]
Arias, B.A.; Ramón-Laca, L. Pharmacological properties of citrus and their ancient and medieval uses in the Mediterranean region. J. Ethnopharmacol., 2005, 97(1), 89-95.
[http://dx.doi.org/10.1016/j.jep.2004.10.019] [PMID: 15652281]
[12]
Del Rio, J.A.; Fuster, M.D.; Gomez, P.; Porras, I.; Garcia Lidn, A.; Ortuo, A. Citrus limon: A source of flavonoids of pharmaceutical interest. Food Chem., 2004, 84(3), 457-461.
[http://dx.doi.org/10.1016/S0308-8146(03)00272-3]
[13]
Costa Marques, T.H.; Santos De Melo, C.H.; Fonseca De Carvalho, R.B.; Costa, L.M.; De Souza, A.A.; David, J.M.; De Lima David, J.P.; De Freitas, R.M. Phytochemical profile and qualification of biological activity of an isolated fraction of Bellis perennis. Biol. Res., 2013, 46(3), 231-238.
[http://dx.doi.org/10.4067/S0716-97602013000300002] [PMID: 24346069]
[14]
Ali, J.; Das, B.; Saikia, T. Antimicrobial activity of lemon peel (citrus limon) extract Int. J. of Curr. Phar. Res., 2017.
[15]
Khan, R.A.; Riaz, A. Behavioral effects of Citrus limon in rats. Metab. Brain Dis., 2015, 30(2), 589-596.
[http://dx.doi.org/10.1007/s11011-014-9616-2] [PMID: 25227172]
[16]
Azman, N.F.I.N.; Azlan, A.; Khoo, H.E.; Razman, M.R. Antioxidant properties of fresh and frozen peels of citrus species. Curr. Res. Nutr. Food Sci., 2019, 7(2), 331-339.
[http://dx.doi.org/10.12944/CRNFSJ.7.2.03]
[17]
Makni, M.; Jemai, R.; Kriaa, W.; Chtourou, Y.; Fetoui, H. Citrus limon from Tunisia: phytochemical and physicochemical properties and biological activities. BioMed Res. Int., 2018, 20186251546
[http://dx.doi.org/10.1155/2018/6251546] [PMID: 29568760]
[18]
Hegazy, A.E.; Ibrahium, M.I. Antioxidant Activities of Orange Peel Extracts. World Appl. Sci. J., 2012, 18(5), 684-688.
[19]
Bhandary, S.K.; Kumari, S.; Bhat, V.S.; Sharmila, K.P.; Bekal, M.P. Preliminary phytochemical screening of various extracts of Punica granatum peel, whole fruit and seeds. Nitte University J. Health Sci, 2012, 2, 34-38.
[20]
Madaan, R.; Bansal, G.; Kumar, S.; Sharma, A. Estimation of total phenolic and flavonoids in extracts of Actaea spicata roots and antioxidant activity studies. Indian J. Pharm. Sci., 2011, 73(6), 666-669.
[http://dx.doi.org/10.4103/0250-474X.100242] [PMID: 23112402]
[21]
Maithili, V.; Dhanabal, S.P.; Mahendran, S.; Vadivelan, R. Antidiabetic activity of ethanolic extract of tubers of Dioscorea alata in alloxan induced diabetic rats. Indian J. Pharmacol., 2011, 43(4), 455-459.
[http://dx.doi.org/10.4103/0253-7613.83121] [PMID: 21845005]
[22]
Suresh babu, A.R.; Karkib, S.S. Anticonvulsant activity of various extracts of leaves of calotropis gigantean linn against seizure induced models. Int. J. Pharm. Pharm. Sci., 2011, 3, 200-203.
[23]
Gupta, R.; Sharma, K.K.; Afzal, M.; Damanhouri, Z.A.; Ali, B.; Kaur, R.; Kazmi, I.; Anwar, F. Anticonvulsant activity of ethanol extracts of Vetiveria zizanioides roots in experimental mice. Pharm. Biol., 2013, 51(12), 1521-1524.
[http://dx.doi.org/10.3109/13880209.2013.799710] [PMID: 23863081]
[24]
Tambe, R.; Jain, P.; Patil, S.; Ghumatkar, P.; Sathaye, S. Protective Effects of Diosgenin in Pentylenetetrazole Induced Kindling Model of Epilepsy in Mice. Neurochem. Neuropharmacol., 2015, 1(1), 2469-2497.
[http://dx.doi.org/10.4172/2469-9780.1000106]
[25]
Gaur, V.; Aggarwal, A.; Kumar, A. Possible nitric oxide mechanism in the protective effect of hesperidin against ischemic reperfusion cerebral injury in rats. Indian J. Exp. Biol., 2011, 49(8), 609-618.
[PMID: 21870429]
[26]
Pasha, K.V.; Sadasivudu, B. Intracellular content of thiol compounds, thiobarbituric acid reactive substances and gamma-glutamyl transpeptidase in rat brain during anoxia. Neurosci. Lett., 1984, 46(2), 209-214.
[http://dx.doi.org/10.1016/0304-3940(84)90443-9] [PMID: 6146121]
[27]
Frantseva, M.V.; Perez Velazquez, J.L.; Tsoraklidis, G.; Mendonca, A.J.; Adamchik, Y.; Mills, L.R.; Carlen, P.L.; Burnham, M.W. Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience, 2000, 97(3), 431-435.
[http://dx.doi.org/10.1016/S0306-4522(00)00041-5] [PMID: 10828526]
[28]
Gupta, Y.K.; Veerendra Kumar, M.H.; Srivastava, A.K. Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. Pharmacol. Biochem. Behav., 2003, 74(3), 579-585.
[http://dx.doi.org/10.1016/S0091-3057(02)01044-4] [PMID: 12543222]
[29]
Pajovic, S.S.; Radojcic, M.B.; Borojevic, N.D.; Radosevic, J.L.M. Role of Superoxide Dismutase: In Industrialization of Breast Cancer Radiation Therapy Protocols. Arch. Oncol., 2003, 11(3), 191-192.
[http://dx.doi.org/10.2298/AOO0303191P]
[30]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[PMID: 14907713]
[31]
Sohi, S.; Shri, R. Neuropharmacological potential of the genus Citrus: A review. J. Of Pharmacog. Phytochem., 2018, 7(2), 1538-1548.
[32]
Subramaniam, S.; Rho, J.M.; Penix, L.; Donevan, S.D.; Fielding, R.P.; Rogawski, M.A. Felbamate block of the N-methyl-D-aspartate receptor. J. Pharmacol. Exp. Ther., 1995, 273(2), 878-886.
[PMID: 7752093]
[33]
McNamara, J.O. Pharmacotherapy of the epilepsies In Goodman and Gilman’sThe Pharmacol. Basis of Therap. 9th Edi, New York., 2006, pp. 461-486.
[34]
Tandon, V.R.; Gupta, R.K. An experimental evaluation of anticonvulsant activity of Vitex-negundo. Indian J. Physiol. Pharmacol., 2005, 49(2), 199-205.
[PMID: 16170989]
[35]
Hosseini, M.; Pkan, P.; Rakhshandeh, H.; Aghaie, A.; Sadeghnia, H.R.; Rahbardar, G. The effect of hydro-alcoholic extract of citrus flower on pentylenetetrazole and maximum electrical induced seizures in mice. World Appl. Sci. J., 2011, 15(08), 1104-1109.
[36]
Campelo, L.M.L.; Lima, S.G.D.; Feitosa, C.M.; Freitos, R.M.D. Evaluation of central nervous system effects of Citrus limon essential oil in mice. Rev. Bras. Farmacogn. Braz. J. Pharmacogn., 2011, 21(04), 668-673.
[http://dx.doi.org/10.1590/S0102-695X2011005000086]
[37]
De Sarro, A.; Cecchetti, V.; Fravolini, V.; Naccari, F.; Tabarrini, O.; De Sarro, G. Effects of novel 6-desfluoroquinolones and classic quinolones on pentylenetetrazole-induced seizures in mice. Antimicrob. Agents Chemother., 1999, 43(7), 1729-1736.
[http://dx.doi.org/10.1128/AAC.43.7.1729] [PMID: 10390231]
[38]
Rajnarayan, K.; Reddy, S.M.; Chailuvadi, M.R.; Krishna, D.R. Bioflavanoids classification: Pharmacological, biochemical effect and therapeutic potential. Indian J. Pharmacol., 2001, 33(1), 2-16.
[39]
Prokopenko, Y.; Tsyvunin, V.; Shtrygol’, S.; Georgiyants, V. In vivo anticonvulsant activity of extracts and protopine from the fumaria schleicheri herb. Sci. Pharm., 2015, 84(3), 547-554.
[http://dx.doi.org/10.3390/scipharm84030547] [PMID: 28117320]
[40]
Choudhary, N.; Bijjem, K.R.V.; Kalia, A.N. Antiepileptic potential of flavonoids fraction from the leaves of Anisomeles malabarica. J. Ethnopharmacol., 2011, 135(2), 238-242.
[http://dx.doi.org/10.1016/j.jep.2011.02.019] [PMID: 21354295]
[41]
Azanchi, T.; Shafaroodi, H.; Asgarpanah, J. Anticonvulsant activity of Citrus aurantium blossom essential oil (neroli): involvment of the GABAergic system. Nat. Prod. Commun., 2014, 9(11), 1615-1618.
[PMID: 25532295]
[42]
Thakuria, N.; Das, S.; Bewan, B. Anticonvulsant activity of Citrus maximus leaves in experimental animal models. Asian J. Pharma. And Clinical Res., 2016, 9, 1-3.
[http://dx.doi.org/10.22159/ajpcr.2016.v9s3.14576]
[43]
Nagula, J.B.; Reddy, N.L. Evaluation of antiepileptic property of Citrus sinensis (leaf extract) by pentylenetetrazole (PTZ) induced convulsions in mice. Sch. J. App. Med. Sci., 2017, 5(7E), 2830-2835.
[44]
Kulkarni, S.K.; George, B. Pentylenetetrazol-induced kindling in animals: protective effect of BR-16A. Indian J. Exp. Biol., 1995, 33(6), 424-427.
[PMID: 7590948]
[45]
Rauca, C.; Zerbe, R.; Jantze, H. Formation of free hydroxyl radicals after pentylenetetrazol-induced seizure and kindling. Brain Res., 1999, 847(2), 347-351.
[http://dx.doi.org/10.1016/S0006-8993(99)02084-3] [PMID: 10575107]
[46]
Costa, L.G. Cell signaling and neurotoxic events Principles of Neurotoxicol, 1994.
[47]
Weydert, C.J.; Cullen, J.J. Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat. Protoc., 2010, 5(1), 51-66.
[http://dx.doi.org/10.1038/nprot.2009.197] [PMID: 20057381]
[48]
Dringen, R.; Gutterer, J.M.; Hirrlinger, J. Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur. J. Biochem., 2000, 267(16), 4912-4916.
[http://dx.doi.org/10.1046/j.1432-1327.2000.01597.x] [PMID: 10931173]

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