PHYTOFLAVONOIDS: ANTIEPILEPTICS FOR THE FUTURE
Keywords:
Flavonoids, Epilepsy, Epilepsy-induced comorbidities, Flavonoidal plantsAbstract
Epilepsy has become second most common neurological disorder affecting 70 million people worldwide. Several shortcomings appeared with the use of conventional antiepileptic drugs (AEDs) like, inadequate seizure control, side effects, cost, potentiation of epilepsy-induced co-morbidities, etc., which limit their use as comprehensive therapy. Phytoflavonoids in this regard have been observed to be promising AEDs which can interact with most of the possible targets involved in the pathogenesis of epilepsy. They show  modulatory effect on voltage gated sodium channels, calcium channels, potassium channels, GABAergic system, opioid receptors, NMDA receptors and posses a strong antioxidant effects through modulation of nitric oxide pathway, xanthine oxidase system and through leukocytic immobilization. Along with antiepileptic effect, flavanoids have also been observed to ameliorate memory deficit and mood disorders commonly associated with AEDs treatment. Based on the vast literature reports, an attempt has been made to collate the fragmented information available on flavonoids, to access there potential as antiepileptics for future. From this review it is cleared that, flavonoids open new encouraging perspectives for the antiepileptic treatment. A prospective randomized trial of flavonoids may be justified in humans.
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Ojewole JAO. Indigenous remedies and epilepsy:evaluation of some South African medicinal plants used as anticonvulsant remedies in Zulu folk medicine. J Blacpma Enero De 2005;4:1-21.
Yemadje LP, Houinato D, Quet F, Druet-Cabanac M, Preux PM. Understanding the differences in prevalence of epilepsy in tropical regions. J Epilepsia 2011;52:1376-81.
Macdonald RL, Kelly KM. Antiepileptic drug mechanisms of action. J Epilepsia 1995;36:S2-S12.
Czapinski P, Blaszczyk B, Czuczwar S J. Mechanisms of action of antiepileptic drugs. J Curr Top Med Chem 2005;5:3-14.
Rogawski MA. Diverse mechanisms of antiepileptic drugs in the development pipeline. J Epilepsy Res 2006;69:273-94.
Paulo AM, Maria AM, Marilisa MG, Carlos AM, Guerreiro. Phar-macovigilance in epileptic patients using antiepileptic drugs. J Arquivos de Neuro-Psiquiatria 2006;64:198-201.
Cramer JA, Mintzer S, Wheless J, Mattson RH. Adverse effects of antiepileptic drugs:a brief overview of important issues. J Ex-pert Rev Neurother 2010;10:885-91.
Wiebe S, Hesdorffer DC. Epilepsy:being ill in moreways than one. J Epilepsy Curr 2007;7:145-8.
Moshi MJ, Kagashe GA, Mbwambo ZH. Plants used to treat epilepsy by Tanzanian traditional healers. J Ethnopharmacol 2005;97:327-36.
Griebel G, Perrault G, Tan S, Shoemaker H, Sanger D. Pharmacological studies on synthetic flavonoids:comparison with diazepam. J Neuro-pharmacol 1999;38:965â€77.
Du XM, Sun NY, Takizawa N, Guo YT, Shoyama Y. Sedative and anticonvulsant activity of goodyerin, a flavonol glycoside from Goodyera schlechtendaliana. J Phytother Res 2002;16:261â€63.
Kavvadias D, Sand P, Youdim KA, Qaiser MZ, Riceâ€Evans C, Baur R, et al. The flavone hispidulin, a benzodiazepine receptor ligand with positive allosteric properties, traverses blood brain barrier and exhibits anticonvulsive effect. Br J Pharmacol 2004;142:811â€20.
Devi PU, Manocha A, Vohora D. Seizures, antiepileptics, anti-oxidants and oxidative stress:an insight for researchers. J Ex-pert Opin Pharmacother 2008;9:3169-77.
Fernandez SP, Wasowski C, Paladini AC, Marder M. Synergistic interaction between hesperidin, a natural flavonoid and diaze-pam. Eur J Pharmacol 2005;512:189-98.
Nijveldt RJ, Nood EV, Hoorn, Danny ECV, Boelens PG, Norren KV et al. Flavonoids:a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001;74:418-25.
Ibrahim G, Abdulmumin S, Musa KY, Yaro AH. Anticonvulsant activities of the crude flavonoid fraction of the stem bark of Fi-cus sycomorus (Moraceae). J Pharmacol Toxocol 2008;3:351-6.
Narayana KR, Reddy MS, Chaluvadi MR, Krishna DR. Bioflavonoids Classification, Pharmacological, Biochemical effects & Therapeutic potential. Indian J Pharmacol 2001;33:2-16.
Jager AK, Krydsfeldt K, Rasmussen HB. Bioassay-guided isola-tion of apigenin with GABA-benzodiazepine activity from Tanacetum parthenium. J Phytother Res 2009;23:1642-4.
Nicholson RA, David LS, Pan RL, Liu XM. Pinostrobin from Cajanus cajan (L.) Millsp. inhibits sodium channel-activated depolarization of mouse brain synaptoneurosomes. J Fi-toterapia 2010;81:826-9.
Yao Y, Han DD, Zhang T, Yang Z. Quercetin Improves Cognitive Deficits in Rats with Chronic Cerebral Ischemia and Inhibits Voltage-dependent Sodium Channels in Hippocampal CA1 Py-ramidal Neurons. J Phytother Res 2010;24:136-40.
Engelborghs S, Hooge RD, Deyn PPD. Pathophysiology of epi-lepsy. J Acta Neurol Belg 2000;100:201-13.
Cogolludo A, Frazziano G, Briones AM, Cobeno L, Moreno L, Federica L, et al. The dietary flavonoid quercetin activates BKCa currents in coronary arteries via production of H2O2;Role in vasodilatation. J Cardiovasc Res 2007;73:424-31.
Hanrahan JR, Chebib M, Johnston GA. Flavonoid modulation of GABAA receptors. Br J Pharmacol 2011;163(2):234-45.
Chebib M, Hinton T, Schmid KL, Brinkworth D, Qian H, Matos S, et al. Novel, potent, and selective GABAC antagonists inhibit myopia development and facilitate learning and memory. J Pharmacol Exp Ther 2009;328:448-57.
Goutman JD, Waxemberg MD, Oliver FD, Pomata PE, Calvo DJ. Flavonoid modulation of ionic currents mediated by GABAA and GABAC receptors. Eur J Pharmacol 2003;461:79-87.
Campbell EL, Chebib M, Johnston GAR. The dietary flavonoids apigenin and (-)-epigallocatechingallate enhance the positive modulation by diazepam of the activation by GABA of recombinant GABA(A) receptors. J Biochem Pharmacol 2004;68:1631-38.
Medina JH, Viola H, Wolfman C, Marder M, Wasowski C, Calvo D, et al. Overview-flavonoids:a new family of benzodiazepine receptor ligands. J Neurochem Res 1997;22:419-25.
Katavic PL, Lamb K, Navarro H, Prisinzano TE. Flavonoids as opioid receptor ligands:identification and preliminary struc-ture–activity relationships. J Nat Prod 2007;70:1278-82.
Subash S, Subramanian P. Morin a flavonoid exerts antioxidant potential in chronic hyperammonemic rats:a biochemical and histopathological study. J Mol Cell Biochem 2009;327:153-61.
Majewska M, Skrzycki M, Podsiad M, Czeczot H. Evaluation of antioxidant potential of flavonoids:an in vitro study. J Acta Pol Pharm 2011;68:611-15.
Ishige K, Schubert D, Sagara Y. Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. J Free Radical Bio Med 2001;30:433-46.
Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. J Free Radic Biol Med 1996;20:933-56.
Lien EJ, Ren S, Bui HH, Wang R. Quantitative structure-activity relationship analysis of phenolic antioxidants. J Free Radic Biol Med 1999;26:285-94.
Joshi D, Naidu PS, Singh A, Kulkarni SK. Protective effect of quercetin on alcohol abstinence-induced anxiety and convul-sions. J Med Food 2005;8:392-96.
Nassiri-Asl M, Shariati-Rad S, Zamansoltani F. Anticonvulsive effects of intracerebroventricular administration of rutin in rats. J Prog Neuropsychopharmacol Biol Psychiatry 2008;32:989-93.
Nassiri-Asl M, Mortazavi SR, Samiee-Rad F, Zangivand AA, Safdari F, Saroukhani S, et al. The effects of rutin on the development of pentylenetetrazole kindling and memory retrieval in rats. J Epilepsy Behav 2010;18:50-3.
An L, Zhang YZ, Yu NJ, Liu XM, Zhao N, Yuan L, et al. Role for serotonin in the antidepressant-like effect of a flavonoid extract of Xiaobuxin-Tang. J Pharmacol Biochem Behav 2008;89:572-80.
Hou Y, Aboukhatwa MA, Lei DL, Manaye K, Khan I, Luo Y. Antidepressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice. J Neuropharmacology 2010;58:911-20.
Middleton EJ. Effect of plant flavonoids on immune and in-flammatory cell function. J Adv Exp Med Biol 1998;439:175-82.
Hanasaki Y, Ogawa S, Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. J Free Radical Bio Med 1994;16:845-50.
Dehmlow C, Erhard J, de Groot H. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. J Hepatology 1996;23:749-54.
Shutenko Z, Henry Y, Pinard E. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion. J Biochem Pharmacol 1999;57:199-208.
Chang WS, Lee YJ, Lu FJ, Chiang HC. Inhibitory effects of flavo-noids on xanthine oxidase. J Anticancer Res 1993;13:2165-70.
Shoskes DA. Effect of bioflavonoids quercetin and curcumin on ischemic renal injury:a new class of renoprotective agents. J Transplantation 1998;66:147-52.
Cos P, Ying L, Calomme M. Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod 1998;61:71-6.
Bennett JP, Gomperts BD, Wollenweber E. Inhibitory effects of natural flavonoids on secretion from mast cells and neutro-phils. J Arzneimittelforschung 1981;31:433-37.
Friesenecker B, Tsai AG, Allegra C, Intaglietta M. Oral administration of purified micronized flavonoid fraction suppresses leukocyte adhesion in ischemia-reperfusion injury:in vivo observations in the hamster skin fold. Int J Microcirc Clin Exp 1994;14:50-5.
Friesenecker B, Tsai AG, Allegra C, Intaglietta M. Cellular basis of inflammation, edema and the activity of Daflon 500 mg. Int J Microcirc Clin Exp 1995;15:17-21.
Parfenova H, Carratu P, Tcheranova D, Fedinec A, Pourcyrous M, Leffler CW. Epileptic seizures cause extended postictal cerebral vascular dysfunction that is prevented by HO-1 overexpression. Am J Physiol Heart Circ Physiol 2005;288:H2843-H50.
Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. J Neuro Endocrinol Lett 2009a;30:470-76.
Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Increased 8-hydroxy-deoxyguanosine, amarker of oxidative damage to DNA, in major depression and myalgic en-cephalomyelitis / chronic fatigue syndrome. J Neuro Endocri-nol Lett 2009b;30:715-22.
Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Lower plasma coenzyme Q10 in depression:a marker for treatment resistance and chronic fatigue in depres-sion and a risk factor to cardiovascular disorder in that illness. J Neuro Endocinol Lett 2009c;30:462-69.
Ohmori H, Kanayama N. Immunogenicity of an inflammation-associated product, tyrosine nitrated self-proteins. J Autoim-mun Rev 2005;4:224-29.
Rodriguez-Mora OG, Howe CJ, Lahair MM, McCubrey JA, Franklin RA. Inhibition of CREB transcriptional activity in human T lymphocytes by oxidative stress. J Free Radical Bio Med 2005;38:1653-61.
Kolosova NG, Shcheglova TV, Sergeeva SV, Loskutova LV. Long-Term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent accelerated OXYS rats. J Neurobiol Aging 2006;27:1289-97.
Abdul HM, Butterfield DA. Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and α-lipoic acid against HNE-mediated oxidative stress and neurotoxicity:Implications for Alzheimer's disease. J Free Radical Bio Med 2007;42:371-84.
Clausen A, Doctrow S, Baudry M. Prevention of cognitive defi-cits and brain oxidative stress with superoxide dismutase/ catalase mimetics in aged mice. J Neurobiol Aging 2010;31:425-33.
Michael J. Oxidative stress and cognitive longevity. J Nutrition 2010;26:595-603.
Vauzour D, Vafeiadou K, Mateos AR, Rendeiro C, Spencer JPE. The neuroprotective potential of flavonoids:a multiplicity of effects. J Genes Nutr 2008;3:115-26.
Spencer JP. The interactions of flavonoids within neuronal signalling pathways. J Genes Nutr 2007;2:257-73.
Biegon A, Greenberger V, Segal M. Quantitative histochemistry of brain acetylcholineesterase and learning in the aged rat. J Neurobiol Aging 1986;7:215â€7.
Perry EK. Cholinergic component of cognitive impairment in dementia. In:Burns A, Levy R, editors. London:Dementia, Chapman and Hall;1994.p.36-48.
Kish SJ, Olivier A, Dubeau F, Robitaille Y, Sherwin AL. Increased activity of choline acetyltransferase and acetylcholinesterase in actively epileptic human cerebral cortex. J Epilepsy Res 1988;2:227-23.
Serra M, Dazzi L, Cagetti E, Chessa MF, Pisu MG, Sanna A, et al. Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats. J Neurochem 1997;68:313-18.
Pepeu G, Giovannini MG. Cholinesterase inhibitors and memo-ry. J Chem Biol Interact 2010;187:403-08.
Adewusi EA, Moodley N, Steenkamp V. Antioxidant and acetyl-cholinesterase inhibitory activity of selected southern African medicinal plants. S Afr J Bot 2011;77:638-44.
Katalinic M, Rusak G, Domacinovic Barovic J, Sinko G, Jelic D, Antolovic R, et al. Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase. Eur J Med Chem 2010;45:186-92.
Messaoudi M, Bisson JF, Nejdi A, Rozan P, Javelot H. Antide-pressant-like effects of a cocoa polyphenolic extract in Wistare Unilever rats. J Nutr Neurosci 2008;11:269-76.
Zhao Z, Wang W, Guo H, Zhou D. Antidepressant-like effect of liquiritin from Glycyrrhiza uralensis in chronic variable stress induced depression model rats. J Behav Brain Res 2008;194:108-13.
Yi LT, Li CF, Zhan X, Cui CC, Xiao F, Zhou LP, et al. Involvement of monoaminergic system in the antidepressant-like effect of the flavonoid naringenin in mice. J Prog Neuropsychopharma-col Biol Psychiatry 2010;34:1223-28.
Luo L, Sun Q, Mao YY, Lu YH, Tan RX. Inhibitory effects of flavo-noids from Hypericum perforatum on nitric oxide synthase. J Ethnopharmacol 2004;93:221-25.
Xiukun W, Lujun Z, Lei H, Dongming X, Lijun DU. Effect of flavo-noids in Scutellariae Radix on depression-like behavior and brain rewards:possible in dopamine system. J Tsing Sci and Tech 2010;15:460-66.
Choudhary N, Bijjem KR, Kalia AN. Antiepileptic potential of flavonoids fraction from the leaves of Anisomeles malabarica. J Ethnopharmacol 2011;135:238-42.
Maurya SK, Raj K, Srivastava AK. Antidyslipidaemic activity of Glycyrrhiza glabra in high fructose diet induced dyslipidaemic Syrian golden hamsters. Indian J Clin Biochem 2009;24:404-40.
Ambawade SD, Kasture VS, Kasture SB. Anticonvulsant activity of roots and rhizomes of Glycyrrhiza glabra. Indian J Pharmacol 2002;34:251-55.
Speroni E, Minghetti A. Neuropharmacological activity of ex-tracts from Passiflora incarnata. J Planta Med 1988;54:488-91.
Wolfman C, Viola H, Paladini A, Dajas F, Medina JH. Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. J Pharmacol Biochem Behav 1994;47:1-4.
Dhawan K, Dhawan S, Sharma A. Passiflora:a review update. J Ethnopharmacol 2004;97:1-23.
Zhang Z, Lian XY, Li S, Stringer JL. Characterization of chemical ingredients and anticonvulsant activity of American skullcap (Scutellaria lateriflora). J Phytomedicine 2009;16:485-93.
Park HG, Yoon SY, Choi JY, Lee GS, Choi JH, Shin CY, et al. Anti-convulsant effect of wogonin isolated from Scutellaria baicalensis. Eur J Pharmacol 2007;574:112-9.
Wang H, Hui KM, Chen Y, Xu S, Wong JT, Xue H. Structure–activity relationships of flavonoids, isolated from Scutellaria baicalensis, binding to benzodiazepine site of GABAA receptor complex. J Planta Med 2002;68:1059-62.
Cho J, Lee HK. Wogonin inhibits excitotoxic and oxidative neu-ronal damage in primary cultured rat cortical cells. Eur J Phar-macol 2004;485:105-10.
Liu LY, Wei EQ, Zhao YM, Chen FX, Wang ML, WP Zhang, et al. Protective effects of baicalin on oxygen/glucose deprivation and NMDA-induced injuries in rat hippocampal slices. J Pharm Pharmacol 2005;57:1019-26.
Ayuga C. Contribution to study of flavonoids in Drosera rotundifolia. J L An R Acad Farm 1985;51:321-6.
Hema B, Bhupendra S, Mohamed STS, Gauthaman K. Anticon-vulsant effect of Drosera burmannii Vahl. Int J Appl Res Nat Prod 2009;2:1-4.
Manigauha A, Patel S. Anticonvulsant study of Pongamia pinnata Linn against PTZ induced convulsion in rats. Int J of Pharm and Bio Sci 2010;1:1-4.
Tan Z. Neural protection by naturopathic compounds-an example of tetramethylpyrazine from retina to brain. J Ocul Boil Dis Inform 2009;2:57-64.
Mishra A, Bhatti R, Singh A, Ishar MPS. Ameliorative effect of cinnamon oil from Cinnamomum zeylanicum upon early stage of diabetic nephropathy. J Planta Med 2010;76:412-7.
Ali A, Rao NV, Shalam MD, Gouda TS, Shantakumar SM. Anti-convulsive Effect of Seed Extract of Caesalpinia bonducella (Roxb.). Iran J Pharmacol Therp 2009;8:51-5.
Gupta M, Mazumdar UK, Bhawal SR. CNS activity of Vitex ne-gundo Linn. in mice. Indian J Exp Biol 1997;37:143-6.
Tandon VR. Medicinal uses and biological activities of Vitex negundo. J Nat Prod Rad 2005;4:162-5.
Gupta RK, Tandon VR. An experimental evaluation of anticon-vulsant activity of Vitex negundo. Indian J Physiol Pharmacol 2005;49:199-205.
Vieira RF, Grayer RJ, Paton A, Simon JE. Genetic diversity of Ocimum gratissimum L. based on volatile oil constituents, flavonoids and RAPD markers. J Biochem Syst Ecol 2001;29:287-304.
Okoli CO, Ezike AC, Agwagah OC, Akah PA. Anticonvulsant and anxiolytic evaluation of leaf extracts of Ocimum gratissimum, a culinary herb. J Phcog Res 2010;2:36-40.
Jamil SS, Nizami Q, Salam M. Centella asiatica linn. Urban oA Review. J Nat Prod Rad 2007;6:158-70.
Visweswari G, Siva PK, Lokanatha V, Rajendra W. The antiepi-leptic effect of Centella asiatica on the activities of Na+, K+-ATPase, Mg2+-ATPase, and Ca2+-ATPase in rat brain during pentylenetetrazol-induced epilepsy. Indian J Pharmacol 2010;42:82-6.
Beltrame F, Ferreira A, Cortez D. Coumarin glycoside from Cissus sicyoides. J Nat Prod Lett 2002;16:213-6.
de Almeida ER, Rafael KR, Couto GB, Ishigami AB. Anxiolytic and anticonvulsant effects on mice of flavonoids, linalool, and alpha-tocopherol presents in the extract of leaves of Cissus sicyoides L. (Vitaceae). J Biomed Biotechnol 2009;2009:1-6.
Dhanasekaran S, Palayan M. Sedative and anticonvulsant activities of the methanol leaf extract of Ficus hispida Linn. J Drug Inven Today 2009;1:23-7.
Vyawahare NS, Bodhankar SL. Anticonvulsant activity of Ar-gyreia speciosa in mice. Indian J Pharm Sci 2009;71:131-4.
Joshi H, Kaur N, Chauban J. Evaluation of Nootropic effect of Argyreia speciosa in mice. J Health Sci 2007;53:382-8.
Arote SR, Yeole PG. Pongamia pinnata L:A Comprehensive Review. Int J Pharm Tech Res 2010;2:2283-90.
Manigauha A, Patel S. Anticonvulsant study of Pongamia pinnata Linn against PTZ induced convulsion in rats. Int J Pharm Bio Sci 2010;1:1-4.
Gupta M, Shaw BP. Uses of medicinal plants in Panchakarma ayurvedic therapy. IJTK 2009;8:372-8.
Matlawska I, Silkorska M. Flavonoid compounds in the flowers of Abutilon indicum (Linn.) Sweet. Acta Pol Pharm 2002;59:227â€9.
Golwala DK, Patel LD, Vaidya SK, Bothara SB, Mani M, Patel P. Anticonvulsant activity of Abutilon indicum leaf. Int J Pharmacy Pharm Sci 2010;2:66-71.
Vattikuti UMR, Ciddi V. An overview on Hypericum perforatum Linn. J Nat Prod Rad 2005;4:368-81.
Vyawahare NS, Khandelwal AR, Batra VR, Nikam AP. Herbal anticonvulsants. J Herb Med Toxicol 2007;1:9-14.
Hosseinzadeh H, Karimi GR, Rakhshanizadeh M. Anticonvulsant effect of Hypericum perforatum:role of nitric oxide. J Ethnopharmacol 2005;98:207-8.
Bum EN, Dawacka DL, Schmutzb M, Rakotonirinac A, Rakotonirinac SV, Portetb C, et al. Anticonvulsant activity of Mimosa pudica decoction. J Fitoterapia 2004;75:309-14.
Sutar NG, Sutar UN, Behera. Antidiabetic activity of the leaves of Mimisa pudica Linn in albino mice. J Herb Med Toxicol 2009;3:123-6.
Silambujanaki P, Chitra V, Kumari S, Sankari M, Raju D, Tejo B, et al. Anti-convulsant activity of methanolic extract of Butea monosperma leaves. Res J Pharm Bio Chem Sci 2010;1:431-5.
Bum EN, Taiwe GS, Moto FCO, Ngoupaye GT, Nkantchoua GCN, Pelanken MM, et al. Anticonvulsant, anxiolytic, and sedative properties of the roots of Nauclea latifolia Smith in mice. J Epi-lepsy Behav 2009;15:434-40.
Galani VJ, Patel BG. Effect of hydoalcoholic extract of Sphaeranthus indicus against experimentally induced anxiety, depression, convulsions in rodents. Int J Ayurveda Res 2010;1:87-92.
Ravi V, Saleem TSM, Maiti PP, Gauthaman K, Ramamurthy J. Phytochemical and pharmacological evaluation of Solanum ni-grum. Afr J Pharm Pharacol 2009;3:454-7.
Sankari M, Chitra V, Silambujanaki P, Raju D. Anticonvulsant activity of ethanolic extract of Aegle marmelos (Leaves) in mice. Int J Pharm Tech Res 2010;2:640-3.
Saberi M, Rezvanizadeh A, Bakhtiarian A. The antiepileptic activity of Vitex agnus castus extract on amygdala kindled sei-zures in male rats. J Neurosci Lett 2008;441:193-6.
Hajdu Z, Hohmann J, Forgo P, Martinek T, Dervarics M, Zupko I, et al. Diterpenoids and flavonoids from the fruits of Vitex ag-nus-castus and antioxidant activity of the fruit extracts and their constituents. J Phytother Res 2007;21:391-4.
Sasaki K, Hatta S, Wada K, Ohshika H. Bilobalide prevents re-duction of γ-aminobutyric acid levels and glutamic acid decar-boxylase activity induced by 4-O-methylpyridoxine in mouse hippocampus. J Life Sci 2000;67:709-15.
Sasaki K, Wada K, Hatta S, Ohshika H, Haga M. Bilobalide, a constituent of Ginkgo biloba L., potentiates drug-metabolizing enzyme activities in mice:possible mechanism for anticonvul-sant activity against 4-O-methylpyridoxine-induced convul-sions. J Res Commun Mol Pathol Pharmacol 1997;96:45-56.
Heim KE, Tagliaferro AR, Bobilzya DJ. Flavonoid antioxi-dants:chemistry, metabolism and structure-activity relation-ships. J Nutr Biochem 2002;13:572-84.
Ivetic V, Popovic M, Naumovic N, Radenkovic M, Vasic V. The effect of Ginkgo biloba (EGb 761) on epileptic activity in rab-bits. J Molecules 2008;13:2509-20.
Bandyopadhyay SK. Ischaemia induced oxidative stress in brain and its management with natural anti-oxidants. Bomb Hosp J 2009;51:460-71.
Kaushik D, Tripathi A, Tripathi R, Ganachari M, Khan SA. Anti-convulsant activity of Bacopa monniera in rodents. Braz J Pharm Sci 2009;45:643-9.
Mathewa J, Paula J, Nandhua MS, Paulose CS. Bacopa monnieri and Bacoside-A for ameliorating epilepsy associated behavioral deficits. J Fitoterapia 2010;81:315-22.
Raja AE, Vijayalaksshmi M, Devalarao G. Acorus calamus Linn:Chemistry and Biology. Res J Pharm and Tech 2009;2:256-61.
Jayaraman R, Anitha T, Joshi VD. Analgesic and anticonvulsant effects of Acorus calamus roots in mice. Int J of Pharm Tech Res 2010;2:552-5.
Dragoeva AP, Nanova ZD, Kalcheva VK. Allelopathic activity of micropropagated Origanum vulgare ssp. hirtum and its effect on mitotic activity. J Allelopathy 2008;22:131-42.
Gupta M, Mazumdar UK, Chakrabrati S. CNS activities of me-thanolic extract of Moringa oleifera root in mice. J Fitoterapia 1999;70:244-50.
Rastogi T, Bhutda V, Moon K, Aswar PB, Khadabadi SS. Com-parative studies on anthelmintic activity of Moringa oleifera and Vitex negundo. Asian J Res Chem 2009;2:181-2.
Singh D, Singh SK, Maurya VB, Prajapati K, Kumar H, Niranjain PS, et al. Evaluation of anticonvulsant activity of the leaves ethanolic and aqueous extracts of Nyctanthes arbortristis Linn. against seizures induced by PTZ and electroconvulsive shock in mice. Int J Pharm Sci Res 2010;1:63-71.
Lee SJ, Chung HY, Maier CGA, Wood AR, Dixon RA, Mabry TJ. Estrogenic Flavonoids from Artemisia vulgaris L. J Agric Food Chem 1998;46:3325-29.
Yadava RN, Madhu S, Reddy V. A new biologically active flavo-nol glycoside from the seeds of Abrus precatorius Linn. J Asian Nat Prod Res 2002;4:103-7.
He X, Lian L, Lin L, Bernart MW. High-performance liquid chromatography-electrospray mass spectrometry in phyto-chemical analysis of sour orange (Citrus aurantium L.). J Chro-matogr A 1997;791:127-34.
Dimpfel W. Different anticonvulsive effects of hesperidin and its aglycone hesperetin on electrical activity in the rat hippo-campus in vitro. J Pharm Pharmacol 2006;58:375-79.
Mahmoodi M, Zohoor A, Asadi M. Anticonvulsant effect of sour orange flowers extract in experimental pentylenetetrazol-induced seizures in rat. J Arch Iranian Med 2003;6:212-3.
Chauhan AK, Dobhal MP, Joshi BC. A review of medicinal plants showing anticonvulsant activity. J Ethnopharmacol 1988; 22:11-23.
Rasilingam D, Duraisamy S, Subramanian R. Anticonvulsant activity of bioflavonoid gossypin. Bangladesh J Pharmacol 2009;4:51-4.
Costello DJ, Delanty N. Oxidative injury in epilepsy:potential for antioxidant therapy? J Expert Rev Neurother 2004;4:541-53.
Oliver CN, Starve-Reed PE, Stadtman ER, Floyd RA. Oxidative damage to brain proteins, loss of free radicals during ischemia/ reperfusion induced injury to gerbil brain. J Proct Natt Acad Sci USA 1990;87:5144-47.
Halliwell RF, Davey PG, Lambert JJ. The effects of quinolones and NSAIDs upon GABA-evoked currents recorded from dorsal root ganglion neurones. J Antimicrob Chemother 1991;27:209-18.
Patel MN. Oxidative stress, mitochondrial dysfunction and epilepsy. J Free Radic Res 2002;6:1139-46.
Chimakurthy J, Murthy TEGK, Upadhyay L. Effect of Curcumin on sub-therapeutic doses of AED’s and long term memory in mice induced GTC type of seizures in rats. Res J Pharm and Tech 2008;1:401-4.
Kumar A, Dogra S, Prakash A. Protective effect of curcumin (Curcuma longa), against aluminium toxicity:Possible beha-vioral and biochemical alterations in rats Behavioural. J Brain Res 2009;205:384-90.
Mehla J, Reeta KH, Gupta P, Gupta YK. Protective effect of cur-cumin against seizures and cognitive impairment in a pentyle-netetrazole-kindled epileptic rat model. J Life Sci 2010;87:596-603.
Sharma V, Nehru B, Munshi A, Sharma S, Khanna P. Protective effect of curcumin in behavioral impairment induced by Penty-lenetetrazole in rats. J Pharm Res 2011;4:11-4.
Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C. Interaction between flavonoids and the blood-brain barrier:in vitro studies. J Neurochem 2003;85:180-92.
Galati G, O'Brien PJ. Potential toxicity of favonoids and other dietary phenolics:significance for their chemopreventive and anticancer properties. J Free Radic Biol Med 2004;37:287-303.