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DISCUSSION Karunakar Hegde et al Evaluation of Anticonvulsant Activity of Carissa spinarum Root Extract GABA is the major inhibitory neurotransmitter in the brain where as glutamic acid is an excitatory neurotransmitter in the brain. The inhibition of GABA neurotransmitter and the enhancement of the action of glutamic acid have been 13 shown to be the underlying factors in epilepsy . Our study shows that the ethanol extract of the roots of C. spinarum protected some of the animals against seizures induced by maximal electroshock, pentylenetetrazole and also delayed the latency of the seizures. In the present study maximal electroshock produced seizures in all the animals used. It has often been stated that antiepileptic drugs that block MES-induced tonic extension act by blocking seizure spread. Moreover, drugs that inhibit voltage-dependent Na+ channels, such as phenytoin can 14 prevent MES-induced tonic extension . However, phenobarbitone is as effective against electrically induced convulsion as it is against pentylenetetrazole-induced convulsions in mice and phenobarbitone is known to reduce the electrical activity of neurons within a chemically induced epileptic focus in the cortex, where as diazepam does not suppress the focal activity but prevents it from 15, 16 spreading . Though, diazepam had anticonvulsant effect on both PTZ-induced seizures and maximal electroshockinduced seizures, in which diazepam effect for the former (100% prevention) is better than the latter (50% prevention). This is consistent with the report that benzodiazepine (BDZ) agonists such as diazepam, etc. are more potent in the prevention of PTZ-induced seizures than in that of MES- 17 induced tonic seizures . In the present study, pentylenetetrazole was shown to induce seizures in all the mice used. Pentylenetetrazole may be 18 producing seizures by inhibiting gabaergic mechanisms . Standard antiepileptic drugs diazepam and phenobarbitone are thought to produce its effects by enhancing GABAmediated inhibition in the brain. It is therefore possible that the anticonvulsant effects shown in this study by the said drug against seizures produced by PTZ might be due to the activation of GABA neurotransmission. Since ethanol extract of the roots of C. spinarum similarly antagonized seizures elicited by pentylenetetrazole in mice, it is probable therefore that it may also be exerting its anticonvulsant effects by affecting gabaergic mechanisms. In the same study, picrotoxin also produced seizures in all the mice used. Picrotoxin has been shown to elicit seizures, by antagonizing the effect of GABA by blocking the chloride 13 channels linked to GABA -receptor . In this study, A diazepam and phenobarbitone were shown to antagonize 67 the effect of picrotoxin and ethanol extract of C. spinarum was also shown to delay the latency of picrotoxin–induced seizures, suggesting that ethanol extract of the roots of C. spinarum may be affecting gabaergic mechanisms, probably by opening the chloride channels associated with GABAreceptors. Triterpenic steroids and triterpenoidal saponins are reported to possess anticonvulsant activity in some 19, 20 experimental seizure models like MES, PTZ . Some monoterpenes, flavonoids also have protective effects against 21, 22 PTZ and picrotoxin-induced convulsions . It is worthwhile to isolate the bioactive principles, which are responsible for these activities, which is in progress in our laboratory. These findings justify traditional use of this plant in the control and /or treatment of convulsions, epilepsy and validate its claim of being used for the said purpose in folklore medicine. CONCLUSION It can be concluded that the data obtained in the present study suggest that the ethanol extract of the roots of C. spinarum may said to be possess significant anticonvulsant activity via non-specific mechanisms, since it has been shown to delay the latency of seizures produced by the convulsive models which affecting electrical discharge in the brain, gabaergic system and glutaminergic systems and also which may be of potential benefit for the management, control and /or treatment of convulsions and epileptic disorders. REFERENCES 1. Farnsworth NR. Screening plants for new medicines. In: Wilson EO, editor, Biodiversity, part II, National Academy Press, Washington, 1989, pp 83-97. 2. Kirtikar KR, Basu BD. Indian Medicinal Plants, Vol. II, Lalit Mohan Basu, Allahabad, 2003,1548-1549. 3. Raina MK, Bhatnaga JK, Atal CK. Isolation of caffeic acid from the roots of Carissa spinarum Linn, The Indian J Pharm, 1971;33:76-7. 4. Mathuram V, Brahmadhayalaselvam A, Hussain AJ, Rao RB, Patra A. Chemical constituents of Carissa spinarum and their antibacterial activity, J Indian Chem Soc, 1998;75:262-4. 5. Rastogi RC, Kulshreshtha DK, Rastogi RP. Cardioactive constituents from Carissa spinarum Linn, Indian J Chem, 1969;7:1102-4. 6. Rao RJ, Kumar US, Reddy SV, Tiwari AK, Rao JM. Antioxidants and a new germacrane sesquiterpene from Carissa spinarum, Nat Prod Res, 2005;19:763-9. RJPS, Apr-Jun, 2011/ Vol 1/ Issue 1
Karunakar Hegde et al Evaluation of Anticonvulsant Activity of Carissa spinarum Root Extract 7. Vohra MM, De NN. Comparative cardiotonic activity of Carissa carandas and Carissa spinarum, Indian J Med Res, 1963;51:937-40. 8. Bhakuni DS, Dhar ML, Dhar MM, Dhawan BN, Gupta B, Srimal RC. Screening of Indian plants for biological activity: Part 3, Indian J Exptl Biol, 1971;9:91-102. 9. Harbone JB. Phytochemical methods. A Guide to Modern nd Techniques of Plant Analysis. 2 Ed, Chapman and Hall, London, 1984, pp 84-274. 10. OECD, Guidelines for testing of chemicals, Acute oral toxicity, Environmental Health and Safety Monograph Series on Testing and Adjustment No. 425, 2001,1. 11. Swinyard EA. Laboratory evaluation of antiepileptic drugs. Review of Laboratory methods, Epilepsia, 1969;10:107-19. 12. Vellucci SV, Webster RA. Antagonism of caffeine-induced seizures in mice by Ro 15-1788, Eur J Pharmacol, 1984;97:289-95. 13. Westmoreland BF, Benarroch EE, Dube JR, Regan TJ, Sandok BA. Medicinal neurosciences, Rochester: Margo Foundation, 1994, pp 307-12. 14. Rogawski MA, Porter RJ. Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising development stage compounds, Pharmacol Rev, 1990;42:223-86. 15. Levy RH, Mattson RH, Meldrum BS, Driefuss FE, Penry JK. th Antiepileptic drug. 4 Ed, Raven Press, New York, 1995. 68 16. Meldrum BS. Update on the mechanism of action of antiepileptic drugs, Epilepsia, 1996;37:S4-S11. 17. Krall RL, Penry JK, White BG, Kupferberg HJ, Swinyard EA. Antiepileptic drug development: II. Anticonvulsant drug screening, Epilepsia, 1978;19:409-28. 18. De Sarro A, Cecchetti V, Fravoloni V, Naccari F, Tabarrinia O, De Sarro G. Effects of novel6-desfluoroquirolones and classic quinolones on pentylenetetrazole-induced seizure in mice, Antimicrob Agents Chemother, 1999; 43:1729-36. 19. Kasture VS, Kasture SB, Chopde CT. Anticonvulsive activity of Butea monosperma flowers in laboratory animals, Pharmacol Biochem Behav, 2002;72:965-72. 20. Chauhan AK, Dobhal MP, Joshio BC. A review of medicinal plant showing anticonvulsant activity, J Ethnopharmacol, 1988;22:11-23. 21. Librowski T, Czarnecki R, Mendyk A, Jastrzebska M. Influence of new monoterpenes homologues of GABA on the central nervous system activity in mice, Poland J Pharmacol, 2000;52:317-21. 22. Brum LF, Elisabetsky E, Souza D. Effects of linalool on [(3) H] MK801 and [(3) H] muscimol binding in mouse cortical membranes, Phytother Res, 2001;15:422-5. Address for Correspondence Karunakar Hegde, Department of Pharmacology, Srinivas College of Pharmacy, Valachil, Post - Parangepete, Mangalore- 574 143, Karnataka, India. E-mail: khegde_sh2003@yahoo.co.in RJPS, Apr-Jun, 2011/ Vol 1/ Issue 1
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R G U H S Dr. Divakar Goli Principa
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RGUHS Journal of Pharmaceutical Sci
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Dear Readers, Rajiv Gandhi Universi
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RGUHS Journal of Pharmaceutical Sci
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