Effect of Ethanolic Extract of Indigofera tinctoria on Chemically-Induced Seizures and Brain GABA Levels in Albino Rats

Document Type : Original Article


1 Department of Pharmacy, SPW Polytechnic, Tirupati – 517 502, India

2 Faculty of Pharmaceutical Sciences, UCSI University, Menara Gading, UCSI Heights, 56000 Kuala Lumpur, Malaysia

3 Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (A Women’s University), Tirupati - 517 502, India


Indigofera tinctoria Linn. of Fabaceae family is claimed to be useful to control epileptic seizures in the Indian system of folkore medicine. This study was designed to evaluate I. tinctoria and to verify the claim. Materials and Methods
Seizures were induced in male albino rats with pentylenetetrazole (PTZ). The test group animals were administered ethanolic extract of Indigofera tinctoria (EEIT) orally. The time of onset and duration of clonic convulsions were recorded. Maximal electroshock seizures (MES) were induced in animals. The duration of hind limb tonic extension (HLTE) was recorded. GABA levels and GABA transaminase activity in brain were estimated.
In PTZ model, EEIT significantly (P< 0.01, P< 0.001) delayed the onset of convulsions and reduced the duration of seizures in a dose dependent manner. A significant (P< 0.05) reduction in the duration of HLTE at higher doses of EEIT was observed in MES model. Increase in brain GABA levels was observed on treatment with EEIT at 500 and 1000 mg/kg doses, suggested that the plant may be acting by facilitating GABAergic transmission. A significant reduction (P< 0.05) in the activity of brain GABA transaminase was observed at higher doses. No neurotoxic signs were observed with rotarod test, pentobarbital induced sleeping time, locomotor activity and haloperidol-induced catalepsy.
The ethanolic extract of I. tinctoria was found to be useful to control and treat the variety of seizures.


1. Steve White H. Preclinical development of antiepileptic drugs: Past, Present and future directions. Epilepsia 2003; 44: 2-8.
2. Sigel E, Buhr A. The benzodiazepine binding site of GABAA receptors. Trends Pharmacol Sci 1997; 18: 425-429.
3. Sieghart W, Sperk G. Subunit composition, distribution and function of GABAA receptor subtypes. Curr Top Med Chem 2001; 2:795-816.
4. Raza M, Choudhary MI, Atta-ur-Rahman. Anticonuilsant medicinal plants. In: Atta-ur-Rahman, editor. Studies in Natural Product Chemistry. Netherlands:Elsevier Science Publishers; 1999. Vol. 22. p. 507-553.
5. Kumar SA, Mohan ME, Gandhimathi R, Amuda P. Study on the anti-seizure activity of methanolic extracts of Indigofera tinctoria (L). Pharmacologyonline 2009; 1:1341-1351.
6. Swinyard EA, Woodhead JM. Experimental detection, quantification and evaluation of anticonvulsants. In: Woodbury DM, Penry JK, Pippenger CE. Epileptic drugs.New York: Ravenpress;1982. p.111-126.
7. Mohammad S, Leila N, Mohammad K. Anticonvulsant activity and chemical composition of Artemisia dracunculus L. essential oil. J Ethnopharmacol 2004; 94:283-287.
8. Kanuranakar H, Shalin PT, Arun BJ, Shastry CS, Chandrashekhar KS. Anticonvulsant activity of Carissa carandas Linn. Root extraction in experimental mice. Trop J Pharmaceutical Res? 2009; 8: 117-125. 
9. Mohammad S, Ali M, Mohammad K. Evaluation of anticonvulsant activity of the seed acetone extract of Ferula gummosa Boiss. against seizures induced by pentylenetetrazole and electroconvulsive shock in mice. J Ethnopharmacol 2002; 82:5-109.
10. Schmutz M, Portet Ch, Jeker A, Klebs K, Vassout A, Allgeier H, Heckendorn R, Fagg GE, Olpe HR, Riezen H. The competitive NMDA receptor antagonists CGP37849 and CGP39551 are potent, orally-active anticonvulsants in rodents. Archives of .Pharmacol 1990; 342:61-66.
11. Swinyard EA. Laboratory evaluation of antiepileptic drugs. Review of laboratory methods. Epilepsia 1969; 10:107-119.
12. Deshmane DN, Gadgoli HC, Halade VG. Anticonvulsant effect of Origanm majorana L. Pharmacologyonline 2007; 1:64-78.
13. Khuhawar MY, Rajper AD. Liquid chromatographic determination of y-aminobutyric acid in cerebrospinal fluid using 2-hydroxynaphthaldehyde as derivatizing reagent. J Chromatogr B 2003; 788:413-418.
14. Nayak P, Chatterjee AK. Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat. Neurosci 2003; 4:1-8.
15. Rao VS, Rao A, Karanth KS. Anticonvulsant and neurotoxicity profile of Nardostachys jatamansi in rats. J Ethnopharmacol 2005; 102:351-356.
16. Sander JW. The epidemiology of epilepsy revisited. Curr Opin Neurol 2003; 16:165-170.
17. MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain 2000; 123: 665-676.
18. Forsgren L, Beghi E, Oun A, Sillanpaa M. The epidemiology of epilepsy in Europe: a systematic review. Eur J Neurol 2005; 12:245-253.
19. Brodie MJ, Lerche H, Gil-Nagel A, Hall S, Shin P, Nohria H. Efficiency and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology 2010; 75:1817-1824.
20. Stephen LJ, Brodie MJ. Pharmacotherapy of epilepsy: newly approved and developmental agents. CNS Drugs 2011; 25:89-107.
21. Rauca C, Zerbe R, Jantze H. Formation of free hydroxyl radicals after PTZ-induced seizure and kindling. Brain Res 1999; 847:347-351.
22. El-Tahir KE, Ashour MM, Al-Harbi MM. The cardiovascular actions of volatile oil of the black seeds (Nigella sativa) in guinea-pigs: elucidation of the mechanism(s) of action. Gen pharmacol 1993; 24:1123-1131.
23. Fisher RS. Animal models of the epilepsies. Brain Res Rev 1989; 14:245-278.
24. Stefani A, Spadoni F, Giacomini P, Lavaroni F, Bernardi G. The effects of gabapentin on different ligand- and voltage-gated currents in isolated cortical neurons. Epilepsy Res 2001; 43:239-248.
25. Patten D, Foxon GR, Martin KF, Hallwell RF. An electrophysiological study of the effects of propofol on native neuronal ligand-gated ion channels. Clin Exp Pharmacol Physiol 2001; 28:451-458.
26. Subramaniam S, Rho JM, Penix L, Donevan SD, Fieldin RP, Rogawski MA. Felbamate block the N-methyl-D- aspartame receptor. J Pharmacol Exp Ther 1995; 273:878-886.
27. Wickenden AD, Weifeng YU, Jegla T, Wagoner PK. Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol 2000; 58:591-600.
28. Macdonald RL, Kelly KM. Antiepileptic drugs mechanisms of action. Epilepsia 1995; 36:S2-S12.
29. Nayak P, Chatterjee AK. Effects of aluminium exposure on brain glutamate and GABA systems; an experimental study in rats. Food Chem Toxicol 2001; 39:1285-1289.
30. Singh D, Goel RK. Anticonvulsant effect of Ficus religiosa: Role of serotonergic pathways. J Ethnopharmacol 2009; 123:330-334.