Anticonvulsant, Anxiolytic and Neurotoxicity Profile of Aqarqarha (Anacyclus pyrethrum) DC (Compositae) Root Ethanolic Extract

Syed Mohd Abbas Zaidi, Shadab Ahmad Pathan, Surender Singh, Shakir Jamil, Farhan Jalees Ahmad, Roop Krishen Khar

Department of Moalajat, HSZH Govt. Unani Medical College, Bhopal, India.
Department of Moalijat, Faculty of Medicine (Unani), Jamia Hamdard & CCRUM, New Delhi, India..
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India;.
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India;.

DOI: 10.4236/pp.2013.47077                

Abstract

Ethnopharmacological relevance: Aqarqarha (Anacyclus pyrethrum) DC root has long been used as a traditional an-tiepileptic remedy in Unani system of medicine over centuries. Aim of the Study: To rationalize the ethnomedical claim and screen for anxiolytic and neurotoxicity profile of ethanolic extract of Aqarqarha (Anacyclus pyrethrum) root (APE). Materials and Methods: The anticonvulsant and anxiolytic potential of APE (100-800 mg/kg) was evaluated against Pentylenetetrazole (PTZ), Bicuculline (BCL), Increasing current electroshock (ICES) and Elevated plus maze(EPM) models. Rotarod test was employed as neurotoxicity model including an additional higher dose (1600 mg/kg). Results: The APE showed significant anticonvulsant activity (p < 0.001) against PTZ (70 mg/kg, i.p.) in a dose-dependent manner but against BCL (30 mg/kg, i.p.) at the dose 800 mg/kg only (p < 0.001). However, it did not protect animals against ICES induced seizures (p > 0.05). The extract also showed anxiolytic behaviour in EPM (p < 0.001) and impaired motor coordination only at 1600 mg/kg in rotarod performance. HPTLC of the extract confirmed the presence of eugenol in the extract. Conclusions: The results suggested significant anticonvulsant activity of APE against PTZ and BCL but failure against ICES. Moreover, APE also exhibited anxiolytic potential without any evidence of neurotoxicity at the effective dose level. We concluded that anticonvulsant effect of APE is probably mediated by enhancing GABAergic neurotransmission.

Keywords

Aqarqarha; HPTLC; Epilepsy; Aqarqarha (Anacyclus pyrethrum)

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	J. W. Sander and S. D. Shorvon, “Epidemiology of the Epilepsies,” Journal of Neurology Neurosurgery & Psychiatry, Vol. 61, No. 5, 1996, pp. 433-443. http://dx.doi.org/10.1136/jnnp.61.5.433
[2]	N. Senanayake and G. C. Roman, “Epidemiology of Epilepsies in Developing Countries,” WHO Bulletin, Vol. 71, No. 2, 1993, pp.247-258.
[3]	O. Devinsky, “Cognitive and Behavioral Effects of Antiepileptic Drugs,” Epilepsia, Vol. 36, Suppl. s2, 1995, pp. S46-S65. http://dx.doi.org/10.1111/j.1528-1157.1995.tb05999.x
[4]	G. L. Holmes, “Critical Issues in the Treatment of Epilepsy,” American Journal of Hospital Pharmacist, Vol. 50, Suppl. 5, 1993, pp. S5-S16.
[5]	R. H. Mattson, “Efficacy and Adverse Effects of Established and New Antiepileptic Drugs,” Epilepsia, Vol. 36, Suppl. S2, 1995, S13-S26. http://dx.doi.org/10.1111/j.1528-1157.1995.tb05995.x
[6]	E. B. Samren, C. M. V. Duijn, G. C. M. L. Christiaens, A. Hofman and D. Lindhout, “Antiepileptic Drug Regimens and Major Congenital Abnormalities in the Offspring,” Annals of Neurology, Vol. 46, No. 5, 2001, pp. 739-746. http://dx.doi.org/10.1002/1531-8249(199911)46:5<739::AID-ANA9>3.0.CO;2-2
[7]	M. C. Smith and T. P. Bleck, “Convulsive Disorders: Toxicity of Anticonvulsants,” Clinical Neuropharmacology, Vol. 14, No. 2, 1991, pp. 97-115. http://dx.doi.org/10.1097/00002826-199104000-00001
[8]	I. I. Ali, L. Schuh, G. L. Barkley and J. R. Gates, “Antiepileptic Drugs and Reduced Bone Mineral Density,” Epilepsy & Behavior, Vol. 5, No. 3, 2004, pp. 296-300. http://dx.doi.org/10.1016/j.yebeh.2004.02.005
[9]	D. Heaney, “The Pharmacoeconomics of the New Antiepileptic Drugs,” Epilepsia, Vol. 40, Suppl. s8, 1999, pp. 25-31. http://dx.doi.org/10.1111/j.1528-1157.1999.tb00944.x
[10]	Z. Razi, “Al-Hawi-Fil-Tib (Urdu Translation),” CCRUM Publication, New Delhi, 1997.
[11]	I. Baitar, “Al-Jam-e-ul-Mufradat-Al-Adviah-Wal-Aghziya (Urdu translation),” CCRUM publication, New Delhi, 1999.
[12]	N. G. Khan, “Khazainul Adviah,” Matba Munshi Naval Kishore, Lucknow, 1921.
[13]	D. Bendjeddou, K. Lalaoui and D. Satta, “Immunostimulating Activity of the Hot Water-Soluble Polysaccharide Extracts of Anacyclus pyrethrum, Alpinia galanga and Citrullus colocynthis,” Journal of Ethnopharmacology, Vol. 88, No. 2-3, 2003, pp. 155-160. http://dx.doi.org/10.1016/S0378-8741(03)00226-5
[14]	V. Sharma, M. Thakur, N. S. Chauhan and V. K. Dixit, “Evaluation of the Anabolic, Aphrodisiac and Reproductive Activity of Anacyclus pyrethrum DC in Male Rats,” Scientia Pharmaceutica, Vol. 77, 2009, pp. 97-110. http://dx.doi.org/10.3797/scipharm.0808-14
[15]	J. M. Gulland and G. U. Hopton, “Pellitorine, the Pungent Principle of Anacyclus pyrethrum,” Journal of Chemical Society, 1930, pp. 6-11. http://dx.doi.org/10.1039/jr9300000006
[16]	R. S. Burden and L. Crombie, “Amides of Vegetable Origin. Part XII. A New Series of Alka-2, 4-Dienoic Tyramine-Amides from Anacyclus pyrethrum D. C. (Compositae),” Journal of the Chemical Society C: Organic, No. 19, 1969, pp. 2477-2481. http://dx.doi.org/10.1039/j39690002477
[17]	“The Wealth of India,” CSIR Publication, New Delhi, 1985.
[18]	K. Sukumaran and R. Kuttan, “Inhibition of Tobacco-Induced Mutagenesis by Eugenol and Plant Extracts,” Mutation Research/Genetic Toxicology, Vol. 343, No. 1, 1995, pp. 25-30. http://dx.doi.org/10.1016/0165-1218(95)90059-4
[19]	A. Gorji and M. K. Ghadiri, “History of Epilepsy in Medieval Iranian Medicine,” Neuroscience & Biobehavoiral Reviews, Vol. 25, No. 5, 2001, pp. 455-461. http://dx.doi.org/10.1016/S0149-7634(01)00025-2
[20]	D. Vohora, S. N. Pal and K. K. Pillai, “Thioperamide a Selective Histamine H3 Receptor Antagonist, Protects Against PTZ-Induced Seizures in Mice,” Life Science, Vol. 66, No. 22, 2000, pp. 297-301. http://dx.doi.org/10.1016/S0024-3205(00)00548-8
[21]	Y. Kitano, C. Usui, K. Takasuna, M. Hirohashi and M. Nomura, “Increasing-Current Electroshock Seizure Test: A New Method for Assessment of Antiand Pro-Convulsant Activities of Drugs in Mice,” Journal of Pharmacological and Toxicological Methods, Vol. 35, No. 1, 1996, pp. 25-29. http://dx.doi.org/10.1016/1056-8719(95)00115-8
[22]	A. Ali, F. J. Ahmad, K. K. Pillai and D. Vohora, “Evidence of the Antiepileptic Potential of Amiloride with Neuropharmacological Benefits in Rodent Models of Epilepsy and Behavior,” Epilepsy & Behaviour, Vol. 5, No. 3, 2004, pp. 322-328. http://dx.doi.org/10.1016/j.yebeh.2004.01.005
[23]	T. C. M. Lima, G. S. Morato and R. N. Takahashi, “Evaluation of the Control Properties of Artemisia Verloturum,” Planta Medica, Vol. 59, No. 4, 1993, pp. 326-329. http://dx.doi.org/10.1055/s-2006-959692
[24]	H. H. Frey and W. Loscher, “Di-n-Propyletic Acid-Profile of Anticonvulsant Activity in Mice,” Arzneimittelforschung, Vol. 26, 1976, pp. 299-301.
[25]	F. Baldino and H. M. Geller, “Sodium Valproate Enhancement of Gamma-Aminobutyric Acid (GABA) Inhibition: Electro-Physiological Evidence for Anticonvulsant Activity,” The Journal of Pharmacology and Experimental Therapeutics, Vol. 217, No. 2, 1981, pp. 445-450.
[26]	J. Szabadics and L. Erdelyi, “Pre-and Postsynaptic Effect of Eugenol and Related Compounds on Helix pomatia L. Neurons,” Acta Biologica Hungarica, Vol. 51, No. 2-4, 2000, pp. 265-273.
[27]	M. B. Wie, M. H. Won, K. H. Lee, J. H. Shin, J. C. Lee, H. W. Suh, D. K. Song and Y. H. Kim, “Eugenol Protects Neuronal Cells from Excitotoxic and Oxidative Injury in Primary Cortical Cultures,” Neuroscience Letters, Vol. 225, No. 4, 1997, pp. 93-96. http://dx.doi.org/10.1016/S0304-3940(97)00195-X
[28]	M. H. Won, J. C. Lee, Y. H. Kim, D. K. Song, H. W. Suh, Y. S. Oh, J. H. Kim, T. K. Shin, Y. J. Lee and M. B. Wie, “Post-Ischemic Hypothermia Induced by Eugenol Protects Hippocampal Neurons from Global Ischemia in Gerbils,” Neuroscience Letters, Vol. 254, No. 2, 1998, pp. 101-104. http://dx.doi.org/10.1016/S0304-3940(98)00664-8