فعالیت ضد تشنجی عصاره متانولی برگ Combretum hypopilinum Diels (Combretaceae) در حیوانات آزمایشگاهی

Subject Areas : Journal of Medicinal Herbs, "J. Med Herb" (Formerly known as Journal of Herbal Drugs or J. Herb Drug)

زکریا الحسن ¹ (بخش داروشناسی و درمانی ، دانشگاه احمدو بلو زاریا)
جامیلو یائو ² (بخش داروشناسی و درمانی ، دانشگاه احمدو بلو زاریا)
ایسا حسینی ³ (بخش فارماکولوژی ، دانشگاه میدوگوری ، نیجریه)

Received: 2021-01-22 Accepted : 2021-05-20 Published : 2021-07-01

Keywords: Picrotoxin, epilepsy, Pentylenetetrazole, Anticonvulsant, Combretum hypopilinum,

Abstract :

Background & Aim:The use of plants as medicine is an ancient practice common to all societies especially the African society and this practice continues to exist in developing nations. Combretum hypopilinum is harvested from the wild for local use of its gum, medicinal uses and timber, it is one of the eight most widely used plants for management of epilepsy in northern Nigeria. This study aimed at examining the anticonvulsant properties of methanol leaf extract of Combretum hypopilinum (MECH) in acute animal models as well as the possible mechanism involved in its anticonvulsant activities. . Experimental: The LD50 of the extract was calculated using OECD 423 starting with the limited dose of 5000mg/kg while the anticonvulsant activity of the extract was examined using maximal electroshock (MES), pentylenetetrazole (PTZ), strychnine and picrotoxin induced seizure models. For investigating the possible mechanism of the extract in PTZ model, flumazenil, naloxone, L-Argenin and sildenafil were administered to interact with the extract. Results: The LD50 of the extract was found to be greater than 2000mg/kg but less than 5000 mg/kg (oral). In maximal electroshock test, the extract protects only 30% of chicks against tonic hind limb extension (THLE) at the dose of 600 mg/kg. However, it significantly (p < 0.05) and dose dependently decreased the mean recovery time of the convulsed chicks. In PTZ model, the extract at the dose of 600mg/kg, protected mice by 66.66% and significantly (p < 0.005) delayed the mean onset of seizure. The extract significantly (p < 0.005) delayed the mean onset of seizure and increased the mean latency of mortality for unprotected mice in both strychnine and picrotoxin models. Flumazenil, naloxone, L-argenine and sildenafil reversed the anticonvulsant activity of MECH. Recommended applications/industries: The study suggested that MECH possessed bioactive component(s) responsible for its anticonvulsant effect, therefore, justify its use for the management of epilepsy amongst herbalists in Northern part of Nigeria.

References:

Adongo, D., Mante, P. and Woode, E. 2017. Anticonvulsant effect of antiaristoxicaria aqueous extract: Investigation using animal models of temporal lobe epilepsy. BMC Research Notes. 10(1) 22-33.

Ambavade, S.D., Mhetre, N.A., Muthal, A.P. and Bodhankar, S.L. 2009. Pharmacological evaluation of anticonvulsant activity of root extract of Saussurea lappa in mice. European Journal of Integrative Medicine, 1:131-137.

Burkill, H.M. 2000. The useful plants of west tropical Africa. Vol 15. Royal Botanical Garden Kew. UK.

Dhir, A., Naida, P.S. and Kulkarni, S.K. 2007. Neuroprotective effect of nimesulide, a preferencial COX-2 inhibitor against pentylenetetrazole PTZ-induced chemical parameters       in mice. African Journal of Biotechnology, 16: 691-697.

 

Hameed, U.R., Rehman, R., Ullah, T.A., Farhan, Z. M., Asad A.M., Tahir, I. and Salman K. 2015. Elemental analysis and evaluation of phytochemical and biological properties of Orbancheagyptica. Global Journal of Pharmacology, 9(1): 51-55.

Hosseini, M., Hamid R.S., Soodabeh, S., Hassan, A. and Ali, G. 2009. The effect of L-argenine and L-NAME on PTZ-induced seizures in Ovariectomized rats, an in vivo study. Seizure, 18:695-698.

Kasture, V.S., Kasture, S.B., Joshua, A.J., Damodaran, A. and Amit, A. 2002. Ootropic activity of BacoMind™, an enriched phytochemical composition from Bacopa            monnieri. Journal of Natural Remedies, 7: 166-173.

Krieger, R. 2001. Handbook of pesticide toxicology. 2nd Ed. Vol 1. Academic Press, San Diego, California. pp. 156

Kumar, S. and Singh, G. 2016. Pathophysiology of epilepsy: an updated review. International Journal of Medical and Health Research, 2(10): 32-36.

Muazu, J. and Kaita, A.H. 2008. A review of traditional plants used in the treatment of epilepsy amongst the Hausa/Fulani Tribes of Northern Nigeria. African Journal of Traditional Complementary and Alternative Medicines, 5(4): 387-390.

Nardone, R., Francesco, B. and Eugen, T. 2016. Acute symptomatic seizures caused by electrolyte disturbances. Journal of Clinical Neurology, 12(1): 21-33.

Nassiri-Asl, M. and Schwann, S. 2007. Anticonvulsant effect of Passiflora incarnate extract in mice: Involvement of benzodiazepines and opioid receptors. BMC Complementary and Alternative Medicine, 7:26.

Nejad, S.R., Motevalian, M., Fatemi, I. and Shojaii, A. 2017. Anticonvulsant effect of the hydroalcoholic extract of Alpinia officinarum rhizomes in mice: Involvement        of benzodiazepine and opioid receptors. Journal of Epilepsy Research, 7 (1): 33-38.

Nicoll, R.A. 2001. Introduction to the pharmacology of CNS drugs. In: Katzung, B.G. (Ed.), Basic and clinical pharmacology. 8th Ed. New York, Lange Medical Books/Mcgraw   Hill.

Nieoczym, D., Jarogniew, J.Ł., Stanisław, J.C. and Piotr, W. 2010. Effect of sildenafilon the anticonvulsant action of classical and second-generation antiepileptic drugs in maximal electroshock-induced seizures in mice. Epilepsia, 51(8):1552- 1559.

Ogunri, A.O. 2006. Epilepsy in Nigeria: A review of etiology, epidemiology and management. Benin Journal of Postgraduate Medicine, 8 (1): 27-51.

Okoh-Esene, R.U., Okogun, J.I., Okwute, S.K. and Thomas, S.A. 2013. An overview of the facts, myths and treatment of the disease condition known as “Epilepsy”. Journal  of Dental and Medical Sciences, 6(2): 7-19.

Panvan, K.K., Vidyasagar, G., Ramakrishna, D., Madhusudhana, I.R. and Gupta, A. 2011. Antiepileptic activity for methanolic extract of Vitexnegundo leaf against different animal models. Journal of Chemistry and Pharmaceutical Research, 3(4): 159-165.

Porter, R.J., Cereghino, J.J. and Gladding, G.D. 1984. Antiepileptic drug development program. Cleve Clinical, 51:293-305.

Preux, P.M. and Druet-Cabanac, M. 2005. Epidemiology and aetiology in sub-Saharan Africa. Lancet Neurol, 4(1): 21-31.

Ramin, A., Nafiseh, N. and Majid, J.S. 2015. Interaction between Naloxone and Tramdolin kindling model of seizure in rat. American Multidisciplinary International Research Journal, 2(4):13-17.

Rang, H.P, Dale, M.M., Ritter, J.M. and Moore, P.K. 2005. Rang and Dales Pharmacology, 5th Ed. Churchill Livingstone. India. Pp. 456-473.

Rashidian, A., Kazemi, F., Saeed, M., Ahmad, R.D., Shahram, E.M. and Seyed, M.R. 2017. Anticonvulsant effects of aerial parts of Verbena officinalis extract in mice: Involvement of benzodiazepine and opioid receptors. Journal of Evidence-Based     Complementary and Alternative Medicine, 22(4): 632-636.

Riazi, K., Roshanpour, M., Rafiei-Tabatabaei, N., Homayoun, H., Ebrahimi, F. and      Dehpour, A.R. 2006. The proconvulsant effect of Sildenafil in mice: Role of nitric oxide Cgmp pathway. British Journal of Pharmacology, 147: 935-943.

Sarma, P. and Bhattacharyya, A. 2014. Models of epilepsy used in antiepileptic drug discovery: A review. International Journal of Pharmacy and Pharmaceutical Sciences, 7-1; (11) 6.         

Sofowora, A. 1993. Medicinal plants and traditional medicine in Africa. 2nd Ed. Spectrum Books Ltd., Ibadan. Nigeria. pp. 289.

Swinyard, E.A., and Kupberg, H.J. 1985. Antiepileptic drugs: Detection, quantification and evaluation. Federation Proceedings, 44:39-43.

Swinyard, E.A., Woodhead, J.H., White, H.S. and Franklin, M.R. 1989. General principles: Experimental selection, quantification and evaluation of anticonvulsants. In: Levy, H., Mattson, R.H., Meldrum B., Penry, J.K. and Dreifuss, F.E. (Eds.): Antiepileptic Drugs, 3ed Ed, New York, Raven Press, pp. 85- 102.

Yemitan, K.O. and Adeyemi, O.O. 2013. Antiepileptogenic and anticonvulsant actions of Dalbergia saxatilis (Hook, F.) in sub-toxic chemical kindling and toxic convulsant models. European Journal of Medicinal Plants, 3(2): 288-296.

Uthayathas, S., Karuppagounder, S.S., Thrash, B.M., Parameshwaran, K., Suppiramaniam, V. and Dhanasekaran, M. 2007. Versatile effects of sildenafil: recent pharmacological applications. Pharmacological Reports, 59:150–163.

Venkateshwarlu, E., Umasankar, K., Sharvanabhava, B.S. and Venkateshwar, R.J. 2013. Screening of the anticonvulsant activity of some isatin derivatives in experimental seizure model and its effect on brain GABA levels in mice. American Journal of Pharmaceutical Science, (3)1; 42-46.  

Ya’u, J., Yaro, A.H., Musa, A.M., Abubakar, A., Yahaya, S.M., Chindo, B.A., Anuka, J.A. and Hussaini, I.M. 2014. Mechanisms of anticonvulsant Action of residual aqueous fraction (RAF) of the ethanol root bark extract of Carissa edulis. Journal of Natural Sciences Research, 4(22): 1329-1338.

Ziyaurrahman, A.R. and Jayvadan, P. 2012. Anticonvulsant effect of Boswellia serrata by modulation of endogenous biomarkers. Der Pharmacia Lettre, 4(4): 1308-1326.