Paeoniflorin Farede Maksimal Elektroşok ve PTZ Nöbetlerini Azaltır

Yıl 2012, Sayı: 1, 17 - 30, 01.01.2012

Semra Koyunoğlu Okan Arıhan Yıldırım Sara Rüştü Onur Sedef Kır İhsan Çalış

Öz

Paeonia türleri halk tıbbında epilepsinin tedavisi amacıyla kullanılan türlerdir, ancak Paeonia türlerinin ana etken maddesi olan paeoniflorinin etkileri bilimsel olarak incelenmemiştir. Bu çalışmada paeoniflorinin Maksimal Elektroşok MES ve pentilentetrazol PTZ ile oluşurulan jeneralize tonik-klonik konvülsiyon modelindeki etkileri araştırılmıştır. MES testinde paeoniflorin 100, 250 ve 500 mg/kg dozlarında intraperitoneal yolla verilmiştir. MES eşik testi ile hayvanların yüzde ellisinde konvülsiyona neden olan akım ölçülmüştür. Paeoniflorinin konvülsiyonlar üzerine etkileri once MES testi ile değerlendirilmiştir. Paeoniflorin 250 ve 500 mg/kg dozlarında antikonvülsif etki göstermiş ve konvülsiyona giren hayvan sayısını azaltmıştır. Paeoniflorinin antikonvülsif etkileri enjeksiyondan 90 dakika sonra gözlenmiştir. PTZ testinde paeoniflorinin 100 ve 250 mg/kg dozlarında jeneralize konvülsiyonlar için gereken süreyi ve konvülsiyon süresini doza bağımlı olarak uzatmıştır. Bu bulgular ışığında, paeoniflorinin MES’le indüklenen jeneralize tonik-klonik konvülsiyonları inhibe ettiğini değerlendirdik. Paeoniflorin ve paeonia türlerinde bulunan diğer monoterpenik glikozitler yeni antikonvülsif ilaçların geliştirilmesi için aday olarak değerlendirilebilir.

Anahtar Kelimeler

Şakayık, Paeonia, paeoniflorin, maksimal elektroşok, PTZ, antikonvülsif

Paeoniflorin Diminishes Maximal Electroshock - and PTZ - induced Convulsions in Mice

Öz

Paeonia species have been used to treat epilepsia in traditional medicine, however the effects of paeoniflorin, the main constituent of Paeonia species have not been studied scientifically. We studied the effects of paeoniflorin with generalized tonic-clonic convulsion model induced by Maximal Electroshock MES and pentylenetetrazolium PTZ in mice. In MES test paeoniflorin was given intraperitoneally at doses of 100, 250 and 500 mg/kg. The current strength which yielded convulsions in 50 % of the animals was calculated by MES threshold test. The effects of paeoniflorin on convulsions were evaluated firstly via MES test. Paeoniflorin exerted anticonvulsive effect at 250 and 500 mg/kg and decreased the number of animals having convulsion. Anticonvulsive effect of paeoniflorin was observed 90 min after injection. In PTZ test we observed that 100 and 250 mg/kg paeoniflorin prolongs both the time period required for generalized convulsions and the duration in a dose dependent fashion. Based on these findings, we conclude that paeoniflorin inhibited generalized tonic-clonic convulsions induced by MES, and partially attenuated seizures in absence seizure model. Paeoniflorin and other monoterpenic glycosides of Paeonia species may be considered as a candidate for the development of a new anticonvulsive drug.

Anahtar Kelimeler

Paeony, Paeonia, paeoniflorin, maximal electroshock, PTZ, antiseizure

Kaynakça

• Ai M., Yamaguchi, T., Odaka, T., Mitsuhashi, K., Shishido, T., Yan, J., Seza, A., Saisho, H. : Objective assessment of the antispasmodic effect of shakuyaku-kanzo-to (TJ-68), a Chinese herbal medicine, on the colonic wall by direct spraying during colonoscopy, World J Gastroenterol, 12, 760-764 (2006)
• Eadie, M.J. : The antiepileptic Materia Medica of Pediacus Dioscorides, J Clin Neurosci 11 (2004) 697-701
• Kaneda, M., Iitaka, Y., Shibata, S. : Chemical studies on the oriental plant drugs - XXXII. The absolute structures of paeoniflorin, albiflorin, oxypaeoniflorin and benzoyl- paeoniflorin isolated from Chinese paeony root, Tetrahedron, 28, 4309-4317 (1972)
• Wen, R.X., Li, W., Li, Y., Cui, C.D., Yin, X.J., Liao, F.L. : Recent pharmacological study on sanshengwan decoction, Zhongguo Zhong Yao Za Zhi, 30, 923-925 (2005)
• Hijikata, Y., Yasuhara, A., Yoshida, Y., Sento, S. : Traditional chinese medicine treat- ment of epilepsy, J Altern Complement Med, 12, 673-677 (2006)
• Pollard, J. R., French, J. : Antiepileptic drugs in development, Lancet Neurol, 5, 1064- 1067 (2006)
• Hardman, J.G., Limbird, L.E., Gilman, A.G.: In Goodman & Gilman’s The Pharmaco- logical Basis of Therapeutics. McGraw-Hill: New York (2001) 945
• Sunaga, K. , Sugaya, E., Kajiwara, K., Tsuda, T., Sugaya, A., Kimura, M. : Molecular mechanism of preventive effect of peony root extract on neuron damage, J Herb Phar- macother, 4, 9-20 (2004)
• Tsuda, T., Sugaya, A., Ohguchi, H., Kishida, N., Sugaya, E. : Protective effects of peony root extract and its components on neuron damage in the hippocampus induced by the cobalt focus epilepsy model, Exp Neurol, 146, 518-525 (1997)
• Sugaya, A., Suzuki, T., Sugaya, E., Yuyama, N., Yasuda, K., Tsuda, T. : Inhibitory effect of peony root extract on pentylenetetrazol-induced EEG power spectrum changes and extracellular calcium concentration changes in rat cerebral cortex, J Ethnopharmacol, 33, 159-167 (1991)
• Tsai, T.Y., Wu, S.N., Liu, Y.C., Wu, A.Z., Tsai, Y.C. : Inhibitory action of L-type Ca2+ current by paeoniflorin, a major constituent of peony root, in NG108-15 neuronal cells, Eur J Pharmacol, 523, 16-24 (2005)
• Sugaya, E., Jin, W., Sugaya, A., Sunaga, K., Tsuda, T. : Inhibitory effects of peony root extract on the large conductance calcium-activated potassium current essential in pro- duction of bursting activity, J Herb Pharmacother, 6, 65-77 (2006)
• Dong, X.P., Xu, T.L. : Radix paeoniae rubra suppression of sodium current in acutely dissociated rat hippocampal CA1 neurons, Brain Res, 940, 1-9 (2002)
• Zhang, G.Q., Hao, X.M., Chen, S.Z., Zhou, P.A., Cheng, H.P., Wu, C.H. : Blockade of paeoniflorin on sodium current in mouse hippocampal CA1 neurons, Acta Pharmacol Sin, 24, 1248-1252 (2003)
• Swinyard, E.A., Woodhead, J.H., White, H.S., Franklin, M.R.: Experimental selection, quantification, and evaluation of anticonvulsivants. In: Antiepileptic Drugs: Levy R, Wattson R, Meldrum B, Penry JK, Dreifuss FE (ed). Raven Press: New York, (1989) 85–101
• Löscher, W., Schmidt, D. : Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations, Epi- lepsy Res, 2, 145–181 (1988)
• Shibata, S., Nakahara, M. : Studies on the constituents of Japanese and Chinese crude drugs. VIII. Paeoniflorin, a glucoside on Chinese paeony root. (1), Chem. Pharm. Bull, 11, 372-378 (1963)
• Luszczki, J.J., Mohamed, M., Czuczwar, S.J. : 2-phosphonomethyl-pentanedioic acid (glutamate carboxypeptidase II inhibitor) increases threshold for electroconvulsions and enhances the antiseizure action of valproate against maximal electroshock-in- duced seizures in mice, Eur J Pharmacol, 531, 66-73 (2006)
• Litchfield, J.T. Jr, Wilcoxon, F. : A simplified method of evaluating dose-effect experi- ments, J Pharmacol Exp Ther, 96, 99-113 (1949)
• Luszczki, J.J., Czuczwar, S.J. : Interaction between lamotrigine and felbamate in the maximal electroshock-induced seizures in mice: an isobolographic analysis, Eur Neu- ropsychopharmacol, 15, 133-142 (2005)
• Buchthal, F., Svensmark, O. : Aspects of the pharmacology of phenytoin (dilantin) and phenobarbital relevant to their dosage in the treatment of epilepsy, Epilepsia, 1, 373- 384 (1960)
• Johnson, S.W., Riker, W.K. : Dose-response analysis of phenytoin on electrically in- duced seizures and spontaneous activity of cerebellar purkinje cells in the frog, Epilep- sia, 23, 123-131 (1982)
• McLean, M.J., MacDonald, R.L. : Cabamazepine and 10,11-epoxycarbamazepine pro- duce use-and voltage-dependent limitation of rapidly firing action potentials of mouse central neurons in cell culture. J Pharmacol Exp Ther. 238, 727-38 (1986)
• Krall, R.L., Penry, J.K., White, B.G., Kupferberg, H.J., Swinyard, E.A. : Antiepileptic drug development: II. Anticonvulsant drug screening. Epilepsia, 19:409–28 (1978)
• Dill, W.A., Kazenko, A., Wolf, L.M., Glazko, A.J.J. : Studies on 5±5k-diphenylhydantoin (Dilantin) in animals and man. J Pharmacol Exp Ther 1956; 118: 270±279.)
• Sahua, S., Duttaa G., Mandala, N., Goswamia, A.R., Ghosha. T. : Anticonvulsant effect of Marsilea quadrifolia Linn. on pentylenetetrazole induced seizure: A behavioral and EEG study in rats. J Ethnopharmacol 141, 537-51 (2012)
• Privitera, M.D. : Clinical rules for phenytoin dosing. Ann Pharmacother, 10, 1169-73 (1993).
• Betts, T., Betts, H. : John Hall and his epileptic patients--epilepsy management in early th century England. Seizure. 5, 411-4 (1998).
• Pedersena, M.E, Vestergaard, H.T., Hansen, S.L., Bah, S., Diallo, D., Jägera, A.K. : Pharmacological screening of Malian medicinal plants used against epilepsy and con- vulsions. J Ethnopharmacol, 121, 472-5 (2009)
• Kabuto, H., Yokoi, I., Mori, A. : Monoamine metabolites, iron induced seizures, and the anticonvulsant effect of tannins, Neurochem Res, 17, 585-590 (1992)
• Abdel-Hafez, A.A., Meselhy, M.R., Nakamura, N., Hattori, M., Watanabe, H., Mohamed, T.A., Mahfouz, N.M., El-Gendy, M.A. : Potent anticonvulsant paeonimetabolin-I deriva- tives obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis, Chem Pharm Bull, (Tokyo) 46, 1486-1487 (1998)
• Abdel-Hafez, A.A., Meselhy, M.R., Nakamura, N., Hattori, M., Watanabe, H., Murakami, Y., El-Gendy, M.A., Mahfouz, N.M., Mohamed, T.A. : Anticonvulsant activity of pae- onimetabolin-I adducts obtained by incubation of paeoniflorin and thiol compounds with Lactobacillus brevis, Biol Pharm Bull, 22, 491-497 (1999)