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Anticonvulsant activity of fraction isolated from ethanolic extract of heartwood of Cedrus deodara

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Abstract

The heartwood of Cedrus deodara is traditionally used for the treatment of neurological disorders in India. In this study, the compound 3,4-bis(3,4-dimethoxyphenyl)furan-2,5-dione (BDFD) isolated from the ethanolic extract of C. deodara was evaluated for its anticonvulsant activity. The experimental studies were carried out in albino mice (18–22 g) and rats (180–220 g), employing different models of convulsions. The N-methyl-d-aspartic acid (NMDA)-induced lethality test and estimation of brain gamma-aminobutyric acid (GABA) were carried out to investigate the mechanism of action of this compound. BDFD gave dose-dependent protection against pentylenetetrazole (PTZ)-, pilocarpine- and 6-Hz-induced convulsions but it could not inhibit NMDA-induced lethality. Motor incoordination was displayed when the BDFD dose exceeded 400 mg/kg, whereas the therapeutic dose was below 100 mg/kg in the PTZ, pilocarpine and 6-Hz models (39–90 mg/kg). Furthermore, brain GABA estimation revealed that this compound increases the GABA level. BDFD dose levels up to 150 mg/kg did not prevent NMDA-induced lethality, which proves its weak influence on the excitatory neurotransmitter glutamate. The findings of the experiments on various animal models clearly demonstrated that BDFD possesses anticonvulsant activity by enhancing inhibitory GABAminergic neurotransmission.

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References

  1. Kuruvilla A (1999) The burden and pharmacoeconomics of epilepsy in India. Seizure 8:436–437

    Article  CAS  PubMed  Google Scholar 

  2. Mattson RH (1995) Efficacy and adverse effects of established and new antiepileptic drugs. Epilepsia 36:S13–S26

    Article  CAS  PubMed  Google Scholar 

  3. Richard AH, Pamela CC (2009) Anticonvulsant drugs. In: Richard F, Luigi XC, Michelle AC (eds) Lippincott’s illustrated reviews pharmacology. Wolters Kluwer, New Delhi, p 175

    Google Scholar 

  4. Kirtikar KR, Basu BD (1999) Coniferae. In: Blatter E, Caius JF, Mhaskar KS (eds) Indian medicinal plants. International Book Distributors, India, pp 2390–2392

  5. Kar K, Puri VN, Patnaik GK, Sur RN, Dhawan BN, Kulshreshtra DK, Rastogi RP (1975) Spasmolytic constituents of Cedrus deodara Roxb Loud: pharmacological evaluation of himachalol. J Pharm Sci 64:258–262

    Article  CAS  PubMed  Google Scholar 

  6. Singh D, Aggarwal SK (1988) Insecticidal principles of himalayan cedar wood oils. J Chem Ecol 14:1145–1151

    Article  CAS  PubMed  Google Scholar 

  7. Nisha M, Kalyanasundaram M, Paily KP, Abidha P, Vanamail P, Balaraman K (2007) In vitro screening of medicinal plant extracts for macrofilaricidal activity. Parasitol Res 100:575–579

    Article  PubMed  Google Scholar 

  8. Pandey S, Devmurari V, Goyani M, Vaghani S, Jaganathan K (2009) Formulation and evaluation of Cedrus deodara Loud extract. Int J Chem Tech Res 100:1145–1152

    Google Scholar 

  9. Phillipson JD, Anderson LA (1989) Ethnopharmacology and western medicine. J Ethnopharmacol 25:61–72

    Article  CAS  PubMed  Google Scholar 

  10. Gautam R, Saklani A, Jachak SM (2007) Indian medicinal plants as a source of antimycobacterial agents. J Ethnopharmacol 110:200–234

    Article  CAS  PubMed  Google Scholar 

  11. Tiwari AK, Srinivas PV, Kumar SP, Rao JN (2001) Free radical scavenging active components from Cedrus deodara. J Agric Food Chem 49:4642–4645

    Article  CAS  PubMed  Google Scholar 

  12. Bisht LSB, Brindavanam NB, Kimothing P (1988) Comparative study of herbal agents used for fumigation in relation to formalin. Anc Sci Life 28:125–132

    Google Scholar 

  13. Ramesh C, Nandakumar K, Radhakrishnan R, Rangappa S, Murugananthan G, Sahil T (2010) Anti-urolithiatic activity of heart wood extract of Cedrus deodara in rats. J Complement Integr Med 7:1–9

    Google Scholar 

  14. Kumar A, Singh V, Chaudhary AK (2011) Gastric antisecretory and antiulcer activities of Cedrus deodara Roxb Loud in wistar rats. J Ethnopharmacol 134:294–297

    Article  PubMed  Google Scholar 

  15. Sachin BS, Koul M, Zutchi A, Singh SK, Tikoo AK, Tikoo MK, Saxena AK, Sharma SC, Johri RK (2008) Simultaneous high performance liquid chromatographic determination of Cedrus deodara active constituents and their pharmacokinetic profile in mice. J Chromatogr B 862:237–241

    Article  CAS  Google Scholar 

  16. Dhayabaran D, Florance J, Nandakumar K, Puratchikody A (2012) Isolation and anxiolytic activity of 3,4-bis (3,4-dimethoxyphenyl) furan-2,5-dione from the ethanolic extract of heart wood of Cedrus deodara. Med Chem Res 21:3460–3464

    Article  CAS  Google Scholar 

  17. Kokate TG, Svensson BE, Rogawski MA (1994) Anticonvulsant activity of neurosteroids: correlation with γ-aminobutyric acid-evoked chloride current potentiation. J Pharm Exp Ther 270:1223–1228

    CAS  Google Scholar 

  18. Barton ME, Peters SC, Shannon HE (2003) Comparison of the effect of glutamate receptor modulators in the 6 Hz and maximal electroshock seizure models. Epilepsy Res 56:17–26

    Article  CAS  PubMed  Google Scholar 

  19. Kokate TG, Cohen AL, Karp E, Rogawski MA (1996) Neuroactive steroids protect against pilocarpine and kainic acid induced limbic seizures and status epilepticus in mice. Neuropharmacology 35:1049–1056

    Article  CAS  PubMed  Google Scholar 

  20. Yamaguchi S, Donevan SD, Rogawski MA (1993) Anticonvulsant activity of AMPA/kainate antagonists: comparison of GYKJ 52466 and NBQX in maximal electroshock and chemoconvulsant seizure models. Epilepsy Res 15:179–184

    Article  CAS  PubMed  Google Scholar 

  21. Maynert EW, Klingman GI, Kaji HK (1962) Tolerance to morphine. II. Lack of effects on brain 5-hydroxytryptamine and γ-aminobutyric acid. J Pharmacol Exp Ther 135:296–299

    CAS  PubMed  Google Scholar 

  22. Loscher W, Schmidt D (1988) Which animal model should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res 2:145–181

    Article  CAS  PubMed  Google Scholar 

  23. Goyal M, Nagori BP, Sasmal D (2009) Sedative and anticonvulsant effects of an alcoholic extract of Capparis deciduas. J Nat Med 63:375–379

    Article  PubMed  Google Scholar 

  24. Swinyard EA (1972) Electrically induced convulsions. In: Purpura DP, Penry JK, Tower DB, Woodbury DM, Walter RD (eds) Experimental models of epilepsy––a manual for the laboratory worker. Raven Press, New York, pp 433–458

    Google Scholar 

  25. Porter RJ, Cereghino JJ, Gladding GD, Hessie BJ, Kupferberg HJ (1984) Antiepileptic drug development program. Cleve Clin Q 51:293–305

    Article  CAS  PubMed  Google Scholar 

  26. William JG (2001) Acute seizure tests in epilepsy research: electroshock and chemical induced convulsions in the mouse. Curr Protoc Pharmacol 5.22.1–5.22.22

  27. Turski L, Ikonomidou C, Turski WA, Bortolotto ZA, Cavalheiro EA (1989) Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: A novel experimental model of intractable epilepsy. Synapse 3:154–171

    Article  CAS  PubMed  Google Scholar 

  28. Leander JD, Lawson RR, Ornstein PL, Zimmerman DM (1988) N-methyl-d-aspartic acid induced lethality in mice: selective antagonism by phencyclidine-like drugs. Brain Res 448:115–120

    Article  CAS  PubMed  Google Scholar 

  29. Jean LM, Lorenzo P, Bernadette P (1989) Convulsions induced by centrally administered NMDA in mice: effect of NMDA antagonists, benzodiazepines, minor tranquilizers and anticonvulsants. Br J Pharmacol 98:1050–1054

    Article  Google Scholar 

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Acknowledgments

One of the authors (Daniel Dhayabaran) is grateful to Farooqia College of Pharmacy, Mysore, Karnataka, India for providing facilities and support for the successful completion of this research work. The authors are also grateful to Dr. Gopalan Kutty, Professor, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India for his services in language editing.

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Correspondence to Ayarivan Puratchikody.

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Dhayabaran, D., Florance, E.J., Nandakumar, K. et al. Anticonvulsant activity of fraction isolated from ethanolic extract of heartwood of Cedrus deodara . J Nat Med 68, 310–315 (2014). https://doi.org/10.1007/s11418-013-0798-4

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