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Anticonvulsant activity of methanolic extract of Withania cogulans in mice

Abstract

Mental and neurological diseases including depression, Parkinson’s disease, dementia, epilepsy, anxiety disorders and bipolar disorders account for a considerable amount of the world’s disease burden. Unfortunately, drugs used in the treatment of neurological diseases are expensive, symptomatic and they produce undesirable side effects. People from different cultures prefer to use medicinal plants for the treatment of various ailments ranging from plain to perplex disorders because they are most affordable, cost effective and easily accessible source of treatment in the primary healthcare system throughout the world. Withania coagulans, an erect grayish under-shrub belongs to family Solanaceae. It is common in Pakistan, East India, Iran and Afghanistan. The objective of this study was to analyze the anti-seizure activity of crude methanolic extract of Withania coagulans fruits (MeWc). For screening of this activity, maximal electroshock seizures model (MES) and chemically-induced seizures models were used. In maximal electroshock seizures test MeWc showed significant dose dependent percent protection against hind-limb tonic extension; significant and dose-dependent increase in latency to myoclonic jerks and tonic clonic convulsions and decrease in seizures duration were observed in PTZ-induced seizures. In strychnine-induced convulsions MeWc significantly increased latency to hind-limb tonic extension and percent protection from death in a dose-dependent manner. Thus, it was inferred from the experiments that extract of Withania coagulans showed anticonvulsant activity.

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References

  1. Ali A, Maher S, Khan SA, Chaudhary MI, Musharraf SG (2015) Sensitive quantification of six steroidal lactones in Withania coagulans extract by UHPLC electrospray tandem mass spectrometry. Steroids 104:176–181

    CAS  Article  Google Scholar 

  2. Coughenour LJ, McLean, Parker R (1977) A new device for the rapid measurement of impaired motor function in mice. Pharmacol Biochem Behav 6(3):351–353

    CAS  Article  Google Scholar 

  3. Fisher RS, Blume W, Elger C et al (2005) Epileptic seizures and epilepsy: definitions proposed by the international league against epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 46(4):470–472

    Article  Google Scholar 

  4. Goldenberg MM (2010) Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment. Pharm Therap 35(7):392

    Google Scholar 

  5. Huang RQ, Bell-Horner CL, Dibas MI, Covey DF, Drewe JA, Dillon GH (2001) Pentylenetetrazole-induced inhibition of recombinant gamma-aminobutyric acid type a (GABA(a)) receptors: mechanism and site of action. J Pharmacol Exp Ther 298(3):986–995

    CAS  PubMed  Google Scholar 

  6. Ihsan-ul-Haq, Youn UJ, Chai X, Park EJ, Kondratyuk TP, Simmons CJ, Borris RP, Mirza B, Pezzuto JM, Chang LC (2013) Biologically active withanolides from Withania coagulans. J Nat Prod 76(1):22–28

    CAS  Article  Google Scholar 

  7. Kapoor L (2000) Handbook of Ayurvedic medicinal plants: herbal reference library, vol 2. CRC press, Boca Raton

    Google Scholar 

  8. Kirtikar KR, Basu BD (1918) Indian medicinal plants, Part II. Apurva Krishna Bose, The Indian Press, Allahabad, pp 906–908

  9. Krall R, Penry JK, White BG et al (1978) Antiepileptic drug development:II. Anticonvulsant drug screening. Epilepsia 19(4):409–428. https://doi.org/10.1111/j.1528-1157.1978.tb04507.x

    CAS  Article  PubMed  Google Scholar 

  10. Kupferberg H (2001) Animal models used in the screening of antiepileptic drugs. Epilepsia 42(4):7–12

    Article  Google Scholar 

  11. Löscher W (2017) Animal models of seizures and epilepsy: past, present, and future role for the discovery of Antiseizure drugs. Neurochem Res 42(7):1873–1888

    Article  Google Scholar 

  12. Mac TL, Trans DS, Quet F et al (2007) Epidemiology, aetiology, and clinical management of epilepsy in Asia: a systematic review. Lancet Neurol 6(6):533–543. https://doi.org/10.1016/s1474-4422(07)70127-8

    Article  PubMed  Google Scholar 

  13. Maurya R (2010) Chemistry and pharmacology of Withania coagulans: an Ayurvedic remedy. J Pharm Pharmacol 62(2):153–160. https://doi.org/10.1211/jpp.62.02.0001

    CAS  Article  PubMed  Google Scholar 

  14. McGaraughty S, Henry JL (1998) The effects of strychnine, bicuculline, and ketamine onimmersion-inhibited'dorsal horn convergent neurons in intact and spinalized rats. Brain Res 784(1):63–70. https://doi.org/10.1016/s0006-8993(97)01153-0

    CAS  Article  PubMed  Google Scholar 

  15. Megiddo I, Colson A, Chisholm B et al (2016) Health and economic benefits of public financing of epilepsy treatment in India: an agent-based simulation model. Epilepsia 57(3):464–474. https://doi.org/10.1111/epi.13294

    Article  PubMed  PubMed Central  Google Scholar 

  16. Muhasaparur Ganesan R, Settu DK, Murkunde Y, Duraipandian C (2021) Pharmacological and pharmacokinetic effect of a polyherbal combination with Withania somnifera (L.) Dunal for the management of anxiety. J Ethnopharmacol 265:113337. https://doi.org/10.1016/j.jep.2020.113337

    CAS  Article  PubMed  Google Scholar 

  17. Prasad SK, Singh PN, Wahi AK, Hemalatha S (2010) Pharmacognostical standardization of Withania coagulans Dunal. Phcog J 2(11):386e–394e

    Article  Google Scholar 

  18. Shorvon S (1990) Epidemiology, classification, natural history, and genetics of epilepsy. Lancet 336(8707):93–96. https://doi.org/10.1016/0140-6736(90)91603-8

    CAS  Article  PubMed  Google Scholar 

  19. Soman S, Korah PK, Jayanarayanan S, Mathew J, Paulose CS (2012) Oxidative stress induced NMDA receptor alteration leads to spatial memory deficits in temporal lobe epilepsy: ameliorative effects of Withania somnifera and Withanolide a. Neurochem Res 37(9):1915–1927

    CAS  Article  Google Scholar 

  20. Soman S, Anju TR, Jayanarayanan S, Antony S, Paulose CS (2013) Impaired motor learning attributed to altered AMPA receptor function in the cerebellum of rats with temporal lobe epilepsy: ameliorating effects of Withania somnifera and withanolide a. Epilepsy Behav 27(3):484–491

    Article  Google Scholar 

  21. Stefan H, Wang Y, Pauli E, Schmidt B (2004) A new approach in anti-epileptic drug evaluation. Eur J Neurol 11(7):467–473. https://doi.org/10.1111/j.1468-1331.2004.00812.x

    CAS  Article  PubMed  Google Scholar 

  22. Thurman DJ, Ettore B, Charles EB et al (2011) Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia 52(s7):2–26. https://doi.org/10.1111/j.1528-1167.2011.03121.x

    CAS  Article  PubMed  Google Scholar 

  23. Trease GE, Evans WC (2009) Pharmacogonasy, 16th edn. Brown Publication, Charlestown

    Google Scholar 

  24. Vigil AL, Palou E, Alzamora SM (2005) Naturally occurring compounds—plant sources. Antimicrobials in food 28:429

    Google Scholar 

  25. Wojda E, Wlaz A, Patsalos PN, Luszczki J (2009) Isobolographic characterization of interactions of levetiracetam with the various antiepileptic drugs in the mouse 6Hz psychomotor seizure model. Epilepsy Res 86(2-3):163–174. https://doi.org/10.1016/j.eplepsyres.2009.06.003

    CAS  Article  PubMed  Google Scholar 

  26. Yemedje LP, Houinato D, Quet F, Druet-Cabanac M, Preux PM (2011) Understanding the differences in prevalence of epilepsy in tropical regions. J Epilepsia 52:1376–1381. https://doi.org/10.1016/s1474-4422(14)70114-0

    Article  Google Scholar 

  27. Zhu J, Park S, Jeong KH, Kim WJ (2020) Withanolide-a treatment exerts a neuroprotective effect via inhibiting neuroinflammation in the hippocampus after pilocarpine-induced status epilepticus. Epilepsy Res 165:106394

    CAS  Article  Google Scholar 

Download references

Acknowledgements

Authors are thankful to Dr. Syed Mujtaba Shah for identification of plant material and Dr. Mudassir Shah for critical comments on Manuscripts. This study has been financially supported National Research Program for University (NRPU # 3842) by Higher Education Commission of Pakistan.

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Authors

Contributions

ZFK, MAS and RUH designed the study. ZFK, BA and MJ performed experiments presented in this study. ZFK and AAA analyzed and interpreted the data and ZFK, MAS and RUH prepared manuscript.

Corresponding author

Correspondence to Rizwan ul Haq.

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Research involving animals

Study has been conducted on laboratory animals according to the approved ethical guidelines of the institution for care and use of laboratory animals with approval number AUST/Pharm/AEC/2016/008.

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All authors are willing to submit this manuscript in Metabolic Brain Disease.

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Data will be provided upon a reasonable request.

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Authors declare that they have not any scientific or financial conflict of interest to any person or organization. RUH received research grant from Higher Education Commission of Pakistan HEC/NRPU# 3842 and declare no conflict no interest.

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Khattak, Z.F., Ansari, B., Jamal, M. et al. Anticonvulsant activity of methanolic extract of Withania cogulans in mice. Metab Brain Dis 36, 2437–2443 (2021). https://doi.org/10.1007/s11011-021-00850-0

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Keywords

  • Withania coagulans
  • Anticonvulsant
  • Maximal electroshock seizure
  • PTZ-induced seizure
  • Epilepsy