Anticonvulsant, anxiolytic and hypnotic effects of <i>Monodora myristica</i> (Gaertn, Dunal.) dried seed essential oil in mice

Authors

  • Felix O. Afolabi Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, University of Medical Sciences, Ondo, Ondo State, Nigeria
  • Moses A. Akanmu Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
  • Christiana A. Elusiyan DrugResearch and Production Unit, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State. 
  • Idris A Oyemitan Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.

DOI:

https://doi.org/10.51412/psnnjp.2024.14

Keywords:

amphetamine, hypnotic, anxiety, seizure, Monodora myristica

Abstract

Background: The seed of Monodora myristica (Gaertn, Dunal.) has been reported to be useful in the management of neuralgia, headaches, rheumatism, pain, cough and tonic among others, however, the central nervous system effect of the essential oil has not been investigated. This study was carried out to evaluate the anticonvulsant, anxiolytic and hypnotic effects of M. myristica dried seed essential oil in mice.

Method: The essential oil of M. myristica (EMM) was obtained from the dried seeds by hydrodistillation, while the median lethal dose (LD ) was determined using Lorke's method. Doses of 50 EMM at 25, 50, 100 mg/kg, per oral were used for the novelty-induced behavior, anticonvulsant and hypnotic activities while lower doses of EMM at 6.25, 12.5, 25 mg/kg, per oral were used for the anxiolytic activities. The novelty-induced behaviours were determined in the open field test (OFT). The essential oil effect on amphetamine-induced hyperlocomotor response in the OFT was determined. The anticonvulsant effect was evaluated using chemoconvulsants such as pentylenetetrazole (PTZ) and strychnine (STR)–induced convulsion models. Potential anxiolytic effect was investigated using hole board (HB) and elevated plus maze (EPM) models. The hypnotic effect was determined using ketamine-induced sleep model where the sleep latency and the total sleeping time were assessed.

Results: Oral LD of EMM was 283 mg/kg and EMM in the open field test caused significant (p<0.01) 50 dose-dependent decrease in locomotion, rearing and grooming activities suggesting that EMM possessed central nervous system depressant activity. It significantly (p<0.05) inhibited amphetamineinduced hyperlocomotor behavio  therefore suggesting that EMM may be useful in alleviating disorder related to hyperactivity. Oral administration of EMM signifi ant (p<0.05) delayed the onset of seizures induced by PTZ and STR but did not protect against seizures. EMM also caused significant (p<0.05) reduction in sleep latency and prolongation of total sleep time suggesting that it has hypnotic effect. EMM did not show any significant anxiolytic effects in HB and EPM models.

Conclusion: The study showed that EMM possessed significant central inhibitory and hypnotic effects but has no anxiolytic properties. 

References

Veeresham C. Natural products derived from plants as a source of drugs. J Adv Pharm Technol Res. 2012 Oct;3(4):200-1. doi: 10.4103/2231-

104709..

Ekeanyanwu CR, Ogu IG, Nwachukwu UP. Biochemical characteristics of the African nutmeg, Monodora myristica. Agric J. 2010;5:303–308..

Agiriga A, Siwela M. Monodora myristica(Gaertn.) Dunal: Aplant with multiple food, health and medicinal applications: a review, Am. J. Food

Technol. 2017;12(4): 271-284.

Onyenibe NS, Fowokemi KT, Emmanuel OB. African Nutmeg (Monodora Myristica) Lowers Cholesterol and Modulates Lipid Peroxidation in

Experimentally Induced Hypercholesterolemic Male Wistar Rats. Int J Biomed Sci. 2015 Jun;11(2):86-92.

Iwu MM. Handbook of African Medicinal Plants. CRC Press, Boca Raton, FL, USA. 1993.

Odoh UE, Ezugwu CO, and Ajali IU. Antimicrobial activity of Monodora myristicaseed oil. J. Pharma. Allied Sci., 2004; 2: 233 – 236.

Silva MI, de Aquino Neto MR, Teixeira Neto PF, Moura BA, do Amaral JF, de Sousa DP, Vasconcelos SM, de Sousa FC. Central nervous

system activity of acute administration of isopulegol in mice. Pharmacol Biochem Behav. 2007 Dec; 88(2): 141 - 7. doi: 10.1016/j.pbb.2007.07.015. Epub 2007 Jul 27.

Nguefack J, Leth V, Amvam Zollo PH, Mathur SB. Evaluation of five essential oils from aromatic plants of Cameroon for controlling food spoilage and mycotoxin producing fungi. Int J Food Microbiol. 2004 Aug 1;94(3):329-34. doi: 10.1016/j.ijfoodmicro.2004.02.017.

National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington (DC): National Academies Press (US); 2011.

Castro CA, Hogan JB, Benson KA, Shehata CW, Landauer MR. Behavioral effects of vehicles: DMSO, ethanol, Tween-20, Tween-80, and

emulphor-620. Pharmacol Biochem Behav. 1995 Apr; 50(4): 521 - 6. doi: 10.1016/0091-3057(94)00331-9.

Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol. 1983 Dec;54(4):275-87. doi: 10.1007/BF01234480.

Ajayi AA, Ukponmwan OE. Possible evidence of angiotensin II and endogenous opioid modulation of novelty-induced rearing in the rat. Afr J Med Med Sci. 1994 Sep;23(3):287-90.

Oyekunle OA, Akanmu MA, Ogundeji TP. Evaluation of anxiolytic and novelty induced behaviours following bee-honey consumption in

rats. J Neurosci Behav Health. 2010;2:38–43.

Lan A, Einat H. Questioning the predictive validity of the amphetamine-induced hyperactivity model for screening mood stabilizing drugs. Behav Brain Res. 2019 Apr 19;362:109-113. doi: 10.1016/j.bbr.2019.01.006. Epub 2019 Jan 7.

Löscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic

drugs. Seizure. 2011 Jun;20(5):359-68. doi: 10.1016/j.seizure.2011.01.003. Epub 2011 Feb 2.

Jahromi HK, Khorram A, Atashpour S, Jalali M, Kargar Jahromi Z, Mohammadi F, Serpoosh M.A, Sadeghi N. The Effect of Hydroalcoholic Extract

of Salep On Pentylenetetrazole-induced Seizure in Adult Male Rats. Iran J Neurosurg. 2023; 9:E1. http://dx.doi.org/10.32598/irjns.9.1

Amabeoku G.J., Kinyua C.G. Evaluation of the anticonvulsant activity of Zanthoxylum capense(Thunb.) Harv. (Rutaceae) in mice. Int. J.

Pharmacol. 2010;6:844–853.

Amabeoku G, Chandomba R. Strychnine-induced seizures in mice: the role of noradrenaline. Prog Neuropsychopharmacol Biol Psychiatry. 1994 Jul; 18(4): 753 - 63. doi: 10.1016/0278-5846(94)90082-5. PMID: 7938564.

Griebel G, Perrault G, Tan S, Schoemaker H, Sanger DJ. Pharmacological studies on synthetic flavonoids: comparison with diazepam.

Neuropharmacology. 1999 Jul;38(7):965-77. doi: 10.1016/s0028-3908(99)00026-x.

Goehler LE, Park SM, Opitz N, Lyte M, Gaykema RP. Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible

anatomical substrates for viscerosensory modulation of exploratory behavior. Brain Behav Immun. 2008 Mar; 22(3): 354 - 66. doi:

1016/j.bbi.2007.08.009. Epub 2007 Oct 24.

Takeda H, Tsuji M, Matsumiya T. Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in

mice. Eur J Pharmacol. 1998 May 29;350(1):21-9. doi: 10.1016/s0014-2999(98)00223-4.

Pellow S, Chopin P, File SE, Briley M. Validation of open:closed arm entries in an elevated plusmaze as a measure of anxiety in the rat. J eurosci Methods. 1985 Aug;14(3):149-67. doi: 10.1016/0165-0270(85)90031-7.

Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007;2(2):322-8. doi:

1038/nprot.2007.44.

Trullas R, Skolnick P. Differences in fear motivated behavior among inbred mouse strain. Psychopharmacology, 1993;111:323-331.

McGirr A, Berlim MT, Bond DJ, Fleck MP, Yatham LN, Lam RW. A systematic review and meta-analysis of randomized, double-blind,

placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med. 2015 Mar; 45(4): 693 - 704. doi: 10.1017/S0033291714001603. Epub 2014 Jul 10.

Ardalan M, Rafati AH, Nyengaard JR, Wegener G. Rapid antidepressant effect of ketamine correlates with astroglial plasticity in the

hippo campus. Br J Ph a rma c o l. 2 0 1 7 Mar;174(6):483-492. doi: 10.1111/bph.13714. Epub 2017 Feb 8.

Lv Y, Dai W, Ge A, Fan Y, Hu G, Zeng Y.Aquaporin-4 knockout mice exhibit increased hypnotic susceptibility to ketamine. Brain Behav.

;8:e00990. https://doi.org/10.1002/brb3.990

Zlomuzica, A., Viggiano, D., De Souza Silva, M. A., Ishizuka, T., Carnevale, U. A. G., Ruocco, L. A., Watanabe, T., Sadile, A. G., Huston, J. P., &

Dere, E. The histamine H1-receptor mediates the motivational effects of novelty. Eur J Neurosci, 2008: 27(6), 1461 – 1474. https://doi.org/10.1111/j.1460-9568.2008.06115.x

Zlomuzica, A., Viggiano, D., De Souza Silva, M. A., Ishizuka, T., Carnevale, U. G., Rangel-Gomez M, Meeter M. Neurotransmitters and Novelty: A

Systematic Review. J Psychopharmacol. 2016 Jan;30(1):3-12. doi: 10.1177/0269881115612238. Epub 2015 Nov 24.

Wöhr M. Measuring mania-like elevated mood through amphetamine-induced 50-kHz ultrasonic vocalizations in rats. Br J Pharmacol. 2022

Sep;179(17):4201-4219. doi: 10.1111/bph.15487. Epub 2021 May 21.

Sharma AN, Fries GR, Galvez JF, Valvassori SS, Soares JC, Carvalho AF, Quevedo J. Modeling mania in preclinical settings: A comprehensive

review. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Apr 3;66:22-34. doi: 10.1016/j.pnpbp.2015.11.001. Epub 2015 Nov 4.

Cain ME, Mersmann MG, Gill MJ, Pittenger ST. Dose-dependent effects of differential rearing on amphetamine-induced hyperactivity. Behav

Pharmacol. 2012 Dec;23(8):744-53. doi: 10.1097/FBP.0b013e32835a38ec.

Heal DJ, Smith SL, Gosden J, Nutt DJ.Amphetamine, past and present- - a pharmacological and clinical perspective. J

Psychopharmacol. 2013 Jun;27(6):479-96. doi: 10.1177/0269881113482532. Epub 2013 Mar 28.

Mejias, R., Rodriguez-Gotor, J.J., Niwa, M. et al.Increased novelty-induced locomotion, sensitivity to amphetamine, and extracellular

dopamine in striatum of Zdhhc15-deficient mice. Transl Psychiatry 11, 65(2021) . https://doi.org/10.1038/s41398-020-01194-6

Lan A, Einat H. Questioning the predictive validity of the amphetamine-induced hyperactivity model for screening mood stabilizing drugs. Behav Brain Res. 2019 Apr 19;362:109-113. doi: 10.1016/j.bbr.2019.01.006. Epub 2019 Jan 7. PMID: 30630015.

Alachkar A, Ojha SK, Sadeq A, Adem A, Frank A, Stark H, Sadek B. Experimental Models for the Discovery of Novel Anticonvulsant Drugs: Focus

on Pentylenetetrazole-Induced Seizures and Associated Memory Deficits. Curr Pharm Des. 2020; 26(15): 1693-1711. doi :

2174/1381612826666200131105324.

Huang RQ, Bell-Horner CL, Dibas MI, Covey DF, Drewe JA, Dillon GH. Pentylenetetrazoleinduced inhibition of recombinant amma-aminobutyric acid type A (GABA(A)) receptors: mechanism and site of action. J Pharmacol Exp

Ther. 2001 Sep;298(3):986-95.

Swinyard EA, Woodhead JH, White HS, Franklin MR. Experimental selection, quantification and evaluation of anticonvulsants. In: Levy R, Mattson R, Meldrum BS, Penry JK, Dreifuss FE. (Eds), Antiepileptic Drugs, 3rd ed., Raven Press New York. pp 85-102, 1989.

Kendall DA, Fox DA, Enna SJ. Effect of gammavinyl GABA on bicuculline-induced seizures. Neuropharmacology. 1981 Apr;20(4):351-5. doi:

1016/0028-3908(81)90008-3.

Patocka J. Chapter 16 - Strychnine, Editor(s): Ramesh C. Gupta, Handbook of Toxicology of Chemical Warfare Agents (Third Edition), Academic Press, ,Pages 239-247, 2020.

Takeda H, Tsuji M, Matsumiya T. Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol. 1998 May 29;350(1):21-9. doi: 10.1016/s0014-2999(98)00223-4.

Dawson, G. R. and M. D. Tricklebank, 1995. Use of the elevated plus maze in the search for novel anxiolytic agents. Trends Pharmacol. Sci., 16:33-36.

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Published

2024-04-30

How to Cite

Afolabi, F. O., Akanmu, M. A., Elusiyan, C. A., & Oyemitan, I. A. (2024). Anticonvulsant, anxiolytic and hypnotic effects of <i>Monodora myristica</i> (Gaertn, Dunal.) dried seed essential oil in mice. The Nigerian Journal of Pharmacy, 58(1), 134–148. https://doi.org/10.51412/psnnjp.2024.14