Appraising the Neurobehavioural Toxicity Potential of Aqueous Methanol Leaf Extract of Tapinanthus globiferus Growing on Azadirachta indica

Main Article Content

A. M. Umarudeen
M. G. Magaji

Abstract

The high prevalence and disease burden of anxiety disorders against the paucity and liabilities of existing anxiolytics indicates a need for the discovery of additional/new anti-anxiety agents. However, it is necessary to further screen these new/putative anxiolytic compounds/extracts to rule out the unwanted neurobehavioural toxicities inherent in the existing anti-anxiety drugs. Aqueous methanol leaf extract of Tapinanthus globiferus growing on Azadirachta indica host tree has previously demonstrated significant (p<0.05) anxiolytic effects in mice. This study, therefore, set out to counter-screen this extract for locomotion-suppressant, acute amnesic, sedative (myorelaxant) and hypnotic effects using standard mouse behavioural and biochemical paradigms. The leaf extract (150, 500 and 1500 mg/kg) did not cause significant (p>0.05) alterations in spontaneous locomotor activity, motor coordination/balance, sleep onset or duration, but dose-dependent and significant (p<0.05) increases (63.28±5.63, 65.63±4.12 and 69.18±3.69) in novel object recognition indices of extract-treated compared to 51.54±4.03 and 61.06±2.91 scores in diazepam- and aqua-treated mice, respectively. These findings indicate the aqueous methanol leaf extract is mostly devoid of the evaluated neurobehavioural toxicities and may possess short-term memory enhancement property in mice. These findings may justify the traditional use of Tapinanthus globiferus extracts for memory enhancement.

Keywords:
Cognitive, effects, hypnotic, locomotor, mice, sedative, suppressant

Article Details

How to Cite
Umarudeen, A. M., & Magaji, M. G. (2020). Appraising the Neurobehavioural Toxicity Potential of Aqueous Methanol Leaf Extract of Tapinanthus globiferus Growing on Azadirachta indica. International Neuropsychiatric Disease Journal, 14(2), 1-11. https://doi.org/10.9734/indj/2020/v14i230123
Section
Original Research Article

References

Gureje O, Lasebikan OV, Kola L, Makanjuola AV. Lifetime and 12-month prevalence of mental disorders in the Nigerian Survey of Mental Health and Well-Being. The British Journal of Psychiatry. 2006;188(5):465-471.

Griebel G, Holmes A. 50 years of hurdles and hope in anxiolytic drug discovery. Nature Reviews Drug Discovery. 2013;12: 667–687.

Esan OB, Kola L, Gureje O. Mental disorders and earnings: Results from the Nigerian National Survey of Mental Health and Well-being (NSMHW). J Ment Health Pol Econ. 2012;15:77.

Kessler RC, Merikangas KRN. Epidemiology of mental disorders in children and adolescents. Dialogues Clin Neurosci. 2009;11(1):7-20.

Mishra S, Rekha Swain T, Mohanty M. Adverse drug reaction monitoring of antidepressants in the psychiatry out-patients department of a tertiary care teaching hospital. Journal of Clinical and Diagnostic Research. 2013;7(6):1131-1134.

Lader M. Tylee A, Donoghue J. Withdrawing benzodiazepines in primary care. CNS Drugs. 2009;23:19–34.

Lader M. Benzodiazepine harm: How can it be reduced? British Journal of Clinical Pharmacology. 2014;77:295–301.

Ferguson JM. SSRI antidepressant medications: Adverse effects and tolerability. Primary Care Companion to the Journal of Clinical Psychiatry. 2001;3(1): 22–27.

Machado M, Iskedjian M, Ruiz I, Einarson TR. Remission, dropouts and adverse drug reaction rates in major depressive disorder: A meta-analysis of head-to-head trials. Current Medical Research and Opinion. 2006;22(9):1825-1837.

Wang S, Han C, Bahk W, Lee S, Patkar A. A, Masand PS, Pae C. Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review. Chonnam Med J. 2018;54(2):101–112.

Sayyah M, Eslami K, Alai SS, Kouti LL. Cognitive function before and during treatment with selective serotonin reuptake inhibitors in patients with depression or obsessive-compulsive disorder. Psychiatry Journal; 2015.

[Article ID 5480391]

Nutt D. J. Overview of diagnosis and drug treatments of anxiety disorders. CNS Spectr. 2005;10(1):49–56.

Outhoff K. The pharmacology of anxiolytics. South African Family Practice. 2010;2(2): 99-105.

Dupuy JM, Ostacher MJ, Huffman J, Perlis RH, Nierenberg AAA. Critical review of pharmacotherapy for major depressive disorder. International Journal of Neuro psychopharmacology. 2011;14(10):1417-31.

Khushboo & Sharma B. Antidepressants: mechanism of action, toxicity and possible amelioration. J Appl Biotechnol Bioeng. 2017;3(5):437-448.

Holm KJ, Markham A. Mirtazapine: a review of its use in major depression. Drugs. 1999;57:607–631.

Khasawneh FT, Shankar GS. Minimizing cardiovascular adverse effects of atypical antipsychotic drugs in patients with schizophrenia. Cardiology Research and Practice; 2014.

[Article ID 273060]

The Plant List. Version 1.1.

Matsubara S, Morosinotto T, Bassi R, Christian AL, Fischer-Schliebs E, Lüttge U, Orthen U, Franco AC, Scarano FR, Förster B, Pogson BJ, Osmond CB. Occurrence of the lutein-epoxide cycle in mistletoes of the Loranthaceae and Viscaceae. Planta. 2003;217:868–879.

Moreira BA, Rizzini CM. As famílias loranthaceae e viscaceae da APA de Maricá, Rio De Janeiro, Brasil. Acta Botanica Brasilica. 1997;11:1–8.

Vidal-Russell R, Nickrent DL. The first mistletoes: Origins of aerial parasitism in Santalales. Molecular Phylogenetics and Evolution. 2008;47:523–537.

Adesina SK, Illoh HC, Johnny II, Jacobs IE. African mistletoes (Loranthaceae); ethnopharmacology, chemistry and medicinal values: An update. African Journal of Traditional, Complementary, and Alternative Medicines. AJTCAM. 2013;10: 161–170.

Harquin Simplice F, David Emery T, Hervé Hervé NA. Enhancing spatial memory: Anxiolytic and antidepressant effects of Tapinanthus dodoneifolius (DC) Danser in mice. Neurology Research International; 2014.

[Article ID 974308]

Shehu A, Magaji MG, Yau J, Abubakar A. Ethno-botanical survey of medicinal plants used for the management of depression by Hausa tribes of Kaduna State, Nigeria. Journal of Medicinal Plants Research. 2017;11:562–567.

Emaikwu V, Ndukwe IG, Iyun ORA, Anyam JY. Preliminary phytochemical and antimicrobial activity screening of crude extracts of bird lime (Tapinanthus globiferus). Journal of Applied Sciences and Environmental Management. 2019;23 (2):305.

Abubakar K, Yunus AT, Abubakar MR, Ugwah-Oguejiofor JC, Muhammad AA. Antioxidant and antikindling effect of Tapinanthus globiferus growing on Ficus glumosa in pentylenetetrazole induced kindled rats. African Journal of Biotechnology. 2018;17:73–80.

Odebiyi OO, Sofowora EA. Phytochemical screening of Nigerian medicinal plants II. Lloydia. 1978;41(3):234-46.

Umarudeen AM, Amiu C. Acute toxicological and in-vivo anxiolytic activity screening of aqueous and chloroform fractions of hydroalcoholic Tapinanthus globiferus leaf extracts. World Journal of Innovative Research. 2020;8(5):9-12.

Karthishwaran K, Kamalraj S, Jayabaskaran C, Kurup SS, Sakkir S, Cheruth AJ. GC-MS assisted phytoactive chemical compounds identification and profiling with mineral constituents from biologically active extracts of Aerva javanica (Burm. f) Juss. ex Schult. Notulae Botanicae Horti Agrobotanici Cluj-Napoca. 2018;46(2):517-524.

Umarudeen AM, Magaji GM. Comparative in-vivo anxiolytic efficacy of aqueous and methanol Tapinanthus globiferus leaf extracts. Int Arch Med Health Res. 2019;1 (3):89-93.

Rice MC, O’Brien SJ. Genetic variance of laboratory outbred Swiss mice. Nature. 1980;283:157–161.

Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: Routes of administration and factors to consider. Journal of the American Association for Laboratory Animal Science. 2011;50(5): 600-613.

Umarudeen AM, Magaji GM, Bello SO, Aminu C, Abdullahi MI. Acute anxiolytic activity of aqueous Ampelocissus africana whole-plant, Ficus sycomorus stem bark, and Tapinanthus globiferus leaf extracts in Swiss Albino mice. Int Arch Med Health Res. 2019;1(3):75-81.

Fekadu N, Shibeshi W, Engidawork E. Evaluation of the Antidepressant-like activity of the crude extract and solvent fractions of rosa abyssinica lindley (Rosaceae) using rodent models of depression. Clin Exp Pharmacol. 2016;6:3. 1000207.

Musa AM, Yaro AH, Usman H, Magaji MG, Habu M. Phytochemical and some neuropharmacological studies on the methanolic leaf extracts of Cissus cornifolia [Vitaceae] in mice. International Journal of Pharmacology. 2008;4:145-148.

Stanley JL, Lincoln RJ, Brown TA, McDonald LM, Dawson GR, Reynolds DS. The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines. J Psychopharmacol. 2005;19(3) 221–7.

Deacon RMJ. Measuring motor coordination in mice. Journal of Visualized Experiments. 2013;JoVE(75): e2609.

Hashemi-Firouzi N, Akhavan M, Komaki A, Shahidi S. Effects of acute administration of Urtica dioica on the novel object-recognition task in mice. Avicenna Journal of Neuro Psych Physiology. 2015;2(3): e34150.

Orzelska-Górka J, Berna P, Tutka P, Listos J, Kędzierska E, Fidecka S, Talarek S. Modification of NO-cGMP Pathway differentially affects diazepam- and flunitrazepam-induced spatial and recognition memory impairments in rodents. Neurotox Res. 2020;37(4):1036–1046.

Cascade E, Kalali AH. Use of benzodiazepines in the treatment of anxiety. Psychiatry (Edgmont). 2008;5(9): 21-22.

Seibenhener ML, Wooten MC. Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice. Journal of Visualized Experiments. 2015;96: e52434.

Griffin CE, Kaye AM, Rivera B, Franklin KA, Alan D. Benzodiazepine pharmacology and central nervous system-mediated effects. The Ochsner Journal. 2013;13:214-223.

Baldwin DS, Aitchison K, Bateson A, Curran HV, Davies S, Leonard B, Nutt DJ, Stephens DN, Wilson S. Benzodiazepines: Risks and benefits. A reconsideration. Journal of Psychopharmacology. 2013;27: 967–971.

Abdullahi MH, Kwanashie HO, Danjuma NM. Sedative and anticonvulsant evaluation of Tapinanthus globiferus A. Rich (Loranthaceae) in mice and chicks. Journal of Pharmacy and Bioresources. 2018;15 (1):70–77.

Oremosu A, Edem E, Dosumu O, Osuntoki A. African mistletoe (Loranthaceae) ameliorates cholesterol-induced motor deficit and oxidative stress in 217 adult BALB/c mice. Journal of Experimental and Clinical Anatomy. 2017a;16(2):121-126.

Dunne F, O' Halloran A, Kelly JP. Development of a home cage locomotor tracking system capable of detecting the stimulant and sedative properties of drugs in rats. Progress in Neuro-psychopharmacology & Biological Psychiatry. 2007;31(7):1456-1463.

Islam NU, Khan I, Rauf A, Muhammad N, Shahid M, Shah MR. Antinociceptive, muscle relaxant and sedative activities of gold nanoparticles generated by methanolic extract of Euphorbia milii. BMC Complement Altern Med. 2015;15:160.

Ogunmefun OT, Fasola TR, Saba AB, Oridupa OA. The ethnobotanical, phytochemical and mineral analyses of Phragmanthera Incana (Klotzsch), a species of mistletoe growing on three plant hosts in South-western Nigeria. International Journal of Biomedical Science. 2013;9:37–44.

Abubakar K, Adebisi IM, Ugwah-Oguejiofor JC, Idris GO, Idris B, Mshelia HE. Phytochemical screening and anticonvulsant activity of the residual aqueous fraction of Tapinanthus globiferus Growing on Ficus glums. Herb Med. 2016;2(20):7.

Oremosu AA, Edem EE, Dosumu OO, Osuntoki AA. African Mistletoe (Loranthaceae) enhances spatial and non-spatial working memory in hypercholesterolemia model of Alzheimer’s disease. Nigerian Quarterly Journal of Hospital Medicine. 2017b;27:849–855.

Szurpnicka A, Zjawiony JK, Szterk A. Therapeutic potential of mistletoe in CNS-related neurological disorders and the chemical composition of Viscum species. Journal of Ethnopharmacology. 2019;231: 241–252.

Orhan DD, Aslan M, Sendogdu N, Ergun F, Yesilada E. Evaluation of the hypoglycemic effect and antioxidant activity of three Viscum album subspecies (European mistletoe) in streptozotocin-diabetic rats. Journal of Ethnopharmacology. 2005;98: 95–102.

Ekpenyong EE, Ayodele OA, Linus E. Viscum album enhanced blood serum Brain-Derived Neurotrophic Factor (BDNF) level in the experimental model of Alzheimer’s disease. World Journal of Pharmacy and Pharmaceutical Sciences. 2016;5:157–171.

Adekunle AS, Aline AB, Afolabi OK, Rocha JBT. Determination of free phenolic acids, flavonoid contents and antioxidant capacity of ethanolic extracts obtained from leaves of mistletoe (Tapinanthus globiferus). Asian Journal of Pharmaceutical and Clinical Research. 2012;5:36–41.

Rakotonirina VS, Bum EN, Rakotonirina A, Bopelet M. Sedative properties of the decoction of the rhizome of Cyperus articulatus. Fitoterapia. 2001;72(1): 22–29.