Potential of an aqueous extract of Lippia multiflora Moldenke (Verbenaceae) in the treatment of anxiety disorders: Possible involvement of serotoninergic transmission

Authors

  • Joseph Ngaibi Department of Biological Sciences, Faculty of Science, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon.
  • Germain Sotoing Taiwe Department of Zoology and Animal Physiology, Faculty of Science, University of Buea, Cameroon, P.O. Box 63, Buea, Cameroon.
  • Jacqueline Stephanie Kameni Njapdounke Department of Biological Sciences, Faculty of Science, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon.
  • Bigued Department of Biological Sciences, Faculty of Science, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon.
  • Yvette Nguezeye Centre for Research on Medicinal Plants and Traditional Medicine, Institute of Medical Research and Medicinal Plants Studies, P.O. Box 13033, Yaounde, Cameroon.
  • Neteydji Sidiki Department of Biological Sciences, Faculty of Science, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon.
  • Elisabeth Ngo Bum Department of Biological Sciences, Faculty of Science, University of Maroua, P.O. Box 814, Maroua, Cameroon.

DOI:

https://doi.org/10.30574/gscbps.2021.14.3.0079

Keywords:

Lippia multiflora, Anxiolytic, Serotonin receptors, Brain, Traditional medicine

Abstract

Ethnopharmacological relevance: The leaves and stems of Lippia multiflora Moldenke (Verbenaceae) are used in traditional medicine to treat depression, anxiety and epilepsy.

Aim of the study: The present study investigated the anxiolytic-like effects of Lippia multiflora aqueous extracts in experimental models of anxiety.

Materials and methods: Elevated plus maze and open field tests were used to evaluate anxiety and exploratory behaviour. The possible mechanism of action of Lippia multiflora were investigated after pretreatment of animal with agonist and antagonist of serotonin receptors, such as: mCPP, a partial agonist at the 5-HT2C receptors; Way-100635, a selective 5-HT1A receptors antagonist; and DOI, the 5-HT2A/2C receptors agonist. The levels of monoamine neurotransmitters were evaluated in the brain.

Results: In the elevated plus maze, Lippia multiflora increased the number of entries into and percentage of time in open arms, and reduced rearing, head dipping, and percentage of time in closed arms. These effects were blocked with the agonist and antagonist of serotonin receptors. In the open field, Lippia multiflora increased crossing and reduced rearing and defecation. The endogenous levels of noradrenaline, dopamine and serotonin in the brain homogenates remain comparable to that distilled water-treated animals.

Conclusion: It could be concluded that Lippia multiflora aqueous extracts, used in traditional medicine in Cameroon for the treatment of depression, anxiety and epilepsy seemed to possess anxiolytic properties in mice. These effects might be mediated by serotonin receptors, but not by modulation of the levels of monoamine neurotransmitters when the extract is administered once after one hour.

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References

Pelissolo A. Troubles anxieux et névrotiques. EMC-AKOS Traité Médecine. 2012; 1-11.

Boyd CP, Gullone E, Kostanski M, Ollendick TH, Shek DT. Prevalence of anxiety and depression in Australian adolescents: Comparisons with worldwide data. The Journal of Genetic Psychology. 2000; 161(4): 479-92.

Costello EJ, Mustillo S, Erkanli A, Keeler G, Angold A. Prevalence and development of psychiatric disorders in childhood and adolescence. Archives of general psychiatry. 2003; 60(8): 837-44.

Nemeroff CB. The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacology bulletin. 2003; 37(4): 133-46.

Taïwe G, Bum E, Dimo T, Talla E, Weiss N, Dawe A, et al. Antidepressant, myorelaxant and anti-anxiety-like effects of Nauclea latifolia smith (Rubiaceae) roots extract in murine models. International journal of pharmacology. 2010; 6(4): 364-71.

Saad S. Administration of CNS depressant drugs like barbiturates, hydantoin and diazepam etc. can restore the isoniazid induced fall in brain GABA levels. J Pharm Pharmacol. 1972; 24: 839-40.

Ninan PT. The functional anatomy, neurochemistry, and pharmacology of anxiety. Journal of Clinical Psychiatry. 1999; 60: 12-7.

Hoyer D, Martin G. 5-HT receptor classification and nomenclature: towards a harmonization with the human genome. Neuropharmacology. 1997; 36(4-5): 419-28.

Feighner JP, Boyer WF. Serotonin-1A anxiolytics: an overview. Psychopathology. 1989; 22(Suppl. 1): 21-6.

Heisler LK, Chu H-M, Brennan TJ, Danao JA, Bajwa P, Parsons LH, et al. Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proceedings of the National Academy of Sciences. 1998; 95(25): 15049-54.

Adjanohoun É. Contribution aux études ethnobotaniques et floristiques au Togo: rapport présenté à l'ACCT: Agence de coopération culturelle et technique. 1986.

Akoegninou A, Adjanohoun E, Adjakidje M, Ahyi L, Ake Assi A, Akoegninou J, et al. Contribution aux études ethnobotaniques et floristiques en République Populaire du Bénin. Médecine traditionnelle et pharmacopée Agence de coopération culturelle et technique, (ACCT), Paris. 1989; 895.

Arbonnier M. Arbres, arbustes et lianes des zones sèches d'Afrique de l'Ouest: Editions Quae. 2009.

González-Trujano ME, Hernández-Sánchez LY, Muñoz Ocotero V, Dorazco-González A, Guevara Fefer P, Aguirre-Hernández E. Pharmacological evaluation of the anxiolytic-like effects of Lippia graveolens and bioactive compounds. Pharmaceutical biology. 2017; 55(1): 1569-76.

Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. Journal of Cerebral Blood Flow & Metabolism. 2020; 40(9): 1769-77.

Organization WH. General guidelines for methodologies on research and evaluation of traditional medicine. World Health Organization. 2000.

Lister RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology. 1987; 92(2): 180-5.

Bourin M, Petit‐Demoulière B, Nic Dhonnchadha B, Hascöet M. Animal models of anxiety in mice. Fundamental & clinical pharmacology. 2007; 21(6): 567-74.

Bum EN, Taïwe GS, Moto F, Ngoupaye G, Nkantchoua G, Pelanken M, et al. Anticonvulsant, anxiolytic, and sedative properties of the roots of Nauclea latifolia Smith in mice. Epilepsy & Behavior. 2009; 15(4): 434-40.

Kim C, Speisky M, Kharouba S. Rapid and sensitive method for measuring norepinephrine, dopamine, 5-hydroxytryptamine and their major metabolites in rat brain by high-performance liquid chromatography: differential effect of probenecid, haloperidol and yohimbine on the concentrations of biogenic amines and metabolites in various regions of rat brain. Journal of Chromatography A. 1987; 386: 25-35.

Rex A, Morgenstern E, Fink H. Anxiolytic-like effects of Kava-Kava in the elevated plus maze test—a comparison with diazepam. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2002; 26(5): 855-60.

Faustino TT, Almeida RBd, Andreatini R. Medicinal plants for the treatment of generalized anxiety disorder: a review of controlled clinical studies. Brazilian Journal of Psychiatry. 2010; 32(4): 429-36.

Hilakivi-Clarke L, Turkka J, Lister R, Linnoila M. Effects of early postnatal handling on brain β-adrenoceptors and behavior in tests related to stress. Brain research. 1991; 542(2): 286-92.

Liu Z, Silva J, Shao AS, Liang J, Wallner M, Shao XM, et al. Flavonoid compounds isolated from Tibetan herbs, binding to GABAA receptor with anxiolytic property. Journal of Ethnopharmacology. 2021; 267: 113630.

Karim N, Jia Z, Zheng X, Cui S, Chen W. A recent review of citrus flavanone naringenin on metabolic diseases and its potential sources for high yield-production. Trends in Food Science & Technology. 2018; 79: 35-54.

Antunes MS, Cattelan Souza L, Ladd FVL, Ladd AABL, Moreira AL, Bortolotto VC, et al. Hesperidin Ameliorates Anxiety-Depressive-Like Behavior in 6-OHDA Model of Parkinson’s Disease by Regulating Striatal Cytokine and Neurotrophic Factors Levels and Dopaminergic Innervation Loss in the Striatum of Mice. Molecular Neurobiology. 2020; 57: 3027-41.

Pellow S, Chopin P, File SE, Briley M. Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. Journal of neuroscience methods. 1985; 14(3): 149-67.

Bum EN, Soudi S, Ayissi E, Dong C, Lakoulo N, Maidawa F, et al. Anxiolytic activity evaluation of four medicinal plants from Cameroon. African Journal of Traditional, Complementary and Alternative Medicines. 2011; 8(5S).

Moto FC, Arsa’a A, Ngoupaye GT, Taiwe GS, Njapdounke JS, Kandeda AK, et al. Anxiolytic and antiepileptic properties of the aqueous extract of Cissus quadrangularis (Vitaceae) in mice pilocarpine model of epilepsy. Frontiers in pharmacology. 2018; 9: 751.

Bielau H, Steiner J, Mawrin C, Truebner K, Brisch R, MEYER‐LOTZ G, et al. Dysregulation of GABAergic neurotransmission in mood disorders: a postmortem study. Annals of the New York Academy of Sciences. 2007; 1096(1): 157-69.

Ressler KJ, Nemeroff CB. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depression and anxiety. 2000; 12(S1): 2-19.

Rincón-Cortés M, Gagnon KG, Dollish HK, Grace AA. Diazepam reverses increased anxiety-like behavior, social behavior deficit, and dopamine dysregulation following withdrawal from acute amphetamine. Neuropsychopharmacology. 2018; 43(12): 2418-25.

Bourin M, Dhonnchadha BdÁN, Colombel MC, Dib M, Hascoët M. Cyamemazine as an anxiolytic drug on the elevated plus maze and light/dark paradigm in mice. Behavioural brain research. 2001; 124(1): 87-95.

Forster EA, Cliffe IA, Bill DJ, Dover GM, Jones D, Reilly Y, et al. A pharmacological profile of the selective silent 5-HT1A receptor antagonist, WAY-100635. European journal of pharmacology. 1995; 281(1): 81-8.

Martínez-Mota L, Estrada-Camarena E, López-Rubalcava C. Indorenate produces antidepressant-like actions in the rat forced swimming test via 5-HT 1A receptors. Psychopharmacology. 2002; 165(1): 60-6.

Harada K, Yamaji T, Matsuoka N. Activation of the serotonin 5-HT2C receptor is involved in the enhanced anxiety in rats after single-prolonged stress. Pharmacology Biochemistry and Behavior. 2008; 89(1): 11-6.

Taïwe GS, Bum EN, Talla E, Dimo T, Sidiki N, Dawe A, et al. Evaluation of antinociceptive effects of Crassocephalum bauchiense Hutch (Asteraceae) leaf extract in rodents. Journal of Ethnopharmacology. 2012; 141(1): 234-41.

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Published

2021-03-30

How to Cite

Joseph Ngaibi, Germain Sotoing Taiwe, Jacqueline Stephanie Kameni Njapdounke, Bigued, Yvette Nguezeye, Neteydji Sidiki, & Elisabeth Ngo Bum. (2021). Potential of an aqueous extract of Lippia multiflora Moldenke (Verbenaceae) in the treatment of anxiety disorders: Possible involvement of serotoninergic transmission. GSC Biological and Pharmaceutical Sciences, 14(3), 277–289. https://doi.org/10.30574/gscbps.2021.14.3.0079

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