Evidence for the involvement of the GABA-ergic pathway in the anticonvulsant activity of the roots bark aqueous extract of Anthocleista djalonensis A. Chev. (Loganiaceae)
-
Germain Sotoing Taiwe
,
Arielle Larissa Ndieudieu Kouamou
Abstract
Background:
The root bark of Anthocleista djalonensis A. Chev. (Loganiaceae) is widely used in traditional medicine in Northern Cameroon to treat epilepsy and related conditions, such as migraine, insomnia, dementia, anxiety, and mood disorders.
Methods:
To investigate the anticonvulsant effects and the possible mechanisms of this plant, an aqueous extract of Anthocleista djalonensis (AEAD) was evaluated by using animal models of bicuculline-, picrotoxin-, pilocarpine-, and pentylenetetrazole-induced convulsions. Their effects on brain γ-aminobutyric acid (GABA) concentration and GABA-T activity were also determined.
Results:
This extract significantly protected mice against bicuculline-induced motor seizures. It provided 80% protection against picrotoxin-induced tonic-clonic seizures, and strongly antagonized convulsions induced by pilocarpine. AEAD also protected 100% of mice against pentylenetetrazole-induced seizures. Flumazenil, a central benzodiazepine receptor antagonist and FG7142, a partial inverse agonist in the benzodiazepine site of the GABAA receptor complex, were found to have an inhibitory effect on the anticonvulsant action of AEAD in pentylenetetrazole test. Finally, the brain GABA concentration was significantly increased and GABA-T activity was inhibited by AEAD.
Conclusions:
The effects of Anthocleista djalonensis suggested the presence of anticonvulsant properties that might involve an action on benzodiazepine and/or GABA sites in the GABAA receptor complex or by modulating GABA concentration in the central nervous system (CNS).
Acknowledgments
This work was supported by a research grant from the World Academy of Sciences for the Advancement of Science in Developing Countries (TWAS), Trieste, Italy (No. 15-183 RG/BIO/AFAC_I–FR3240287065) awarded to Dr. Germain Sotoing Taiwe. We are grateful for the financial support provided by the TWAS.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by research grants from the World Academy of Sciences for the Advancement of Science in Developing Countries (TWAS), Trieste, Italy (No. 15-183 RG/BIO/AFAC_I – FR3240287065).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication. The authors declare that they have no competing interests.
References
1. Njamnshi AK, Bissek AC, Yepnjio FN, Tabah EN, Angwafor SA, Kuate CT, et al. A community survey of knowledge, perceptions, and practice with respect to epilepsy among traditional healers in the Batibo Health District, Cameroon. Epilepsy Behav 2010;17:95–102.10.1016/j.yebeh.2009.10.018Search in Google Scholar
2. WHO. Epilepsy: fact sheet. Available from: http://www.who.int/mediacentre/factsheets/fs999/en/. May 2017.Search in Google Scholar
3. Macdonald RL, Greenfield JL. Mechanisms of action of new antiepileptic drugs. Curr Opin Neurol 1997;10:121–8.10.1097/00019052-199704000-00009Search in Google Scholar
4. Loeb J. Identifying targets for preventing epilepsy using systems biology. Neurosci Lett 2011;497:205–12.10.1016/j.neulet.2011.02.041Search in Google Scholar
5. Giovany MP, Cícero FB, Fúlvio AS, Marta AC, Alinne FT, Maria LF, et al. Piperine decreases pilocarpine-induced convulsions by GABAergic mechanisms. Pharmacol Biochem Behav 2013;104:144–53.10.1016/j.pbb.2013.01.002Search in Google Scholar
6. Gorji A, Khaleghi GM. History of epilepsy in Medieval Iranian medicine. Neurosci Biobehav Rev 2001;25:455–61.10.1016/S0149-7634(01)00025-2Search in Google Scholar
7. Nsour W, Lau C, Wong I. Review on phytotherapy in epilepsy. Seizure 2000;9:96–107.10.1053/seiz.1999.0378Search in Google Scholar
8. Kerharo J, Adam J. La pharmacopée traditionnelle sénégalaise. Plantes Médicinales et Toxiques Vigot et Frères, Paris, 1974:268–73.Search in Google Scholar
9. Pousset J. African medicinal plants: practical use. Plantes médicinales africaines: utilisation pratique. 1989.Search in Google Scholar
10. Arbonnier M. Arbres, Arbustes et Lianes des Zones Sfleches d’Afrique de l’Ouest, vol. 2. Edition CIRAD-MNHN-UICN, Montpellier, France, 2000.Search in Google Scholar
11. Okoli A, Iroegbu C. Evaluation of extracts of Anthocleista djalonensis, Nauclea latifolia and Uvaria afzalii for activity against bacterial isolates from cases of non-gonococcal urethritis. J Ethnopharmacol 2004;92:135–44.10.1016/j.jep.2003.12.015Search in Google Scholar
12. Gorin PA, Mazurek M. Further studies on the assignment of signals in 13C magnetic resonance spectra of aldoses and derived methyl glycosides. Can J Chem 1975;53:1212–23.10.1139/v75-168Search in Google Scholar
13. Okorie DA. A new phthalide and xanthones from Anthocleista djalonensis and Anthocleista vogelli. Phytochemistry 1976;15:1799–800.10.1016/S0031-9422(00)97499-5Search in Google Scholar
14. Onocha PA, Okorie DA, Connolly JD, Roycroft DS. Monoterpene diol, iridoid glucoside and dibenzo-α-pyrone from Anthocleista djalonensis. Phytochemistry 1995;40:1183–9.10.1016/0031-9422(95)00121-MSearch in Google Scholar
15. Watt JM, Breyer-Brandwijk MG. The Medicinal and Poisonous Plants of Southern Africa. Ulster Med J 1933;2:112.Search in Google Scholar
16. Melo MS, Santana MT, Guimarães AG, Siqueira RS, Sousa DP, Santos R, et al. Bioassay-guided evaluation of central nervous system effects of citronellal in rodents. Rev Bras Farmacog 2011;21:697–703.10.1590/S0102-695X2011005000124Search in Google Scholar
17. Robinson T. The biochemistry of alkaloids. Berlin: Springer, 1981.10.1007/978-3-642-61830-7Search in Google Scholar
18. Taiwe GS, Tchoya TB, Menanga JR, Dabole B, De Waard M. Anticonvulsant activity of an active fraction extracted from Crinum jagus L. (Amaryllidaceae), and its possible effects on fully kindled seizures, depression-like behaviour and oxidative stress in experimental rodent models. J Ethnopharmacol 2016;194:421–33.10.1016/j.jep.2016.10.023Search in Google Scholar
19. Ribéreau-Gayon J, Peynaud E. Les composés phénoliques des végétaux. Traité d’œnologie. Paris: Édition Dunod, 1968.Search in Google Scholar
20. Trease G, Evans W. Pharmacognosy. London: Ballière Tindall Press, 1983.Search in Google Scholar
21. Beretz A, Haag-Berrurier M, Anton R. Choix de méthodes pharmacologiques pour l’étude des activités de l’aubépine. Plantes médicinales et phytothérapie 1978;4:305–14.Search in Google Scholar
22. Wagner H, Bladt S. Plant drug analysis: a thin layer chromatography Atlas, 2nd ed. Berlin: Springer, 1996:447.10.1007/978-3-642-00574-9Search in Google Scholar
23. Taiwe GS, Dabole B, Tchoya TB, Menanga JR, Dzeufiet PD, De Waard M. Anticonvulsant effects of iridoid glycosides fraction purified from Feretia apodanthera Del. (Rubiaceae) in experimental mice models of generalized tonic-clonic seizures. BMC Complement Altern Med 2016;16:285.10.1186/s12906-016-1269-8Search in Google Scholar
24. Racine RJ. Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalogr Clin Neurophysiol 1972;32:281–94.10.1016/0013-4694(72)90177-0Search in Google Scholar
25. Palmer GC, Murray RJ, Cramer CL, Stagnitto ML, Knowles MK, Freedman LR, et al. [S]-AR-R 15896AR-A Novel Anticonvulsant: acute safety, pharmacokinetic and pharmacodynamic properties. J Pharm Exp Ther 1999;288:121–32.10.1016/S0022-3565(24)37933-9Search in Google Scholar
26. Vezzani A, Moneta D, Richichi C, Aliprandi M, Burrows SJ, Ravizza T, et al. Functional role of inflammatory cytokines and antiinflammatory molecules in seizures and epileptogenesis. Epilepsia 2002;43(s5):30–5.10.1046/j.1528-1157.43.s.5.14.xSearch in Google Scholar PubMed
27. Buznego MT, Pérez-Saad H. Acute effect of an extract of Ambrosia paniculata (Willd.) OE Schultz (mugwort) in several models of experimental epilepsy. Epilepsy Behav 2004;5:847–51.10.1016/j.yebeh.2004.07.006Search in Google Scholar PubMed
28. Yemitan O, Adeyemi O. CNS depressant activity of Lecaniodiscus cupanioides. Fitoterapia 2005;76:412–8.10.1016/j.fitote.2005.02.010Search in Google Scholar PubMed
29. Aguiar CC, Almeida AB, Araújo PV, Vasconcelos GS, Chaves EM, do Vale OC, et al. Anticonvulsant effects of agomelatine in mice. Epilepsy Behav 2012;24:324–8.10.1016/j.yebeh.2012.04.134Search in Google Scholar PubMed
30. Taiwe GS, Moto FC, Pale S, Kandeda AK, Dawe A, Kouemou N, et al. Extracts of Feretia apodanthera Del. demonstrated anticonvulsant activities against seizures induced by chemicals and maximal electroshock. Epilepsy Res 2016;127:30–9.10.1016/j.eplepsyres.2016.08.009Search in Google Scholar
31. Ngo Bum E, Taiwe G, 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 Behav 2009;15:434–40.10.1016/j.yebeh.2009.05.014Search in Google Scholar
32. Taiwe GS, Ngo 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 extracts in murine models. Int J Pharmacol 2010;6:326–33.10.3923/ijp.2010.364.371Search in Google Scholar
33. Lowe IP, Robins E, Eyerman GS. The fluorimetric measurement of glutamic decarboxylase and its distribution in brain. J Neurochem 1958;3:8–18.10.1111/j.1471-4159.1958.tb12604.xSearch in Google Scholar
34. Nayak P, Chatterjee A. Effects of aluminium exposure on brain glutamate and GABA systems: an experimental study in rats. Food Chem Toxicol 2001;39:1285–9.10.1016/S0278-6915(01)00077-1Search in Google Scholar
35. Litchfield J, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharm Exp Ther 1949;96:99–113.10.1016/S0022-3565(25)03549-9Search in Google Scholar
36. Sperber E, Wurpel J, Zhao D, Moshé SL. Evidence for the involvement of nigral GABA A receptors in seizures of adult rats. Brain Res 1989;480:378–82.10.1016/0006-8993(89)90211-4Search in Google Scholar
37. Mustafa A, Ali A. A substance in broad beans (Vicia faba) is protective against experimentally induced convulsions in mice. Epilepsy Behav 2008;12:25–9.10.1016/j.yebeh.2007.08.016Search in Google Scholar PubMed
38. Nascimento V, Oliveira A, Freitas R, Sousa F, Vasconcelos S, Viana G, et al. Pilocarpine-induced status epilepticus: monoamine level, muscarinic and dopaminergic receptors alterations in striatum of young rats. Neurosci Lett 2005;383:165–70.10.1016/j.neulet.2005.04.006Search in Google Scholar PubMed
39. Quintans Júnior LJ, Almeida JR, Lima JT, Nunes XP, Siqueira JS, Oliveira LE, et al. Plants with anticonvulsant properties: a review. Rev Bras Farmacogn 2008;18:798–819.10.1590/S0102-695X2008000500026Search in Google Scholar
40. Velisek L, Veliskova J, Moshé SL. Developmental seizure models. Ital J Neurol Sci 1995;16:127–33.10.1007/BF02229085Search in Google Scholar PubMed
41. Velisek L. Models of chemically-induced acute seizures. Models of Seizures and Epilepsy 2006:127–52.10.1016/B978-012088554-1/50013-XSearch in Google Scholar
42. Kupferberg H, Schmutz M. Screening of new compounds and the role of the pharmaceutical industry. Epilepsy: a comprehensive textbook Philadelphia: Lippincott-Raven, 1997:1417–34.Search in Google Scholar
43. Löscher W, Schmidt D. Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res 1988;2:145–81.10.1016/0920-1211(88)90054-XSearch in Google Scholar
44. Pérez-Saad H, Buznego MT. Behavioral and antiepileptic effects of acute administration of the extract of the plant Cestrum nocturnum Lin (lady of the night). Epilepsy Behav 2008;12:366–72.10.1016/j.yebeh.2007.12.012Search in Google Scholar
45. Evans AK, Lowry CA. Pharmacology of the β-carboline FG 7142, a partial inverse agonist at the benzodiazepine allosteric site of the GABAA receptor: neurochemical, neurophysiological, and behavioral effects. CNS Drug Rev 2007;13:475–501.10.1111/j.1527-3458.2007.00025.xSearch in Google Scholar
46. Chapman AG, Meldrum BS, Mendes E. Acute anticonvulsant activity f structural analogue of valproic acid and change in brain GABA and aspartate content. Life Sci 1983;32:2023–31.10.1016/0024-3205(83)90054-1Search in Google Scholar
47. Saad SP. 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;24:839–40.10.1111/j.2042-7158.1972.tb08900.xSearch in Google Scholar
48. Kelly KM, Gross RA, Macdonald RL. Valproic acid selectively reduces the low-threshold (T) calcium current in rat nodose neurons. Neuroscience Lett 1990;116:233–8.10.1016/0304-3940(90)90416-7Search in Google Scholar
49. Sherif FM, Saleem AS. Basic aspects of GABA transaminase in neuropsychiatric disorders. Clin Biochem 1995;28:145–54.10.1016/0009-9120(94)00074-6Search in Google Scholar
50. Aps JK, Martens LC. Review: the physiology of saliva and transfer of drugs into saliva. Forensic Sci Int 2005;150:119–31.10.1016/j.forsciint.2004.10.026Search in Google Scholar PubMed
©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Natural product for the treatment of Alzheimer’s disease
- Behavior and Neuroprotection
- Evidence for the involvement of the GABA-ergic pathway in the anticonvulsant activity of the roots bark aqueous extract of Anthocleista djalonensis A. Chev. (Loganiaceae)
- Cardiovascular Function
- Cutaneous temperature sensitivity alteration in subjects with chronic stroke sequelae – pharmacological perspectives
- Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia
- Oxidative Stress
- Phellinus rimosus improves mitochondrial energy status and attenuates nephrotoxicity in diabetic rats
- Hepatoprotective effects of Vaccinium arctostaphylos against CCl4-induced acute liver injury in rats
- The impact of vitamin C on the relationship among inflammation, lipid peroxidation and platelet activation during analgesic nephropathy in rats
- Phytotherapy
- Antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice
- Amelioration of hyperglycemia and associated metabolic abnormalities by a combination of fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) in experimental diabetes
- An ethanolic extract of Desmodium adscendens exhibits antipsychotic-like activity in mice
Articles in the same Issue
- Frontmatter
- Review
- Natural product for the treatment of Alzheimer’s disease
- Behavior and Neuroprotection
- Evidence for the involvement of the GABA-ergic pathway in the anticonvulsant activity of the roots bark aqueous extract of Anthocleista djalonensis A. Chev. (Loganiaceae)
- Cardiovascular Function
- Cutaneous temperature sensitivity alteration in subjects with chronic stroke sequelae – pharmacological perspectives
- Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia
- Oxidative Stress
- Phellinus rimosus improves mitochondrial energy status and attenuates nephrotoxicity in diabetic rats
- Hepatoprotective effects of Vaccinium arctostaphylos against CCl4-induced acute liver injury in rats
- The impact of vitamin C on the relationship among inflammation, lipid peroxidation and platelet activation during analgesic nephropathy in rats
- Phytotherapy
- Antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice
- Amelioration of hyperglycemia and associated metabolic abnormalities by a combination of fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) in experimental diabetes
- An ethanolic extract of Desmodium adscendens exhibits antipsychotic-like activity in mice
