Abstract
Background:
Desmodium adscendens extract (DAE) is used traditionally in Ghana for the management of psychosis. The present study aimed at providing pharmacological evidence for its ethnomedical use by testing the hypothesis that an ethanolic extract of Desmodium adscendens may possess antipsychotic properties.
Methods:
The primary behavioral effects of DAE on the central nervous system of mice were investigated using Irwin’s test paradigm. Novelty-induced and apomorphine-induced locomotor and rearing behaviors in mice were explored in an open-field observational test system. Apomorphine-induced cage climbing test in mice was used as the antipsychotic animal model. The ability of DAE to induce catalepsy and enhance haloperidol-induced catalepsy was also investigated in mice.
Results:
The DAE produced sedation, cholinergic-, and serotonergic-like effects in mice when evaluated using the Irwin’s test. No lethality was observed after 24 h post-treatment. The LD50 in mice was estimated to be greater than 3000 mg/kg. The DAE significantly decreased the frequency of novelty- and apomorphine-induced rearing and locomotor activities in mice. It also significantly lowered the frequency and duration of apomorphine-induced climbing activities in mice. It did not induce any cataleptic event in naïve mice but only significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg.
Conclusions:
The ethanolic extract of Desmodium adscendens exhibited antipsychotic-like activities in mice. Motor side effects are only likely to develop at higher doses of the extract.
Acknowledgments
The authors acknowledge the support provided by Esther Benewaa in the apomorphine-induced cage-climbing experiments. We are also grateful to Constance Agbemelo-Tsomafo, Shirley Nyarko Adu-Poku and other technical staff at the Animal Experimentation unit of the NMIMR, Accra, Ghana and the technical staff of the Animal Resource Center, Health Sciences Center, Kuwait University Kuwait, for their immense contributions during the experiments conducted there.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: The research work described in this article was financially supported by the Office of Research, Innovation and Development (ORID), University of Ghana, Accra, Ghana, grant awarded to Dr. Patrick Amoateng (reference number: URF/6/ILG-002/2012-2013). The research paper was also supported by the University of Ghana-Carnegie Next Generation of Academics in Africa Project with funding from the Carnegie Corporation of New York. Thomas K. Karikari was funded by the Biotechnology and Biological Sciences Research Council (BBSRC; http://www.bbsrc.ac.uk) grant number BB/J014532/1 through the Midlands Integrative Biosciences Training Partnership.
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.
References
1. Lupski JR. Schizophrenia: incriminating genomic evidence. Nature 2008;455:178–9.10.1038/455178aSearch in Google Scholar
2. Garety PA, Kuipers E, Fowler D, Freeman D, Bebbington PE. A cognitive model of the positive symptoms of psychosis. Psych Med 2001;31:189–95.10.1017/S0033291701003312Search in Google Scholar
3. Kay SR, Flszbein A, Opfer LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bull 1987;13:261.10.1093/schbul/13.2.261Search in Google Scholar
4. Addington J, Addington D, Maticka-Tyndale E. Cognitive functioning and positive and negative symptoms in schizophrenia. Schizophrenia Res 1991;5:123–34.10.1016/0920-9964(91)90039-TSearch in Google Scholar
5. Brenner HD, Kraemer S, Hermanutz M, Hodel B. Cognitive treatment in schizophrenia. In: Straube ER, Hahlweg K, editors. Schizophrenia: concepts, vulnerability, and intervention. Berlin, Heidelberg: Springer, 1990:161–91.10.1007/978-3-642-74308-5_9Search in Google Scholar
6. Ninan PT. Pharmacological management of schizophrenia. In: Bellack AS, editor. A clinical guide for the treatment of schizophrenia. Boston, MA: Springer;1989:23–42.10.1007/978-1-4757-8979-9_2Search in Google Scholar
7. Breier A, Berg PH. The psychosis of schizophrenia: prevalence, response to atypical antipsychotics, and prediction of outcome. Biol Psychiatry 1999;46:361–64.10.1016/S0006-3223(99)00040-2Search in Google Scholar
8. Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. New Engl J Med 2009;360:225–35.10.1056/NEJMoa0806994Search in Google Scholar
9. Arana GW. An overview of side effects caused by typical antipsychotics. J Clin Psychiatry 2000;61:5–11;discussion 12–13.Search in Google Scholar
10. Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatment meta-analysis. Lancet 2013;382:951–62.10.1016/S0140-6736(13)60733-3Search in Google Scholar
11. Peluso MJ, Lewis SW, Barnes TR, Jones PB. Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs. Br J Psychiatry 2012;200:387–92.10.1192/bjp.bp.111.101485Search in Google Scholar PubMed
12. Englisch S, Zink M. Treatment-resistant schizophrenia: evidence-based strategies. Mens Sana Monographs 2012;10: 20–32.10.4103/0973-1229.91588Search in Google Scholar PubMed PubMed Central
13. Crossley NA, Constante M, McGuire P, Power P. Efficacy of atypical v. typical antipsychotics in the treatment of early psychosis: meta-analysis. Br J Psychiatry 2010;196:434–39.10.1192/bjp.bp.109.066217Search in Google Scholar
14. O’Reilly D, Craig D, Phillips L, Goeree R, Tarride J-E, Parfrey P. Costs of new atypical antipsychotic agents schizophrenia: does unrestricted access reduce hospital utilization? Healthcare Policy 2007;3:58–79.10.12927/hcpol.2007.19174Search in Google Scholar
15. Burns JK, Jhazbhay K, Emsley RA. Causal attributions, pathway to care and clinical features of first-episode psychosis: a South African perspective. Int J Soc Psychiatry 2011;57:538–45.10.1177/0020764010390199Search in Google Scholar
16. Merritt-Davis OB, Keshavan MS. Pathways to care for African Americans with early psychosis. Psychiatry Serv 2006;57: 1043–44.10.1176/ps.2006.57.7.1043Search in Google Scholar
17. Gureje O, Nortje G, Makanjuola V, Oladeji B, Seedat S, Jenkins R. The role of global traditional and complementary systems of medicine in treating mental health problems. Lancet Psychiatry 2015;2:168–77.10.1016/S2215-0366(15)00013-9Search in Google Scholar
18. Omonzejele PF. African concepts of health, disease, and treatment: an ethical inquiry. Explore (New York, NY) 2008;4:120–26.10.1016/j.explore.2007.12.001Search in Google Scholar
19. Koenig HG. Research on religion, spirituality, and mental health: a review. Can J Psychiatry 2009;54:283–91.10.1177/070674370905400502Search in Google Scholar
20. Anyinam C. Availability, accessibility, acceptability, and adaptibility: four attributes of African ethno-medicine. Soc Sci Med 1987;25:803–11.10.1016/0277-9536(87)90038-4Search in Google Scholar
21. Kline NS. Use of Rauwolfia serpentina Benth in neuropsychiatric conditions. Ann New York Acad Sci 1954;59:107–32.10.1111/j.1749-6632.1954.tb45922.xSearch in Google Scholar PubMed
22. Zhang ZJ. Therapeutic effects of herbal extracts and constituents in animal models of psychiatric disorders. Life Sci 2004;75:1659–99.10.1016/j.lfs.2004.04.014Search in Google Scholar
23. Mshana NR, Abbiw DK, Addae-Mensah I, Adjanouhoun E, Ahyi MRA, Ekpere JA, et al. Traditional and medicine pharmacopoiea: contribution to the revision of Ethnobotanical and Floristic studies in Ghana: Scientific,Technical and Research Commission of the Organization of African Unity (OAU/STRC); 2000.Search in Google Scholar
24. Dokosi OB. Herbs of Ghana. Accra: Ghana Universities Press, 1998.Search in Google Scholar
25. N’Gouemo P, Baldy-Moulinier M, Nguemby-Bina C. Effects of an ethanolic extract of Desmodium adscendens on central nervous system in rodents. J Ethnopharmacol 1996;52:77–83.10.1016/0378-8741(96)01389-XSearch in Google Scholar
26. Evans WC. Trease and Evans’ Pharmacognosy, 15th ed. Edinburgh: Saunders Ltd, 2002.Search in Google Scholar
27. Irwin S. Comprehensive observational assessment: a systematic,quantitative procedure for assessing the behavioural and physiologic state of the mouse. Psychoparmacologia 1968;13:222–56.10.1007/BF00401402Search in Google Scholar
28. Davis AS, Jenner P, Marsden CD. A comparison of motor behaviours in groups of rats distinguished by their climbing response to apomorphine. Br J Pharmacol 1986;87:129–37.10.1111/j.1476-5381.1986.tb10164.xSearch in Google Scholar
29. Sanberg PR, Bunsey MD, Giordano M, Norman AB. The catalepsy test: its ups and downs. Behav Neurosci 1988;102:748.10.1037/0735-7044.102.5.748Search in Google Scholar
30. Taïwe GS, Bum EN, Talla E, Dawe A, Moto FCO, Ngoupaye GT, et al. Antipsychotic and sedative effects of the leaf extract of Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) in rodents. J Ethnopharmacol 2012;143:213–20.10.1016/j.jep.2012.06.026Search in Google Scholar
31. Pemminati S, Nair V, Dorababu P, Gopalakrishna H, Pai M. Effect of ethanolic leaf extract of Ocimum sanctum on haloperidol-induced catalepsy in albino mice. Indian J Pharmacol 2007;39:87.10.4103/0253-7613.32526Search in Google Scholar
32. Trevor A, Way W. Sedative-hypnotics. In: Katzung B, Masters S, Trevor A, editors, 12th ed. Basic and Clinical pharmacology. USA: McGraw-Hill Lange, 2012:373–86.Search in Google Scholar
33. Arnt J, Hyttel J. Facilitation of 8-OHDPAT-induced forepaw treading of rats by the 5-HT 2 agonist DOI. Eur J Pharmacol 1989;161:45–51.10.1016/0014-2999(89)90178-7Search in Google Scholar
34. Rang R, Dale M, Ritter J, Flower R, Henderson G. Cholinergic transmission. Rang & Dale’s Pharmacology, 7th ed. Edinburgh, UK: Elsevier Churchill Livingstone, 2012:158.10.1016/B978-0-7020-3471-8.00013-5Search in Google Scholar
35. Zaman A, Khan MSS, Akter L, Syeed SH, Akter J, Al Mamun A, et al. Exploring new pharmacology and toxicological screening and safety evaluation of one widely used formulation of Nidrakar Bati from South Asia region. BMC Complement Altern Med 2015;15:121.10.1186/s12906-015-0635-2Search in Google Scholar PubMed PubMed Central
36. Nesa L, Munira S, Mollika S, Islam M, Choin H, Chouduri AU, et al. Evaluation of analgesic, anti-inflammatory and CNS depressant activities of methanolic extract of Lawsonia inermis barks in mice. Avicenna J Phytomed 2014;4:287–96.10.9734/BJPR/2014/7845Search in Google Scholar
37. Stoof J, Kebabian J. Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sci 1984;35:2281–96.10.1016/0024-3205(84)90519-8Search in Google Scholar
38. Haleem DJ, Ikram H, Haleem MA. Inhibition of apomorphine-induced conditioned place preference in rats co-injected with buspirone: relationship with serotonin and dopamine in the striatum. Brain Res 2014;1586:73–82.10.1016/j.brainres.2014.06.022Search in Google Scholar
39. Lipska BK, Weinberger DR. To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology 2000;23:223–39.10.1016/S0893-133X(00)00137-8Search in Google Scholar
40. Gardner DM, Baldessarini RJ, Waraich P. Modern antipsychotic drugs: a critical overview. Can Med Assoc J 2005;172:1703–11.10.1503/cmaj.1041064Search in Google Scholar
41. Costall B, Naylor RJ, Nohria V. Climbing behaviour induced by apomorphine in mice: a potential model for the detection of neuroleptic activity. Eur J Pharmacol 1978;50:39–50.10.1016/0014-2999(78)90251-0Search in Google Scholar
42. Protais P, Costentin J, Schwartz JC. Climbing behavior induced by apomorphine in mice: a simple test for the study of dopamine receptors in striatum. Psychopharmacology 1976;50:1–6.10.1007/BF00634146Search in Google Scholar PubMed
43. Bardin L, Kleven MS, Barret-Grevoz C, Depoortere R, Newman-Tancredi A. antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties. Neuropsychopharmacology 2005;31:1869–79.10.1038/sj.npp.1300940Search in Google Scholar PubMed
44. Pandy V, Narasingam M, Mohamed Z. Antipsychotic-like activity of Noni (Morinda citrifolia Linn.) in mice. BMC Complement Altern Med 2012;12:1–9.10.1186/1472-6882-12-186Search in Google Scholar PubMed PubMed Central
45. Amos S, Binda L, Chindo BA, Tseja A, Odutola AA, Wambebe C, et al. Neuropharmacological effects of hibiscus sabdariffa aqueous extract. Pharm Biol 2003;41:325–29.10.1076/phbi.41.5.325.15933Search in Google Scholar
46. Oyemitan IA, Olayera OA, Alabi A, Abass LA, Elusiyan CA, Oyedeji AO, et al. Psychoneuropharmacological activities and chemical composition of essential oil of fresh fruits of Piper guineense (Piperaceae) in mice. J Ethnopharmacol 2015;166:240–49.10.1016/j.jep.2015.03.004Search in Google Scholar PubMed
47. Sanberg PR. Haloperidol-induced catalepsy is mediated by postsynaptic dopamine receptors. Nature 1980;284:472–73.10.1038/284472a0Search in Google Scholar PubMed
48. Shopsin B, Klein H, Aaronsom M, Collora M. Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients: a controlled, double-blind comparison. Arch Gen Psychiatry 1979;36:657–64.10.1001/archpsyc.1979.01780060047005Search in Google Scholar PubMed
49. González-Lugo OE, Ceballos-Huerta F, Jiménez-Capdeville ME, Arankowsky-Sandoval G, Góngora-Alfaro JL. Synergism of theophylline and anticholinergics to inhibit haloperidol-induced catalepsy: a potential treatment for extrapyramidal syndromes. Prog Neuro-Psychopharmacol Biol Psychiatry 2010;34:1465–71.10.1016/j.pnpbp.2010.08.003Search in Google Scholar PubMed
50. Klemm W. Evidence for a cholinergic role in haloperidol-induced catalepsy. Psychopharmacology 1985;85:139–42.10.1007/BF00428402Search in Google Scholar PubMed
51. Neal-Beliveau BS, Joyce JN, Lucki I. Serotonergic involvement in haloperidol–induced catalepsy. J Pharmacol Exp Ther 1993;265:207–17.10.1016/S0022-3565(25)38100-0Search in Google Scholar
52. Surmeier DJ, Ding J, Day M, Wang Z, Shen W. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci 2007;30: 228–35.10.1016/j.tins.2007.03.008Search in Google Scholar PubMed
53. Baiocchi C, Medana C, Giancotti V, Aigotti R, Dal Bello F, Massolino C, et al. Qualitative characterization of Desmodium adscendens constituents by high-performance liquid chromatography-diode array ultraviolet-electrospray ionization multistage mass spectrometry. Eur J Mass Spectrom 2013;19:1–15.10.1255/ejms.1214Search in Google Scholar PubMed
54. Addy ME. Several chromatographically distinct fractions of Desmodium adscendens inhibit smooth muscle contractions. Int J Crude Drug Res 1989;27:81–91.10.3109/13880208909053942Search in Google Scholar
55. McManus OB, Harris GH, Giangiacomo KM, Feigenbaum P, Reuben JP, Addy ME, et al. An activator of calcium-dependent potassium channels isolated from a medicinal herb. Biochemistry 1993;32:6128–33.10.1021/bi00075a002Search in Google Scholar PubMed
56. Sonibare MA, Umukoro S, Shonibare ET. Antipsychotic property of aqueous and ethanolic extracts of Lonchocarpus cyanescens (Schumach and Thonn.) Benth. (Fabaceae) in rodents. J Nat Med 2012;66:127–32.10.1007/s11418-011-0562-6Search 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