Background: Mangifera indica (Anacardiaceae) is an important herb in the traditional African and Ayurvedic medicines. The stem barks are used in the treatment of hypertension, insomnia, tumour, depression, rheumatism and as a tonic. This study was carried out to investigate antidepressant- and anxiolytic-like effect of the hydroethanol stem bark extract of M. indica (HeMI) in mice.
Methods: HeMI (12.5–100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM).
Results: HeMI (12.5–100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, p<0.001], [F(6,56)=7.55, p<0.001] in the FST and TST, respectively. Moreover, co-administration of sub-therapeutic doses of imipramine or fluoxetine with HeMI (3.125 mg/kg) elicited significant reduction in time spent immobile in the FST. However, pretreatment of mice with parachlorophenylalanine, metergoline, yohimbine or sulpiride abolished the antidepressant-like effect elicited by HeMI. In the EPM, HeMI produced significant [F(5,42)=8.91, p<0.001] increase in open arms exploration by 75.55 % and this effect was blocked by pretreatment of mice with flumazenil or metergoline.
Conclusions: Findings from this study showed antidepressant-like effect of M. indica through interaction with 5-HT2 receptor, α2-adrenoceptor and dopamine D2-receptors. Also, an anxiolytic-like effect through its affinity for 5-HT2 and benzodiazepine receptors. Hence, M. indica could be a potential phytotherapeutic agent in the treatment of mixed anxiety-depressive illness.
1. Elliott JM, Heal DJ, Marsden CA. Experimental approaches to anxiety and depression. Chichester: John Wiley & Sons, Ltd. Ed, 1992.
2. Kessler RC. The global burden of anxiety and mood disorders: putting the European study of the epidemiology of mental disorders (ESEMeD) findings into perspective. J Clin Psychiatry 2007;68(Suppl. 2):10–19.
3. Buller R, Legrand V. Novel treatments for anxiety and depression: hurdles in bringing them to the market. Drug Discov Today 2001;6(23):1220–30.
4. Cryan JF, Sweeney FF. The age of anxiety: role of animal models of anxiolytic action in drug discovery. Br J Pharmacol 2011;164:1129–61.
5. Burkill HM. The useful plants of west tropical Africa, 2nd ed. Vol. 4. Families M-R. Richmond: Royal Botanic Gardens, Kew, 1997.
6. Odugbemi TO. Outlines and pictures of medicinal plants from Nigeria. Lagos, Nigeria: University of Lagos Press, 2006.
7. Shah KA, Patel MB, Patel RJ. Mangifera indica (mango). Pharmacog Rev 2010;4:42–8.
8. Makare N, Bodhankar S, Rangari V. Immunomodulatory activity of alcoholic extract of Mangifera indica L. in mice. J. Ethnopharmacol 2001;78:133–7.
9. Garcia D, Escalante M, Delgado R, Ubeira FM, Leiro J. Anthelminthic and antiallergic activities of Mangifera indica L. stem bark components Vimang and mangiferin. Phytother Res 2003;17:1203–8.
10. Ojewole JA. Antiinflammatory, analgesic and hypoglycemic effects of Mangifera indica Linn. (Anacardiaceae) stem–bark aqueous extract. Methods Find Exp Clin. Pharmacol 2005;27:547–54.
11. Zajac D, Stasinska A, Delgado R, Pokorski M. Mangiferin and its traversal into the brain. Adv Exp Med Biol 2013;756:105–11.
12. Sanchez GM, Rodríguez HMA, Giuliani A, Núñez Sellés AJ, Rodríguez NP, León Fernández OS, et al. Protective effect of Mangifera indica L. extract (Vimang) on the injury associated with hepatic ischaemia reperfusion. Phytother Res 2003;17:197–201.
13. Sanchez GM, Re L, Giuliani A, Nunez-Selles AJ, Davison GP, Leon-Fernandez OS. Protective effects of Mangifera indica L. extract, mangiferin and selected antioxidants against TPA-induced biomolecules oxidation and peritoneal macrophage activation in mice. Pharmacol Res 2000;42:565–73.
14. Barreto JC, Trevisan MT, Hull WE, Erben G, de Brito ES, Pfundstein B, et al. Characterization and quantitation of polyphenolic compounds in bark, kernel, leaves, and peel of mango (Mangifera indica L.). J Agric Food Chem 2008;56:5599–610.
15. Garrido-Suárez BB, Garrido G, García ME, Delgado-Hernández R. Antihyperalgesic effects of an aqueous stem bark extract of Mangifera indica L.: role of mangiferin isolated from the extract. Phytother Res 2014;28(11):1646–53.
16. Guha S, Ghosal S, Chattopadhyay U. Antitumor, immunomodulatory and anti-HIV effect of mangiferin, a naturally occurring glucosylxanthone. Chemotherapy 1996;42:443–51.
17. Biradar SM, Joshi H, Chheda TK. Neuropharmacological effect of mangiferin on brain cholinesterase and brain biogenic amines in the management of Alzheimer’s disease. Eur J Pharmacol 2012;683:140–7.
18. Edeoga HO, Okwu DE, Mbaebie BO. Phytochemical constituents of some Nigerian medicinal plants. Afr J Biotechnol 2005;4:685–8.
19. NIH. Guide for the care and use of laboratory animals, 8th ed. Washington, DC: National Academies Press, 2011:37–66.
20. The Organisation of Economic Co-operation and Development (OECD). The OECD guideline for testing of chemical: 420 acute oral toxicity. Paris: OECD, 2001:1–14.
21. Bijak M, Papp M. The effect of chronic treatment with imipramine on the responsiveness of hippocampal CA1 neurons to phenylephrine and serotonin in a chronic mild stress model of depression. Eur Neuropsychopharmacol 1995;5:43–8.
22. Pacher P, Kecskemeti V. Trends in the development of new antidepressants. Is there a light at the end of the tunnel? Curr Med Chem 2004;11:925–43.
23. Porsolt RD, Bertin A, Jalfre M. Behavioural despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977;229:327–36.
24. Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacol 1985;85:367–70.
25. Ishola IO, Akinyede AA, Sholarin AM. Antidepressant and anxiolytic properties of the methanolic extract of Momordica charantia Linn (Cucurbitaceae) and its mechanism of action. Drug Res (Stuttg) 2014;64:368–76.
26. O‘Leary OF, Bechtholt AJ, Crowley JJ, Hill TE, Page ME, Lucki I. Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test. Psychopharmacology (Berl) 2007;192:357–71.
27. Przegaliński E, Moryl E, Papp M. The effect of 5-HT1A receptor ligands in a chronic mild stress model of depression. Neuropharmacol 1995;34:1305–10.
28. Machado DG, Bettio LE, Cunha MP, Santos AR, Pizzolatti MG, Brighente IM, et al. Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems. Eur J. Pharmacol 2008;587:163–8.
29. Tanyeri P, Buyukokuroglu ME, Mutlu O, Ulak G, Yıldız AF, Komsuoglu CI, et al. Involvement of serotonin receptor subtypes in the antidepressant-like effect of beta receptor agonist Amibegron (SR 58611A): an experimental study. Pharmacol Biochem Behav 2013;105:12–16.
30. Gu L, Liu Y, Wang Y, Yi L. Role for monoaminergic systems in the antidepressant-like effect of ethanol extracts from Hemerocallis citrina. J Ethnopharmacol 2012;139:780–7.
31. Braida D, Capurro V, Zani A, Rubino T, Viganò D, Parolaro D, et al. Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents. Br J Pharmacol 2009;157:844–53.
32. Lister RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacol 1987;92:180–5.
33. Ishola IO, Chatterjee M, Tota S, Narender T, Adeyemi OO, Palit G, et al. Antidepressant and anxiolytic effects of amentoflavone isolated from Cnestis ferruginea in mice. Pharmacol Biochem Behav 2012;103:322–31.
34. Cryan JF, Mombereau C, Vassou A. The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 2005;29:571–625.
35. Porsolt RD. Animal models of depression: utility for transgenic research. Rev Neurosci 2000;11:53–8.
36. Cryan JF, Markou A, Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trend Pharmacol Sci 2002;23:238–45.
37. Thierry B, Steru L, Chermat R, Simon P. Searching-waiting strategy: a candidate for an evolutionary model of depression? Behav Neural Biol 1984;41:180–9.
38. Lucki I. A prescription to resist proscriptions for murine models of depression. Psychopharmacol (Berl) 2001;153:395–8.
39. Artigas F. Serotonin receptors involved in antidepressant effects. Pharmacol Ther 2013;137:119–31.
40. Cervo L, Grignaschi G, Rossi C, Samanin R. Role of central serotonergic neurons in the effect of sertraline in rats in the forced swim test. Eur J Pharmacol 1991;196:217–22.
41. Brunello N, Blier P, Judd LL, Mendlewicz J, Nelson CJ, Souery D, et al. Noradrenaline in mood and anxiety disorders: basic and clinical studies. Int Clin Psychopharmacol 2003;18:191–202.
42. Bortolozzi A, Artigas F. Control of 5-hydroxytryptamine release in the dorsal raphe nucleus by the noradrenergic system in rat brain. Role of alpha-adrenoceptors. Neuropsychopharmacol 2003;28:421–34.
43. Pudovkina OL, Cremers TI, Westerink BH. Regulation of the release of serotonin in the dorsal raphe nucleus by alpha1 and alpha2 adrenoceptors. Synapse 2003;50:77–82.
44. Stein M. Depression, anhedonia, and psychomotor symptoms: the role of dopaminergic neurocircuitry. CNS Spectr 2008;13:7.
45. Klimke A, Larisch R, Janz A, Vosberg H, Müller-Gärtner HW, Gaebel W. Dopamine D2 receptor binding before and after treatment of major depression measured by [123I]IBZM SPECT. Psychiatry Res 1999;90:91–101.
46. Nutt DJ. The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 2006;67:3–8.
47. Meyer JH, McNeely HE, Sagrati S, et al. Elevated putamen D(2) receptor binding potential in major depression with motor retardation: an [11C]raclopride positron emission tomography study. Am J Psychiatry 2006;163:1594–602.
48. Rickels K, Downing R, Schweizer E, Hassman H. Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry 1993;50:884.
49. Smith VM, Iannatonne S, Achal S, Jeffers RT, Antle MC. The serotonergic anxiolytic buspirone attenuates circadian responses to light. Eur J Neurosci 2014;40(10):3512–25.
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