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Drug Res (Stuttg) 2014; 64(7): 368-376
DOI: 10.1055/s-0033-1358712
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Antidepressant and Anxiolytic Properties of the Methanolic Extract of Momordica charantia Linn (Cucurbitaceae) and its Mechanism of Action

I. O. Ishola
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
,
A. A. Akinyede
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
,
A. M. Sholarin
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
› Author Affiliations
Further Information

Publication History

received 21 June 2013

accepted 21 October 2013

Publication Date:
13 November 2013 (online)

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Abstract

Background:

The whole plant of Momordica charantia Linn (Cucurbitaceae) is used in traditional African medicine in the management of depressive illness.

Methods:

Momordica charantia (MC) (50–400 mg/kg, p.o.) was administered 1 h before behavioural studies using the forced swimming test (FST) and tail suspension test (TST) to investigate antidepressant-like effect while the anxiolytic-like effect was evaluated with elevated plus maze test (EPM), hole-board test (HBT), and light-dark test (LDT).

Results:

Acute treatment with MC (50–400mg/kg) significantly increased swimming time (86.51%) and reduced the duration of immobility (52.35%) in FST and TST with peak effects observed at 200 mg/kg, respectively, in comparison to control. The pretreatment of mice with either sulpiride (dopamine D2 receptor antagonist), or metergoline (5-HT2 receptor antagonist), or cyproheptadine (5-HT2 receptor antagonist), or prazosin (α1-adrenoceptor antagonist), or yohimbine (α2-adrenoceptor antagonist), and atropine (muscarinic cholinergic receptor antagonist) 15 min before oral administration of MC (200 mg/kg) significantly blocked its anti-immobility effect. Similarly, MC (200 mg/kg) significantly reduced anxiety by increasing the open arm exploration (64.27%) in EPM, number of head-dips in HBT (34.38%), and time spent in light compartment (29.38%) in the LDT. However, pretreatment with flumazenil (GABAA receptor antagonist) 15 min before MC (200 mg/kg) significantly blocked (54.76%) its anxiolytic effect.

Conclusion:

The findings in this study showed that MC possesses antidepressant-like effect that is dependent on the serotonergic (5-HT2 receptor), noradrenergic (α1- and α2-adrenoceptors), dopaminergic (D2 receptor), and muscarinic cholinergic systems and an anxiolytic-like effect that might involve an action on benzodiazepine-type receptor.

Key words

dopaminergic - GABAergic - ionotropic - noradrenergic - serotonergic
 

  • References

  • 1 Mora S, Dıaz-Veliz G, Millan R et al. Anxiolytic and antidepressant-like effects of the hydroalcoholic extract from Aloysia polystachya in rats. Pharmacol Biochem Behav 2005; 82: 373-378
    CrossrefPubMedSearch in Google Scholar
  • 2 Dilsaver SC. Cholinergic mechanisms in depression. Brain Res 1986; 396: 285-316
    PubMedSearch in Google Scholar
  • 3 Ressler KJ, Nemeroff CB. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depression and anxiety 2000; 12: 12-19
    PubMedSearch in Google Scholar
  • 4 Johnson MR, Lydiard RB, Ballenger JC. Panic disorder: Pathophysiology and drug treatment. Drugs 1995; 49: 328-344
    CrossrefPubMedSearch in Google Scholar
  • 5 Zhang Z. Therapeutic effects of herbal extracts and constituents in animal models of psychiatric disorders. Life Sci 2004; 75: 1659-1699
    CrossrefPubMedSearch in Google Scholar
  • 6 Lans C, Brown G. Observations on ethnoveterinary medicines in Trinidad and Tobago. Preventive Vet Med 1998; 35: 125-142
    CrossrefPubMedSearch in Google Scholar
  • 7 Grover JK, Yadav SP. Pharmacological actions and potential uses of Momordica charantia: A review. J Ethnopharmacol 2004; 93: 123-132
    CrossrefPubMedSearch in Google Scholar
  • 8 Ganesan A, Subramanian Natesan S, Perumal P et al. Anxiolytic, antidepressant and anti-Inflammatory activities of methanol extract of Momordica Charantia Linn Leaves (Cucurbitaceae). Iranian J Pharmacol Ther 2008; 7: 43-47
    PubMedSearch in Google Scholar
  • 9 Odugbemi TO. Outlines and Pictures of Medicinal Plants from Nigeria. University of Lagos Press; Lagos, Nigeria: 2006
    Search in Google Scholar
  • 10 Ojewole JA, Adewole SO, Olayiwola G. Hypoglycaemic and hypotensive effects of Cucurbitaceae whole-plant aqueous extract in rats. Cardiovasc J S Afr 2006; 17: 227-232
    PubMedSearch in Google Scholar
  • 11 Malik ZA, Singh M, Sharma PL. Neuroprotective effect of Momordica charantia in global cerebral ischemia and reperfusion induced neuronal damage in diabetic mice. J Ethnopharmacol 2011; 133: 729-734
    CrossrefPubMedSearch in Google Scholar
  • 12 Raman A, Lau C. Anti-diabetic properties and phytochemistry of Momordica charantia L. (Cucurbitaceae). Phytomedicines 1996; 2: 349-362
    PubMedSearch in Google Scholar
  • 13 NIH. Guide for the Use of Laboratory Animals DHHS, PHS. NIH Publication No. 85-23 (1985 Revised)
    PubMed
  • 14 Brown RE, Corey SC, Moore AK. Differences in measures of exploration and fear in MHC-congenic C57BL/6J and B6-H-2K mice. Behav Genetics 1999; 26: 263-271
    PubMedSearch in Google Scholar
  • 15 Porsolt RD, Bertin A, Jalfre M. Behavioural despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977; 229: 327-336
    PubMedSearch in Google Scholar
  • 16 Ulak G, Muttu O, Tanyen P et al. Involvement of serotonin receptor subtypes in the antidepressant – like effect of trim in the rat forced swimming test. Pharmacol Biochem Behav 2010; 95: 308-314
    CrossrefPubMedSearch in Google Scholar
  • 17 Stachowicz K, Chojnacka-Wojcik E, Kłak K et al. Anxiolytic-like effect of group III mGlu receptor antagonist is serotonin-dependent. Neuropharmacol 2007; 52: 306-312
    CrossrefPubMedSearch in Google Scholar
  • 18 Gu L, Liu Y, Wang Y et al. Role for monoaminergic systems in the antidepressant-like effect of ethanol extracts from Hemerocallis citrina. J Ethnopharmacol 2012; 139: 780-787
    CrossrefPubMedSearch in Google Scholar
  • 19 Liebenberg N, Wegener G, Harvey BH et al. Investigating the role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonism. Behav Brain Res 2010; 209: 137-141
    CrossrefPubMedSearch in Google Scholar
  • 20 Steru L, Chermat R, Thierry B et al. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacol 1985; 85: 367-370
    CrossrefPubMedSearch in Google Scholar
  • 21 Moreira EG, Nascimento N, Rogero JR et al. Gabaergic benzodiazepine system is involved in the crotoxin-induced anxiogenic effect. Pharmacol Biochem Behav 2000; 65: 7-13
    CrossrefPubMedSearch in Google Scholar
  • 22 Braida D, Limonta V, Capurro V et al. Involvement of kappa-opioid and endocannabinoid system on salvinorin A-induced reward. Biol Psychiatry 2008; 63: 286-292
    CrossrefPubMedSearch in Google Scholar
  • 23 Lister RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacol 1987; 92: 180-185
    PubMedSearch in Google Scholar
  • 24 Young R, Johnson DN. A fully automated light/dark apparatus useful for comparing anxiolytic agents. Pharmacol Biochem Behav 1991; 40: 739-743
    CrossrefPubMedSearch in Google Scholar
  • 25 Nogueira E, Vassilieff VS. Hypnotic, anticonvulsant and muscle relaxant effects of Rubus brasiliensis. Involvement of GABAA-system. J Ethnopharmacol 2000; 70: 275-280
    CrossrefPubMedSearch in Google Scholar
  • 26 Belozertseva IV, Kos T, Popik P et al. Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests. Eur Neuropsychopharmacol 2007; 17: 172-179
    CrossrefPubMedSearch in Google Scholar
  • 27 Ishola IO, Chatterjee M, Tota S et al. Antidepressant and anxiolytic effects of amentoflavone isolated from Cnestis ferruginea in mice. Pharmacol Biochem Behav 2012; 103: 322-331
    CrossrefPubMedSearch in Google Scholar
  • 28 Ali-Kodja F, Bougard M, Perrault G et al. Effect of serotonin uptake inhibitors on the immobility of mice in the tail suspension test. Br J Pharmacol 1986; 87: 130P
    PubMedSearch in Google Scholar
  • 29 Detke MJ, Rickels M, Lucki I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacol 1995; 121: 66-72
    CrossrefPubMedSearch in Google Scholar
  • 30 Redrobe JP, Bourin M. Clonidine potentiates the effects of 5-HT, 5-HT2A/2C and 5-HT1A/1B antagonists and 8-OH-DPAT in the mouse forced swimming test. EurNeuropsychopharmacol 1998; 8: 169-173
    PubMedSearch in Google Scholar
  • 31 Mineur YS, Obayemi A, Wigestrand MB et al. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior. Proc Natl Acad Sci USA 2013; 110: 3573-3578
    CrossrefPubMedSearch in Google Scholar
  • 32 Drevets WC, Zarate Jr CA, Furey ML. Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: A review. Biol Psychiatry 2013; 73: 1156-1163
    CrossrefPubMedSearch in Google Scholar
  • 33 Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacol 1999; 38: 1083-1152
    CrossrefPubMedSearch in Google Scholar
  • 34 D’Aquila PS, Collu M, Gessa GL et al. The role of dopamine in the mechanism of action of antidepressant drugs. Eur J Pharmacol 2000; 405: 365-373
    CrossrefPubMedSearch in Google Scholar
  • 35 Skolnicka P, Popikb P, Janowskyc A et al. Antidepressant-like actions of DOV 21,947: a “triple” reuptake inhibitor. Eur J Pharmacol 2003; 461: 99-104
    CrossrefPubMedSearch in Google Scholar
  • 36 McLean A, Rubinsztein JS, Robbins TW et al. The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression. Psychopharmacol (Berlin) 2004; 171: 286-297
    CrossrefPubMedSearch in Google Scholar
  • 37 Mitani H, Shirayama Y, Yamada T et al. Plasma levels of homovanillic acid, 5-hydroxyindoleacetic acid and cortisol, and serotonin turnover in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 531-534
    CrossrefPubMedSearch in Google Scholar
  • 38 An L, Zhang Y, Yu N et al. Role for serotonin in the antidepressant-like effect of a flavonoid extract of Xiaobuxin-Tang. Pharmacol Biochem Behav 2008; 89: 572-580
    CrossrefPubMedSearch in Google Scholar
  • 39 Danysz W, Kostowski W, Kozak W et al. On the role of noradrenergic neurotransmission in the action of desipramine and amitriptylline in animal models of depression. Pol J Pharmacol Pharm 1986; 38: 285-298
    PubMedSearch in Google Scholar
  • 40 Schramm NL, McDonald MP, Limbird LE. The alpha(2a)-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety. J Neurosci 2001; 21: 4875-4882
    PubMedSearch in Google Scholar
  • 41 Pandey SC, Ren X, Sagen J et al. Beta-adrenergic receptor subtypes in stress-induced behavioral depression. Pharmacol Biochem Behav 1995; 51: 339-344
    CrossrefPubMedSearch in Google Scholar
  • 42 Sheline YI. Neuroimaging studies of mood disorder effects on the brain. Biol Psychiatry 2003; 54: 338-352
    CrossrefPubMedSearch in Google Scholar
  • 43 Fujishiro J, Imanishi T, Onozawa K et al. Comparison of the anticholinergic effects of the serotonergic antidepressants, paroxetine, fluvoxamine and clomipramine. Eur J Pharmacol 2002; 454: 183-188
    CrossrefPubMedSearch in Google Scholar
  • 44 File S, Lister R, Nutt D. The anxiogenic action of benzodiazepine antagonists. Neuropharmacol 1982; 21: 1033-1037
    CrossrefPubMedSearch in Google Scholar
  • 45 Makanjuola ROA, Hill G, Dow RC et al. The effects of psychotropics drugs on exploratory and stereotyped behavior of rats studied on a hole-board. Psychopharmacol 1977; 55: 67-74
    CrossrefPubMedSearch in Google Scholar
  • 46 Barrett JE. Animal behavior models in the analysis and understanding of anxiolytic drugs acting at serotonin receptors. In: Olivier B, Mos J, Slangen JL . (eds.). Animal models in psychopharmacology. Basel’ Birkhauser Verlag; 1991: 37-52
    CrossrefSearch in Google Scholar
  • 47 Herrera-Ruiz M, Jimenez-Ferrer JE, De Lima TCM et al. Anxiolytic and antidepressant-like activity of a standardized extract from Galphimia glauca. Phytomedicine 2005; 13: 23-28
    PubMedSearch in Google Scholar
  • 48 Brinkhaus B, Lindner M, Schuppan D et al. Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica. Phytomedicine 2000; 7: 427-448
    CrossrefPubMedSearch in Google Scholar
  • 49 Wijeweera P, Arnason JT, Koszycki D et al. Evaluation of anxiolytic properties of Gotukola (Centella asiatica) extracts and asiaticoside in rat behavioral models. Phytomedicine 2006; 13: 668-676
    CrossrefPubMedSearch in Google Scholar
  • 50 Blanchard DC, Griebel G, Blanchard RJ. Mouse defensive behaviors: Pharmacological and behavioral assays for anxiety and panic. Neurosci Biobehav Rev 2001; 25: 205-218
    CrossrefPubMedSearch in Google Scholar
  • 51 Espejo EF. Effects of weekly or daily exposure to the elevated plus-maze in male mice. Behav Brain Res 1997; 87: 233-238
    CrossrefPubMedSearch in Google Scholar
  • 52 Ansari NM, Houlihan L, Hussain B et al. Antioxidant activity of five vegetables traditionally consumed by South-Asian migrants in Bradford, Yorkshire, UK. Phytotherapy Res 2005; 19: 907-911
    CrossrefPubMedSearch in Google Scholar
  • 53 Chandra A, Mahdi A, Singh RK et al. Effect of Indian herbal hypoglycemic agents on antioxidant capacity and trace elements content in diabetic rats. J Med Food 2008; 11: 506-512
    CrossrefPubMedSearch in Google Scholar