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Drug Res (Stuttg) 2015; 65(09): 490-494
DOI: 10.1055/s-0034-1389920
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Antidepressant Effect of Thymoquinone in Animal Models of Depression

M. Aquib
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
,
A. K. Najmi
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
,
M. Akhtar
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
› Author Affiliations
Further Information

Publication History

received 05 June 2014

accepted 21 August 2014

Publication Date:
10 September 2014 (online)

Also available at
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Abstract

Objective: The present study was carried out to determine the role of thymoquinone (TQ) in modulating the levels of neurotransmitter and reducing the oxidative stress in animal models of depression.

Material and Methods: Mice were divided into 5 groups, each group had 6 animals. TQ (20 mg/kg) in corn oil and fluoxetine (10 mg/kg) in normal saline were administered intraperitoneally (i.p.) half an hour before performing behavioural tests. Modified forced swim test (MFST) and tail suspension test (TST) were used to assess the antidepressant effect in mice. Animals were sacrificed and their brains were removed for biochemical estimation after performing behavioural tests.

Results: TQ treatment showed increased swimming, climbing and decreased immobility times in MFST and TST. Combination of TQ with fluoxetine in MFST and TST showed potentiating effect in the present study. A significant elevation of 5-hydroxytryptamine (5-HT) levels was observed following TQ administration in the behavioural models studied. MFST and TST reduced glutathione and elevated TBARS levels in mice. Pre-treatment of TQ restored glutathione and decreased TBARS levels. TQ combination with fluoxetine also showed reduction of TBARS and increased glutathione levels.

Conclusion: TQ demonstrated antidepressant effects in MFST and TST respectively in the present study. It further demonstrated antioxidant effects by reducing thiobarbituric acid reactive substance (TBARS) and increasing reduced glutathione (GSH) levels. Although our results are preliminary, further investigations may be required however, based on afore mentioned results, it may be suggested that TQ could be a potential candidate for the management of depression.

Key words

depression - thymoquinone - modified FST - TST
 

  • References

  • 1 Nemeroff CB. The burden of severe depression: a review of diagnostic challenges and treatment alternatives. J Psychiat Res 2007; 41: 189-206
    CrossrefPubMedGoogle Scholar
  • 2 Kessler RC, Berglund P, Demler O et al. National co morbidity survey replication, The epidemiology of major depressive disorder: results from the national co morbidity survey replication (NCS-R). JAMA 2003; 289: 3095-3105
    CrossrefPubMedGoogle Scholar
  • 3 Le’pine JP, Briley M. The increasing burden of depression. Neuropsychiatric Disease Treatment 2004; 7: 3-7
    PubMedGoogle Scholar
  • 4 Dumas RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997; 54: 597-606
    CrossrefPubMedGoogle Scholar
  • 5 Vander AJ. The effects of tryptophan depletion on mood and psychiatric symptoms. J Affective Disorders 2007; 64: 107-119
    PubMedGoogle Scholar
  • 6 Nestler EJ, Barrot M, DiLeone RJ et al. Neurobiology of depression. Neuron 2002; 34: 3413-3425
    PubMedGoogle Scholar
  • 7 Rush AJ, Trivedi M, Fava M. Depression, IV: STAR*D treatment trial for depression. Am J Psychiatry 2003; 160: 237
    CrossrefPubMedGoogle Scholar
  • 8 McEwen BS, Magarinos AM. Stress and hippocampal plasticity: implications for the pathophysiology of affective disorders. Hum Psychopharmacol 2001; 16: S7-S19
    CrossrefPubMedGoogle Scholar
  • 9 Kessler RC, Soukup J, Davis RB et al. The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psych 2001; 158: 289-294
    CrossrefPubMedGoogle Scholar
  • 10 Wong ML, Licinio J. Research and treatment approaches to depression. Nat Rev Neurosci 2001; 2: 343-351
    CrossrefPubMedGoogle Scholar
  • 11 Tachil AF, Mohan R, Bhugra D. The evidence base of complementary and alternative therapies in depression. J Affective Disorders 2007; 97: 23-35
    CrossrefPubMedGoogle Scholar
  • 12 Salma C, Rouhou S, Besbes B et al. Nigella sativa L.: Chemical composition and physicochemical characteristics of lipid fraction. Food Chemistry 2006; 2-9
    PubMedGoogle Scholar
  • 13 Ghannadi A, Hajhashemi V, Jafarabadi H. An investigation of the analgesic and anti-inflammatory effects of Nigella sativa seed polyphenols. J Med Food 2005; 4: 488-493
    PubMedGoogle Scholar
  • 14 Houghton PJ, Zarka R, de lass Herass B et al. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med 1995; 61: 33-36
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Hosseinzadeh H, Parvardeh S, Asl MN et al. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine 2007; 14: 621-627
    CrossrefPubMedGoogle Scholar
  • 16 Abdel-Fattah AM, Matsumoto K, Watanabe H. Anti-nociceptive effects of Nigella sativa oil and its major component, thymoquinone in mice. Eur J Pharmacol 2000; 400: 89-97
    CrossrefPubMedGoogle Scholar
  • 17 Iddamaldeniya SS, Thabrew MI, Wickramasinghe SM et al. A long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra. J Carcinog 2006; 5: 11-16
    CrossrefPubMedGoogle Scholar
  • 18 Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine 2004; 11: 56-64
    CrossrefPubMedGoogle Scholar
  • 19 Gilhotra N, Dhingra D. Thymoquinone produced anti-anxiety-like effects in mice through modulation of GABA and NO levels. Pharmacological Reports 2011; 63: 660-670
    CrossrefPubMedGoogle Scholar
  • 20 Kanter M. Effects of Nigella sativa and its major constituents, thymoquinone on sciatic nerves in experimental diabetic neuropathy. Neurochem Res 2008; 33: 87-96
    CrossrefPubMedGoogle Scholar
  • 21 Alhamdan AA. Neuroprotective effect of thymoquinone on repeated immobilization stress-induced oxidative stress in rats. Asian J Med Sci 2013; 64: 83-91
    PubMedGoogle Scholar
  • 22 Perveen T, Haider S, Kanwal S et al. Repeated administration of Nigella sativa increases 5-HT turnover and produces anxiolytic effect in rat. Pak J Pharm Sci 2009; 29: 139-144
    PubMedGoogle Scholar
  • 23 Schildkraut JJ, Kety SS. Biogenic amines and emotion. Science 1967; 156: 21-37
    CrossrefPubMedGoogle Scholar
  • 24 Maes M, Yirmyia R, Noraberg J et al. The inflammatory and neurodegenerative hypothesis of depression: Leads for future research and new drug developments in depression. Metab Brain Dis 2009; 24: 27-53
    CrossrefPubMedGoogle Scholar
  • 25 Sarandol A, Sarandol E, Eker SS et al. Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative anti-oxidative systems. Hum Psychopharmacol 2007; 22: 67-73
    CrossrefPubMedGoogle Scholar
  • 26 Forlenza MJ, Miller GE. Increased serum levels of 8-hydroxy-2′-deoxy guanosine in clinical depression. Psychosom Med 2006; 68: 1-7
    PubMedGoogle Scholar
  • 27 Porsolt RD. Depression: a new animal model sensitive to antidepressant treatments. Nature 1977; 266: 730-732
    CrossrefPubMedGoogle Scholar
  • 28 Steru L, Chermat R, Thierry B et al. The automated tail suspension test: a computerized device which differentiates psychotropic drugs. Prog Neuropsychopharmacol Biol Psychiatry 1987; 11: 659-671
    PubMedGoogle Scholar
  • 29 Brown GW. Onset and course of depressive disorders. Summary of a research programme 1996; 23: 625-630
    PubMedGoogle Scholar
  • 30 Pong K. Oxidative stress in neurodegenerative diseases: therapeutic implications for superoxide dismutase mimetic. Exp Opin Biol Ther 2003; 3: 127-139
    CrossrefPubMedGoogle Scholar
  • 31 Cryan JF, Page ME, Lucki I. Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test. Eur J Pharmacol 2002; 436: 197-205
    CrossrefPubMedGoogle Scholar
  • 32 Akhtar M, Pillai KK, Vohora D. Effect of thioperamide on modified forced swimming test-induced oxidative stress in mice. Basic Clinical Pharmacol Toxicol 2005; 97: 218-221
    PubMedGoogle Scholar
  • 33 Ripoll N, Denis J, Paul D et al. Antidepressant-like effects in various mice strains in the tail suspension test. J Neu Bio Rev 2003; 143: 193-200
    PubMedGoogle Scholar
  • 34 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
    CrossrefPubMedGoogle Scholar
  • 35 Ellman GL. Tissue sulfhydryl group. Arch Biochem Biophys 1957; 82: 70-77
    PubMedGoogle Scholar
  • 36 Sedlak J, Lindsay RH. Estimation of total protein bound and non protein sulfhydryl group in tissue with Ellman’s reagent. Anal Biochem 1968; 25: 192-220
    CrossrefPubMedGoogle Scholar
  • 37 Curzon G, Green AR. Rapid method for the determination of 5-hydroxy tryptamine and 5-hydroxy indole acetic acid in small regions of rat brain. Life Sci Oxford 1968; 7: 653-655
    CrossrefPubMedGoogle Scholar
  • 38 Lowery OH, Rosenbrough NJ, Farr AL et al. Protein measurement with Folin phenol reagent. J Bio Chem 1951; 193: 265-275
    PubMedGoogle Scholar
  • 39 Borsini F. Role of the serotonergic system in the forced swimming test. Neurosci Biobehav Rev 1995; 19: 377-395
    CrossrefPubMedGoogle Scholar
  • 40 Lucki I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. J Neu Bio Rev 1997; 8: 523-532
    PubMedGoogle Scholar
  • 41 Madrigal JL, Moro MA, Lizasoain I et al. Stress-induced increase in extracellular sucrose space in rats is mediated by nitric oxide. Brain Res 2002; 938: 87-91
    CrossrefPubMedGoogle Scholar
  • 42 Baek BS, Kwon HJ, Lee KH et al. Regional difference of ROS generation, lipid peroxidation and antioxidant enzyme activity in rat brain and their dietary modulation. Arch Pharm Res 1999; 22: 361-366
    CrossrefPubMedGoogle Scholar
  • 43 Akhtar M, Maikiyo AM, Khanam R et al. Ameliorating effect of two extracts of Nigella sativa on middle cerebral artery occluded rats. J Pharm Bio Allied Sciences 2012; 4: 70-75
    PubMedGoogle Scholar
  • 44 Akhtar M, Maikiyo AM, Najmi AK et al. Neuroprotective effects of chloroform and petroleum ether extracts of Nigella sativa seeds in cerebral ischemia. J Pharm Bio Allied Sciences 2013; 5: 119-125
    PubMedGoogle Scholar
  • 45 Floyd RA, Carney JM. Free radical damage to protein and DNA: mechanism involved and relevant observation on brain undergoing oxidative stress. Ann Neurol 1992; 32: S22-S27
    CrossrefPubMedGoogle Scholar
  • 46 Zaidi SM, Banu N. Antioxidant potential of vitamin A, E and C in modulating oxidative stress in rat brain. Clin Chim Acta 2004; 340: 229-233
    CrossrefPubMedGoogle Scholar