• Harshita Jain Department of Pharmacology, School of Pharmacy, Chouksey Engineering College, Bilaspur - 495 004, Chhattisgarh, India
  • Prateek Jain Department of Chemistry, ADINA Institute of Pharmaceutical Sciences, Sagar, Madhya Pradesh - 470 002, India.
  • Bharti Ahirwar Department of Pharmacy, Guru Ghasidas Central University, Bilaspur - 495 009, Chhattisgarh, India.
  • Dheeraj Ahirwar Department of Pharmacology, School of Pharmacy, Chouksey Engineering College, Bilaspur - 495 004, Chhattisgarh, India



 Objective: Present study aimed to evaluate the antidepressant-like activity of thymoquinone (TQ) in unstressed and stressed condition and to explore the possible underlying mechanism for this activity.

Methods: TQ (5, 10, and 20 mg/kg) and fluoxetine per se were administered to the unstressed and stressed mice; immobility periods were observed using forced swim test (FST) and tail suspension test (TST). Effect of corticotropin-releasing factor (CRF)-1 antagonist on antidepressant-like activity was also evaluated. The mechanism of action was also explored by measuring plasma corticosterone levels.

Results: TQ (20 mg/kg) and fluoxetine per se significantly decreased immobility periods in stressed mice indicating significant antidepressant-like activity under stress. There was no significant effect on locomotor activity of the mice on treatment with TQ and fluoxetine per se. It significantly decreased plasma corticosterone level. Antalarmin (a CRF-1 receptor antagonist) significantly attenuated TQ induced the antidepressant-like effect in both FST and TST.

Conclusion: TQ significantly produced antidepressant-like activity in mice possi‑bly through inhibiting CRF activity and decreasing plasma corticosterone levels.


Keywords: Immobilization, Thymoquinone, Corticotrophin-releasing factor.


1. Liotti M, Mayberg HS. The role of functional neuroimaging in the neuropsychology of depression. J Clin Exp Neuropsychol 2001;23(1):121-36.
2. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002;34(1):13-25.
3. Bale TL, Vale WW. Increased depression-like behaviors in corticotrophin releasing factor receptor-2-deficient mice: Sexually dichotomous responses. J Neurosci 2003;23(12):5295-301.
4. Vale W, Spiess J, Rivier C, Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotrophin and beta-endorphin. Science 1981;213(4514):1394-7.
5. Nemeroff CB. The role of corticotropin-releasing factor in the pathogenesis of major depression. Pharmacopsychiatry 1988;21(2):76-82.
6. Nemeroff CB. New vistas in neuropeptide research in neuropsychiatry: Focus on corticotropin-releasing factor. Neuropsychopharmacology 1992;6(2):69-75.
7. Holsboer F. The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. J Psychiatr Res 1999;33(3):181-214.
8. Reul JM, Holsboer F. Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression. Curr Opin Pharmacol 2002;2(1):23-33.
9. Arborelius L, Owens MJ, Plotsky PM, Nemeroff CB. The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol 1999;160(1):1-12.
10. Carrasco GA, Van de Kar LD. Neuroendocrine pharmacology of stress. Eur J Pharmacol 2003;463(1-3):235-72.
11. Bale TL, Vale WW. CRF and CRF receptors: Role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol 2004;44:525-57.
12. Owens MJ, Nemeroff CB. Physiology and pharmacology of corticotropin-releasing factor. Pharmacol Rev 1991;43(4):425-73.
13. Lavicky J, Dunn AJ. Corticotropin-releasing factor stimulates catecholamine release in hypothalamus and prefrontal cortex in freely moving rats as assessed by microdialysis. J Neurochem 1993;60(2):602-12.
14. Price ML, Lucki I. Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor. J Neurosci 2001;21(8):2833-41.
15. Valentino RJ, Commons KG. Peptides that fine-tune the serotonin system. Neuropeptides 2005;39(1):1-8.
16. Charney DS. Psychobiological mechanisms of resilience and vulnerability: Implications for successful adaptation to extreme stress. Am J Psychiatry 2004;161(2):195-216.
17. Borah A, Singha B, Phukan S. Anti-depressant effect of ceftriaxone in forced swimming test and in tail suspension test in mice. Int J Pharm Pharm Sci 2016;8(11):191-4.
18. Abdel-Fattah AM, Matsumoto K, Watanabe H. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol 2000;400(1):89-97.
19. Hassan M, El-Dakhakhny AM. Effect of some Nigela sativa constituents on chemical carcinogenesis in hamster cheek pouch. J Egypt Soc Pharmacol Exp Ther 1992;11:675-7.
20. Houghton PJ, Zarka R, de las Heras B, Hoult JR. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med 1995;61(1):33-6.
21. Al-Majed AA, Al-Omar FA, Nagi MN. Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus. Eur J Pharmacol 2006;543(1-3):40-7.
22. Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri MT. Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. Med Sci Monit 2005;11(4):BR106-10.
23. Hamdy NM, Taha RA. Effects of Nigella sativa oil and thymoquinone on oxidative stress and neuropathy in streptozotocin-induced diabetic rats. Pharmacology 2009;84(3):127-34.
24. El-Mahmoudy A, Matsuyama H, Borgan MA, Shimizu Y, El-Sayed MG, Minamoto N, et al. Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages. Int Immunopharmacol 2002;2(11):1603-11.
25. Mohamed A, Afridi DM, Garani O, Tucci M. Thymoquinone inhibits the activation of NF-kappaB in the brain and spinal cord of experimental autoimmune encephalomyelitis. Biomed Sci Instrum 2005;41:388-93.
26. Sethi G, Ahn KS, Aggarwal BB. Targeting nuclear factor-kappa B activation pathway by thymoquinone: Role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Res 2008;6(6):1059-70.
27. El-Mahmoudy A, Shimizu Y, Shiina T, Matsuyama H, Nikami H, Takewaki T. Macrophage-derived cytokine and nitric oxide profiles in Type I and Type II diabetes mellitus: Effect of thymoquinone. Acta Diabetol 2005;42(1):23-30.
28. Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine 2004;11(1):56-64.
29. Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology (Berl) 1985;85(3):367-70.
30. Dhingra D, Kumar V. Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice. Indian J Pharmacol 2008;40(4):175-9.
31. Dattatray BP, Padmaja AM, Nirmala NR. Antidepressant activity of aqueous extracts of fruits of terminalia chebula and phyllanthus emblica in behavioral models of depression: Involvement of monoaminergic system. Int J Pharm Pharm Sci 2014;6(8):615-20.
32. Gilhotra N, Dhingra D. Involvement of NO-cGMP pathway in anti-anxiety effect of aminoguanidine in stressed mice. Prog Neuropsychopharmacol Biol Psychiatry 2009;33(8):1502-7.
33. Nakane T, Audhya T, Hollander CS, Schlesinger DH, Kardos P, Brown C, et al. Corticotrophin-releasing factor in extra-hypothalamic brain of the mouse: Demonstration by immunoassay and immunoneutralization of bioassayable activity. J Endocrinol 1986;111(1):143-9.
34. Delawary M, Tezuka T, Kiyama Y, Yokoyama K, Inoue T, Hattori S, et al. NMDAR2B tyrosine phosphorylation regulates anxiety-like behavior and CRF expression in the amygdala. Mol Brain 2010;3:37.
35. Bartos J, Pesez M. Colorimetric and fluorimetric determination of steroids. Pure Appl Chem 1979;51(10):2157-9.
36. Dunn AJ, Swiergiel AH. Effects of interleukin-1 and endotoxin in the forced swim and tail suspension tests in mice. Pharmacol Biochem Behav 2005;81(3):688-93.
37. Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: A primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977;229(2):327-36.
38. Thierry B, Stéru L, Simon P, Porsolt RD. The tail suspension test: Ethical considerations. Psychopharmacology (Berl) 1986;90(2):284-5.
39. Willner P. The validity of animal models of depression. Psychopharmacology (Berl) 1984;83(1):1-16.
40. Barden N. Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression. J Psychiatry Neurosci 2004;29:185-93.
41. Johnson SA, Fournier NM, Kalynchuk LE. Effect of different doses of corticosterone on depression-like behavior and HPA axis responses to a novel stressor. Behav Brain Res 2006;168(2):280-8.
42. Li S, Wang C, Wang M, Li W, Matsumoto K, Tang Y. Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. Life Sci 2007;80(15):1373-81.
43. Murray F, Smith DW, Hutson PH. Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur J Pharmacol 2008;583(1):115-27.
212 Views | 473 Downloads
How to Cite
Jain, H., P. Jain, B. Ahirwar, and D. Ahirwar. “ANTIDEPRESSANT ACTIVITY OF THYMOQUINONE POSSIBLY THROUGH INVOLVEMENT OF CORTICOTROPIN RELEASING FACTOR”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 11, Nov. 2017, pp. 392-6, doi:10.22159/ajpcr.2017.v10i11.21773.
Original Article(s)