Hydroethanolic extract of Carthamus tinctorius induces antidepressant-like effects: modulation by dopaminergic and serotonergic systems in tail suspension test in mice

Authors

1 Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Urmia Branch, Islamic Azad University, Urmia, Iran

2 Department of Pharmacology & Toxicology, Faculty of Pharmacy, Pharmaceutical Science Branch, Islamic Azad University, Tehran, Iran

Abstract

Objective(s): Studies indicate that major deficiency in the levels of monoaminergic transmitters is a reason for severe depression. On the other hand, it is shown that Carthamus tinctorius L. (CT) may improve neuropsychological injuries by regulation of the monoamine transporter action. Hence, the present study was undertaken to evaluate the involvement of monoaminergic systems in antidepressant-like effect of CT extract in the tail suspension test (TST) in mice.
Materials and Methods: The mice were intraperitoneally (IP) treated with CT extract (100–400 mg/kg) 1hr before the TST. To investigate the involvement of monoaminergic systems in antidepressant-like effect, the mice were treated with receptor antagonists 15 min before CT extract treatment (400 mg/kg, IP) and 1hr before the TST.
Results: Findings showed that CT extract (100–400 mg/kg, IP), dose-dependently induced antidepressant-like effect (P<0.001), but it was not accompanied by alterations in spontaneous locomotor activity in the open-field test. Pretreatment of mice with SCH23390, sulpiride, haloperidol, WAY100135, cyproheptadine, ketanserin and p-chlorophenylalanine (PCPA) inhibited the antidepressant-like effect of CT extract (400 mg/kg, IP), but not with prazosin and yohimbine. Co-administration of CT extract (100 mg/kg, IP) with sub-effective doses of fluoxetine (5 mg/kg, IP) or imipramine (5 mg/kg, IP) increased their antidepressant-like response.
Conclusion: Our findings firstly showed that components (especially N-Hexadecanoic acid) of CT extract induce antidepressant-like effects by interaction with dopaminergic (D1 and D2) and serotonergic (5HT1A, 5-HT2A receptors) systems. These findings validate the folk use of CT extract for the management of depression.

Keywords


1. Nemeroff CB. The burden of severe depression: a review of diagnostic challenges and treatment alternatives. J Psychiatr Res 2007; 41:189-206.

2. Neal MJ. Medical pharmacology at a Glance. 7th ed. John Wiley & Sons; 2012.

3. Howland RD, Mycek MJ, Harvey RA, Champe PC. Lippincott's illustrated reviews: Pharmacology 5th ed. Lippincott Williams & Wilkins; 2006.

4. Meyers S. Monoaminergic supplements as natural antidepressants. Altern Med Rev 2000; 5:64-71.

5. Hasler G. Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatr 2010; 9:155-161.

6. Papakostas GI. Dopaminergic-based pharmacotherapies for depression. Eur Neuropsychopharmacol 2006; 16:391-402.

7. Trevor AJ, Katzung BG, Masters SB, Kruidering-Hall M. Pharmacology Examination & Board Review. 11th ed. McGraw-Hill Medical; 2010.

8. Tamminga CA, Nemeroff CB, Blakely RD, Brady L, Carter CS, Davis KL, et al. Developing novel treatments for mood disorders: accelerating discovery. Biol Psychiatry 2002; 52:589-609.

9. Zhang ZJ. Therapeutic effects of herbal extracts and constituents in animal models of psychiatric disorders. Life Sci 2004; 75:1659-1699.

10. Asgary S, Rahimi P, Mahzouni P, Madani H. Antidiabetic effect of hydroalcoholic extract of Carthamus tinctorius L. in alloxan-induced diabetic rats. J Res Med Sci 2012; 17:386.

11. Zargari A. Medicinal plants. 8th ed.  Tehran University Press; 2014.

12. Abbasi Maleki S. Effect of ethanolic extract of Safflower on naloxone-induced morphine withdrawal signs in mice. Adv Herb Med 2015; 1:9-15.

13. Zhao G, Gai Y, Chu WJ, Qin GW, Guo LH. A novel compound N 1, N 5-(Z)-N 10-(E)-tri-p-coumaroylspermidine isolated from Carthamus tinctorius L. and acting by serotonin transporter inhibition. Eur Neuropsychopharmacol 2009; 19:749-758.

14. Zhao G, Zheng XW, Gai Y, Chu WJ, Qin GW, Guo LH. Safflower extracts functionally regulate monoamine transporters. J Ethnopharmacol 2009; 124:116-124.

15. Al Hashmi LS, Hossain MA, Weli AM, Al-Riyami Q, AlSabahi JN. Gas chromatography–mass spectrometry analysis of different organic crude extracts from the local medicinal plant of Thymus vulgaris L. Asian Pac J Trop Biomed 2013; 3:69-73.

16.  Lorke D. A new approach to practical acute toxicity. Arch Toxicol 1983; 53:275-289.

17. OECD/OCDE 423. OECD web. Consulted 22 May 2009. http://iccvam.niehs.nih.gov/SuppDocs/FedDocs/OECD/OECD GL423.pdf.

18. Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacol 1985; 85:367-370.

19. Jesse CR, Wilhelm EA, Bortolatto CF, Nogueira CW. Evidence for the involvement of the noradrenergic system, dopaminergic and imidazoline receptors in the antidepressant-like effect of tramadol in mice. Pharmacol Biochem Behav 2010; 95:344-350.

20. Voiculescu SE, Rosca AE, Zeca V, Zagrean L, Zagrean AM. Impact of maternal melatonin suppression on forced swim and tail suspension behavioral despair tests in adult offspring. J Med Life 2015; 8:202-206.

21. Piotrowska A, Siwek A, Wolak M, Pochwat B, Szewczyk B, Opoka W, et al. Involvement of the monoaminergic system in the antidepressant-like activity of chromium chloride in the forced swim test. J Physiol Pharmacol 2013; 64:493-498.

22. Przegaliński E, Moryl E, Papp M. The effect of 5-HT 1A receptor ligands in a chronic mild stress model of depression. Neuropharmacol 1995; 34:1305-1310.

23. Tanyeri P, Buyukokuroglu ME, Mutlu O, Ulak G, Akar FY, Celikyurt IK, et al. Involvement of serotonin receptor subtypes in the antidepressant-like effect of  beta receptor agonist Amibegron (SR 58611A): an experimental study. Pharmacol Biochemy Behav 2013; 105:12-16.

24. Gu L, Liu YJ, Wang YB, Yi LT. Role for monoaminergic systems in the antidepressant-like effect of ethanol extracts from Hemerocallis citrina. J Ethnopharmacol  2012; 139:780-787.

25. Binfaré RW, Rosa AO, Lobato KR, Santos AR, Rodrigues AL. Ascorbic acid administration produces an antidepressant-like effect: evidence for the involvement of monoaminergic neurotransmission.  Prog Neuropsychopharmacol Biol Psychiatry  2009 ;30:530-540.

26. Harkin A, Connor T, Walsh M, St John N, Kelly J. Serotonergic mediation of the antidepressant-like effects of nitric oxide synthase inhibitors. Neuropharmacol 2003; 44:616-623.

27. Zheng M, Li Y, Shi D, Liu C, Zhao J. Antidepressant-like effects of flavonoids extracted from Apocynum venetum leaves in mice: the involvement of monoaminergic system in mice. Afr J Pharm Pharmacol 2014; 8:765-774. 

28. Ishola IO, Agbaje EO, Akinleye MO, Ibeh CO, Adeyemi OO. Antidepressant-like effect of the hydroethanolic leaf extract of Alchornea cordifolia (Schumach. & Thonn.) Mull Arg(Euphorbiaceae) in mice: Involvement of monoaminergic system. J Ethnopharmacol  2014; 158:364-372.

29. Brown RE, Corey SC. Moore AK. Differences in Measures of Exploration and Fear in MHC-Congenic C57BL/6J and B6-H-2K Mice. Behav Genet 1999; 29:263.

30. Borsini F, Lecci A, Mancinelli A, D'Aranno V, Meli A. Stimulation of dopamine D-2 but not D-1 receptors reduces immobility time of rats in the forced swimming test: implication for antidepressant activity. Eur J Pharmacol 1988; 148:301-307.

31. Jafarpoor N, Abbasi-Maleki S, Asadi-Samani M, Khayatnouri MH. Evaluation of antidepressant- like effect of hydroalcoholic extract of Passiflora incarnata in animal models of depression in male mice. J Herb Med Pharmacol 2014 ; 3:41- 45.

32. Moallem SA, Hosseinzadeh H, Ghoncheh F. Evaluation of antidepressant  effects of aerial parts  of  echium vulgare on mice . Iran J Basic Med Sci 2007; 10:189-196.

33. Shahamat Z, Abbasi-Maleki S, Mohammadi Motamed S. Evaluation of antidepressant-like effects of aqueous and ethanolic extracts of Pimpinella anisum fruit in mice. Avicenna J Phytomed 2016; 6:322-328.

34. Jia LH, Liu Y, Li YZ. Rapid determination of volatile constituents in safflower from Xinjiang and Henan by ultrasonic-assisted solvent extraction and GC–MS. J Pharm Anal 2011; 1: 213–218.

35. Bazinet RP, Laye S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci 2014; 15:771–785.

36. Henry GE, Momin RA, Nair MG, Dewitt DL. Antioxidant and cyclooxygenase activities of fatty acids found in food. J Agric Food Chem 2002; 50:2231-2234.

37. Elagbar ZA, Naik RR, Shakya AK, Bardaweel SK. Fatty ascids analysis, antioxidant and biological activity of fixed oil of annona muricata L. Seeds. J Chem 2016;2016: 1-6.

38. Yoshida Y, Niki E. Antioxidant effects of phytosterol and its components. J Nutr Sci Vitaminol (Tokyo) 2003; 49:277-280.

39. Scapagnini G, Davinelli S, Drago F, De Lorenzo A, Oriani G. Antioxidants as antidepressants: fact or fiction?. CNS Drugs 2012; 26:477-490.

40. Slamon ND, Pentreath VW. Antioxidant defense against antidepressants in C6 and 1321N1 cells.Chem Biol Interact 2000; 127:181-199.

41. Kolla N, Wei Z, Richardson JS, Li XM. Amitriptyline and fluoxetine protect PC12 cells from cell death induced by hydrogen peroxide. J Psychiatry Neurosci 2005; 30:196–201.

42. Elhwuegi AS. Central monoamines and their role in major depression. Prog Neuro-Psychopharmacol Biol Psychiatr 2004; 28:435-451.

43. Risch SC, Nemeroff CB. Neurochemical alterations of serotonergic neuronal systems in depression. J Clin Psychiatry. J Clin Psychiatry 1992; 53:3-7.

44. Willner P, Hale AS, Argyropoulos S. Dopaminergic mechanism of antidepressant action in depressed patients. J Affect Disord  2005; 86:37-45.

45. Hirano S, Miyata S, Onodera K, Kamei J. Involvement of dopamine D 1 receptors and α 1-adrenoceptors in the antidepressant-like effect of chlorpheniramine in the mouse tail suspension test. Eur J Pharmacol 2007; 562:72-76.

46. Machado DG, Kaster MP, Binfaré RW, Dias M, Santos AR, Pizzolatti MG, et al. Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system. Prog Neuro-Psychopharmacol Biol Psychiatr 2007; 31:421-428.

47. Wæhrens J, Gerlach J. Bromocriptine and imipramine in endogenous depression: a double-blind controlled trial in out-patients. J Affect Disord 1981; 3:193-202.

48. Marien MR, Colpaert FC, Rosenquist AC. Noradrenergic mechanisms in neurodegenerative diseases: a theory. Brain Res Rev 2004; 45:38-78.

49. Haider S, Khaliq S, Haleem DJ. Enhanced serotonergic neurotransmission in the hippocampus following tryptophan administration improves learning acquisition and memory consolidation in rats. Pharmacol Rep 2007; 59:53.

50. Celada P, Puig MV, Amargós-Bosch M, Adell A, Artigas F. The therapeutic role of 5-HT 1A and 5-HT 2A receptors in depression. Psychiatry Neurosci 2004; 29:252.

51. Shrestha S, Hirvonen J, Hines CS, Henter ID, Svenningsson P, Pike VW, et al. Serotonin-1A receptors in major depression quantified using PET: controversies, confounds, and recommendations. Neuroimage 2012; 59:3243-3251.

52. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002; 34:13-25.

53. Machado DG, Bettio LE, Cunha MP, Capra JC, Dalmarco JB, Pizzolatti MG, et al. Antidepressant-like effect of the extract of Rosmarinus officinalis in mice: involvement of the monoaminergic system. Prog Neuro-Psychopharmacol Biol Psychiatr 2009; 33:642-650.

54. Kuehnl S, Schroecksnadel S, Temml V, Gostner JM, Schennach H, Schuster D, et al. Lignans from Carthamus tinctorius suppress tryptophan breakdown via indoleamine 2, 3-dioxygenase. Phytomed 2013; 20:1190-1195.

55. Frazer A. Norepinephrine involvement in antidepressant action. J Clin Psychiatry 2000; 61:25-30.

56. Nutt DJ, Baldwin DS, Clayton AH. The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 2006; 67:3-8.

57. Sarris J, Kavanagh DJ, Byrne G. Adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines. J Psychiatr Res 2010; 44:32-41.

58. Lam RW, Wan DD, Cohen NL, Kennedy SH. Combining antidepressants for treatment resistant depression: a review. J Clin Psychiatry 2002; 63:685-693.