Antidepressant activity of curcumin: involvement of serotonin and dopamine system

Abstract

Rationale

Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions.

Objective

The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin.

Methods and observations

Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10–80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities.

Conclusion

The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Ammon HP, Wahl MA (1991) Pharmacology of Curcuma longa. Planta Med 57:1–7

    PubMed  Article  CAS  Google Scholar 

  2. Arun N, Nalini N (2002) Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats. Plant Foods Hum Nutr 57(1):41–52

    PubMed  Article  CAS  Google Scholar 

  3. Babu PS, Srinivasan K (1995) Influence of dietary curcumin and cholesterol on the progression of experimentally induced diabetes in albino rat. Mol Cell Biochem 152(1):13–21

    PubMed  CAS  Google Scholar 

  4. Beyer CE, Boikess S, Luo B, Dawson LA (2002) Comparison of the effects of antidepressants on norepinephrine and serotonin concentrations in the rat frontal cortex: an in-vivo microdialysis study. J Psychopharmacol 16(4):297–304

    PubMed  CAS  Article  Google Scholar 

  5. Blier P, De Montigny C (1994) Current advances and trends in the treatment of depression. Trends Pharmacol Sci 15:220–226

    PubMed  Article  CAS  Google Scholar 

  6. Brouet I, Ohshima H (1995) Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun 206:533–540

    PubMed  Article  CAS  Google Scholar 

  7. Dar A, Khatoon S (2000) Behavioral and biochemical studies of dichloromethane fraction from the Areca catechu nut. Pharmacol Biochem Behav 65:1–6

    PubMed  Article  CAS  Google Scholar 

  8. Deodhar SD, Sethi R, Srimal RC (1980) Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res 71:632–34

    PubMed  CAS  Google Scholar 

  9. Dhir A, Kulkarni SK (2007) Involvement of nitric oxide (NO) signaling pathway in the antidepressant action of bupropion, a dopamine reuptake inhibitor. Eur J Pharmacol 568(1–3):177–185

    Google Scholar 

  10. Dhir A, Naidu PS, Kulkarni SK (2005) Protective effect of cyclooxygenase-2 (COX-2) inhibitors but not non-selective cyclooxygenase (COX)-inhibitors on ethanol withdrawal-induced behavioural changes. Addict Biol 10(4):329–335

    PubMed  Article  CAS  Google Scholar 

  11. Dikshit M, Rastogi L, Shukla R, Srimal RC (1995) Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart. Indian J Med Res 101:31–35

    PubMed  CAS  Google Scholar 

  12. Elhwuegi AS (2004) Central monoamines and their role in major depression. Prog Neuropsychopharmacol 28:435–51

    Article  CAS  Google Scholar 

  13. Kiso Y, Suzuki Y, Watanabe N, Oshima Y, Hikino H (1983) Antihepatotoxic principles of Curcuma longa rhizomes. Planta Med 49(3):185–87

    Article  CAS  Google Scholar 

  14. Kulkarni SK, Mehta AK (1985) Purine nucleoside-mediated immobility in mice: reversal by antidepressants. Psychopharmacology (Berl) 85(4):460–463

    Article  Google Scholar 

  15. Lao CD, Ruffin MT 4th, Normolle D, Heath DD, Murray SI, Bailey JM, Boggs ME, Crowell J, Rock CL, Brenner DE (2006) Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 6:10

    PubMed  Article  CAS  Google Scholar 

  16. Limtrakul P, Lipigorngoson S, Namwong O, Apisariyakul A, Dunn FW (1997) Inhibitory effect of dietary curcumin on skin carcinogenesis in mice. Cancer Lett 116(2):197–203

    PubMed  Article  CAS  Google Scholar 

  17. Mazzio EA, Harris N, Soliman KF (1998) Food constituents attenuate oxidase activity and peroxide levels in C6 cells. Planta Med 64:603–607

    PubMed  Article  CAS  Google Scholar 

  18. Naughton M, Mulrooney JB, Leonard BE (2000) A review of the role of serotonin receptors in psychiatric disorders. Hum Psychopharmacol Clin Exp 15:397–415

    Article  CAS  Google Scholar 

  19. Porsolt RD, Bertin A, Jalfre M (1978) Behavioural despair in rats and mice: strain differences and the effects of imipramine. Eur J Pharmacol 51:291–294

    PubMed  Article  CAS  Google Scholar 

  20. Rao CV, Rivenson A, Simi B et al (1995) Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res 55:259–266

    PubMed  CAS  Google Scholar 

  21. Schloss P, Henm FA (2004) New insights into the mechanisms of antidepressant therapy. Pharmacol Ther 102:47–60

    PubMed  Article  CAS  Google Scholar 

  22. Schurr A, Livne A (1975) Differential inhibition of mitochondrial monoamine oxidase from brain by hashish components. Biochem Pharm 25:1201–1203

    Google Scholar 

  23. Serra G, Agriolas A, Klimek V, Fadda F, Gessa GL (1979) Chronic treatment with antidepressants prevents the inhibitory effect of small doses of apomorphine on dopamine synthesis and motor activity. Life Sci 25:415–423

    PubMed  Article  CAS  Google Scholar 

  24. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 64(4):353–356

    PubMed  Article  CAS  Google Scholar 

  25. Sreejayan R, Rao MN (1994) Curcuminoids as potent inhibitors of lipid peroxidation. J Pharm Pharmacol 46:1013–1016

    PubMed  CAS  Google Scholar 

  26. Srinivasan M (1972) Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci 26(4):269–270

    PubMed  CAS  Google Scholar 

  27. Srivastava R, Dikshit M, Srimal RC, Dhawan BN (1985) Antithrombotic effect of curcumin. Thromb Res 40(3):413–417

    PubMed  Article  CAS  Google Scholar 

  28. Wang R, Xu Y, Wu HL, Li YB, Li YH, Guo JB, Li XJ (2008) The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors. Eur J Pharmacol 578(1):43–50

    PubMed  Article  CAS  Google Scholar 

  29. Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ (2005a) The effects of curcumin on depressive-like behaviors in mice. Eur J Pharmacol 518:40–46

    PubMed  Article  CAS  Google Scholar 

  30. Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ (2005b) Antidepressant effects of curcumin in the forced swimming test and olfactory bulbactomy models of depression in rats. Pharmacol Biochem Behav 82:200–206

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgement

This study was carried out in Centre with Potential of Excellence in Biomedical Sciences (CPEBS), Panjab University, Chandigarh. The technical assistance of Ms. Manninder Kaur, J. Gr II, is very much appreciated.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Shrinivas K. Kulkarni.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kulkarni, S.K., Bhutani, M.K. & Bishnoi, M. Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology 201, 435 (2008). https://doi.org/10.1007/s00213-008-1300-y

Download citation

Keywords

  • Curcumin
  • Forced swim test (FST)
  • Serotonin
  • Monoamine oxidase (MAO)
  • Piperine