Psychopharmacology

, 201:435 | Cite as

Antidepressant activity of curcumin: involvement of serotonin and dopamine system

  • Shrinivas K. Kulkarni
  • Mohit Kumar Bhutani
  • Mahendra Bishnoi
Original Investigation

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.

Keywords

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

References

  1. Ammon HP, Wahl MA (1991) Pharmacology of Curcuma longa. Planta Med 57:1–7PubMedCrossRefGoogle 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):41–52PubMedCrossRefGoogle 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):13–21PubMedGoogle 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):297–304PubMedCrossRefGoogle Scholar
  5. Blier P, De Montigny C (1994) Current advances and trends in the treatment of depression. Trends Pharmacol Sci 15:220–226PubMedCrossRefGoogle 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 206:533–540PubMedCrossRefGoogle Scholar
  7. Dar A, Khatoon S (2000) Behavioral and biochemical studies of dichloromethane fraction from the Areca catechu nut. Pharmacol Biochem Behav 65:1–6PubMedCrossRefGoogle Scholar
  8. Deodhar SD, Sethi R, Srimal RC (1980) Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res 71:632–34PubMedGoogle 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):177–185Google 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):329–335PubMedCrossRefGoogle 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 101:31–35PubMedGoogle Scholar
  12. Elhwuegi AS (2004) Central monoamines and their role in major depression. Prog Neuropsychopharmacol 28:435–51CrossRefGoogle Scholar
  13. Kiso Y, Suzuki Y, Watanabe N, Oshima Y, Hikino H (1983) Antihepatotoxic principles of Curcuma longa rhizomes. Planta Med 49(3):185–87CrossRefGoogle Scholar
  14. Kulkarni SK, Mehta AK (1985) Purine nucleoside-mediated immobility in mice: reversal by antidepressants. Psychopharmacology (Berl) 85(4):460–463CrossRefGoogle 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 6:10PubMedCrossRefGoogle 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):197–203PubMedCrossRefGoogle Scholar
  17. Mazzio EA, Harris N, Soliman KF (1998) Food constituents attenuate oxidase activity and peroxide levels in C6 cells. Planta Med 64:603–607PubMedCrossRefGoogle Scholar
  18. Naughton M, Mulrooney JB, Leonard BE (2000) A review of the role of serotonin receptors in psychiatric disorders. Hum Psychopharmacol Clin Exp 15:397–415CrossRefGoogle 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 51:291–294PubMedCrossRefGoogle 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 55:259–266PubMedGoogle Scholar
  21. Schloss P, Henm FA (2004) New insights into the mechanisms of antidepressant therapy. Pharmacol Ther 102:47–60PubMedCrossRefGoogle Scholar
  22. Schurr A, Livne A (1975) Differential inhibition of mitochondrial monoamine oxidase from brain by hashish components. Biochem Pharm 25:1201–1203Google 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 25:415–423PubMedCrossRefGoogle 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):353–356PubMedCrossRefGoogle Scholar
  25. Sreejayan R, Rao MN (1994) Curcuminoids as potent inhibitors of lipid peroxidation. J Pharm Pharmacol 46:1013–1016PubMedGoogle Scholar
  26. Srinivasan M (1972) Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci 26(4):269–270PubMedGoogle Scholar
  27. Srivastava R, Dikshit M, Srimal RC, Dhawan BN (1985) Antithrombotic effect of curcumin. Thromb Res 40(3):413–417PubMedCrossRefGoogle 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):43–50PubMedCrossRefGoogle 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 518:40–46PubMedCrossRefGoogle 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 82:200–206PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Shrinivas K. Kulkarni
    • 1
    • 2
  • Mohit Kumar Bhutani
    • 1
  • Mahendra Bishnoi
    • 2
  1. 1.Pharmacology Division, University Institute of Pharmaceutical SciencesPanjab UniversityChandigarhIndia
  2. 2.Centre with Potential for Excellence in Biomedical Sciences (CPEBS)Panjab UniversityChandigarhIndia

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