Antidepressant activity of curcumin: involvement of serotonin and dopamine system

Curcumin is the active molecule in turmeric, a main ingredient in most curries. Curcumin has reported antidepressant properties and this study aimed to better understand the molecular mechanism. The study used an animal model of depression, the forced swim test, and also examined the effects of two doses of curcumin on levels of serotonin and dopamine as well as the effect of adding piperine aka black pepper which increases the absorption of curcumin (a “bioavailability enhancer”). The researchers concluded that the main mechanism of action is the inhibition of monoamine oxidase inhibitor-A, an enzyme that is the target of the MOA-inhibitor class of antidepressant medications, that curcumin can enhance the effect of traditional antidepressant medications like Prozac and Effexor, and that piperine does indeed increase the bioavailability of curcumin.

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.