الفهرس 
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Abstract
Depression is a widespread, debilitating psychiatric illness with significant economic and social consequences. In clinical practice there are three main kinds of antidepressants including TCAs, MAOIs and SSRIs. Most of these drugs present many problems such as undesirable side-effects, relapse, refractory patients, and delayed onset of action. Therefore, there is pressing need for new antidepressant drugs. Thus, developing safe and effective agents from traditional herbs may provide us a good way to lessen the side effects as well as improve the efficacy.
The present study aimed to investigate the antidepressant effect of curcumin and cocoa powder on experimentally induced animal model of depression (depression was induced by injection of reserpine) with comparison with well-established antidepressant drugs; fluoxetine and tryptophan. The safety effect of curcumin and cocoa powder on liver and kidney functions was evaluated.
The analytical measurements were done on 200 male albino rats, divided equally into two main groups:
Group I (GI): control group: included 100 rats and were subdivided equally into 5 subgroups: normal control, tryptophan, fluoxetine, curcumin and cocoa powder subgroups.
Group II (GII): depressed group: included 100 rats and were i.p. injected with reserpine for 14 days to establish the animal model of depression. Starting from the 15th day of daily reserpine injection, animals were divided equally into the following 5 subgroups: reserpinized animals (without treatment), tryptophan treated, fluoxetine treated, curcumin treated and cocoa powder treated subgroups. After 14 and 30 days of daily treatment with the previous treatments, the following studies were made:
I. Behavioral studies: immobility time was measured to evaluate the antidepressant effect of different treatments.
II. Biochemical studies: sera were collected and the following parameters were measured:
A) Liver function tests: serum alanine transaminase and aspartate transaminase activities were measured to evaluate the safety of different treatments on liver.
B) Kidney function tests: serum urea and creatinine levels were measured to evaluate the safety of different treatments on kidney.
III. Neurochemical studies: 5-HT, NE and DA neurotransmitters were measured in cerebral cortex and hippocampus brain areas.
Results of the study indicated:
I. Behavioral studies:
1- Chronic reserpine administration to adult male albino rats for 28 and 44 days induced a significant increase in immobility time in the forced swim test.
2- The daily treatment of reserpinized rats with tryptophan for 14 and 30 days restored the significant increase in immobility period induced by reserpine to non-significant change.
3- The significant increase in the duration of immobility time induced by reserpine in the reserpinized rats did not changed after 14 days of daily fluoxetine treatment. However, after 30 days of daily fluoxetine treatment, the increase in immobility time returned to control like value.
4- The daily treatment of reserpinized rats with curcumin for 14 and 30 days reduced the significant increase in immobility time to normal control level.
5- The daily treatment of reserpinized rats with cocoa powder for 14 and 30 days restored the significant increase in immobility time to normal control like value.
II. Biochemical studies:
a) Liver functions:
1- Non-significant changes in serum ALT and AST activities were observed after 28 and 44 days of daily reserpine injection.
2- The daily treatment of normal control and reserpinized rats with tryptophan for 14 and 30 days induced non-significant changes in serum ALT and AST activities.
3- The daily treatment of normal control and reserpinized rats with fluoxetine for 14 days induced non-significant changes in serum ALT and AST activities. However, 30 days of daily fluoxetine treatment to control and reserpinized rats induced non-significant change in serum ALT activity and significant decrease in AST activity as compared with normal control group.
4- Non-significant changes in serum ALT and AST were observed after daily treatment of normal and reserpinized rats with curcumin for 14 and 30 days.
5- The daily oral administration of cocoa powder to normal and reserpinized rats for 14 and 30 days induced non-significant changes in serum ALT and AST activities.
B) Kidney functions:
1- The daily reserpine injection to adult male albino rats for 28 and 44 days resulted in a significant increase in serum urea levels above normal control values. However, creatinine levels showed non-significant change after 28 days and a significant increase after 44 days of reserpine injection.
2- The daily administration of tryptophan to control rats induced a significant increase in serum urea level after 14 days which turned to non-significant change after 30 days of tryptophan treatment as compared to normal control values. Non-significant change in serum creatinine levels was observed after 14 and 30 days of tryptophan treatment to control rats. The treatment of reserpinized rats with tryptophan for 14 and 30 days failed to change the significant increase in serum urea levels induced by reserpine. Non-significant change in serum creatinine levels of reserpinized rats treated daily with tryptophan for 14 days was recorded. The treatment of reserpinized rats with tryptophan for 30 days did not change the significant increase in serum creatinine level induced by reserpine injection.
3- Non-significant changes in serum urea levels were recorded in control and reserpinized rats treated with fluoxetine for 14 days. However, daily treatment with fluoxetine for 30 days induced significant increase in serum urea levels of control and reserpinized rats. Non-significant changes in serum creatinine levels were observed in control rats treated daily with fluoxetine for 14 and 30 days. However, fluoxetine treatment to reserpinized rats had no effect on significant increase in serum creatinine levels induced by reserpine injection.
4- The daily administration of curcumin for 14 and 30 days to control rats induced non-significant changes in serum urea and creatinine levels. The significant increase in serum urea and creatinine levels induced by reserpine injection was returned to control-like values by curcumin treatment for 14 and 30 days to reserpinized rats.
5- A significant increase in serum urea level was resulted by daily cocoa powder treatment for 14 days to control rats. However, after 30 days of daily cocoa powder treatment to control rats, non-significant change in serum urea level was recorded. The daily treatment of reserpinized rats with cocoa powder for 14 and 30 days returned the significant increase in serum urea and creatinine levels induced by reserpine injection to control-like values.
III. Neurochemical studies:
1- Administration of reserpine for 28 and 44 days depleted the cortical and hippocampal monoamines.
2- Administration of tryptophan for 14 and 30 days to reserpinized rats returned the significant decrease in cortical 5-HT and DA to normal control levels. However, treatment with tryptophan for 14 and 30 days failed to return the significant decrease in cortical NE to normal control levels. In the hippocampus, treatment of reserpinized rats with tryptophan either for 14 or 30 days did not change the significant decrease induced by reserpine in cortical and hippocampal monoamines.
3- Treatment of reserpinized rats with fluoxetine for 14 days did not affect the significant decrease induced by reserpine injection in cortical and hippocampal monoamines. After 30 days of daily fluoxetine treatment, the significant decrease in cortical 5-HT and DA changed to non-significant changes without affecting the significant decrease in cortical NE induced by reserpine. In hippocampus of reserpinized rats treated with fluoxetine for 30 days, the 5-HT level showed a control like value while the significant decrease in NE and DA levels induced by reserpine was still the same with no change.
4- The daily treatment of reserpinized rats for 14 and 30 days with curcumin returned the significant decrease in cortical monoamines to normal control-like values. In hippocampus of reserpinized rats, daily treatment with curcumin for 14 and 30 days restored the significant decrease induced by reserpine in NE and DA to non-significant decrease. However, hippocampal 5-HT showed a significant decrease after 14 days and non-significant decrease after 30 days of daily curcumin treatment.
5- The daily treatment of reserpinized rats for 14 and 30 days with cocoa powder restored the significant decrease induced by reserpine in cortical monoamines to normal control levels. In hippocampus of reserpinized rats, the daily treatment with cocoa powder for 14 days restore the significant decrease in hippocampal NE and DA levels induced by reserpine to normal control values, but failed to affect the significant decrease induced by reserpine in 5-HT level. However, the daily treatment of reserpinized rats with cocoa powder for 30 days returned the significant decrease in hippocampal monoamines to normal control levels.
It could be concluded that curcumin and cocoa powder succeeded to restore the depletion in the cortical and hippocampal monoamines induced by reserpine to the control like-values, which may explain their efficacy to be used as antidepressants.