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Pharm Biol. 2015 May;53(5):739-45. doi: 10.3109/13880209.2014.942787. Epub 2014 Nov 28.

Possible involvement of nitric oxide in antidepressant-like effect of silymarin in male mice.

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Brain and Spinal Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences , Tehran , Iran .



Silymarin (SM) is extracted from milk thistle Silybum marianum L. [Asteraceae (Compositae)] and known for antioxidative and anti-inflammatory effects.


The potential antidepressant-like effect of acute SM and possible involvement of nitric oxide (NO) were determined in male mice.


SM was administered orally (5, 10, 20, 50, 100, and 200 mg/kg; p.o.) 60 min before the tests. After assessment of locomotor activity, the immobility time was measured in forced swimming test (FST) and tail suspension test (TST). To assess the possible involvement of NO, a non-specific NO synthase inhibitor, L-NAME (10 mg/kg, i.p.), and a specific iNOS inhibitor, aminoguanidine (AG) (50 mg/kg, i.p.), were administered separately 30 min before SM (20 and 100 mg/kg).


SM at its effective doses 10, 20, 50, and 100 mg/kg decreased the immobility time in a dose-dependent manner (p < 0.01, p < 0.05, p < 0.05, and p < 0.001, respectively) in FST. SM (10, 20, 50, and 100 mg/kg) also lowered the immobility measure dose dependently in TST (p < 0.01, p < 0.05, p < 0.01, and p < 0.001, respectively). In addition, 50% of maximum response (ED50) of SM was around 10 mg/kg. The dose 100 mg/kg proved the most effective dose in both the tests. Further, this effect was not related to changes in locomotor activity. Moreover, L-NAME reversed the effect of SM (20 and 100 mg/kg) in FST and SM (100 mg/kg) in TST. However, AG did not influence this impact.


The antidepressant-like effect of SM is probably mediated at least in part through NO and SM may increase NO tune.


Depression; forced swimming test; open field test; tail suspension test

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