title: Possible involvement of nitric oxide in antidepressant-like effect of silymarin in male mice.
abstract: BACKGROUND
  Silymarin (SM) is extracted from milk thistle Silybum marianum L. [Asteraceae (Compositae)] and known for antioxidative and anti-inflammatory effects.
  
  
  OBJECTIVE
  The potential antidepressant-like effect of acute SM and possible involvement of nitric oxide (NO) were determined in male mice.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The antidepressant-like effect of SM is probably mediated at least in part through NO and SM may increase NO tune.
authors.affiliation: Brain and Spinal Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Mina
authors.initials: M
authors.lastname: Khoshnoodi
authors.forename: Nahid
authors.initials: N
authors.lastname: Fakhraei
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007103:Immobilization; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012838:Silymarin / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D012838:Silymarin; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester
keywords: Depression; forced swimming test; open field test; tail suspension test