title: Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: Modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus.
abstract: BACKGROUND
  Silymarin is a polyphenolic flavanoid of Silybum marianum, elicited neuroprotection and antidepressant like activity in stressed model. It was found to increase 5-hydroxytryptamine (5-HT) levels in the cortex and dopamine (DA) and norepinephrine (NE) in the cerebellum in normal mice. The aim of the present study was to investigate the potential antidepressant-like activity of silymarin in the acute restraint stress (ARS) in mice.
  
  
  METHODS
  The ARS was induced by immobilizing the mice for a period of 7h using rodent restraint device preventing them for any physical movement. One hour prior to ARS, silymarin was administered at doses of 100mg/kg and 200mg/kg per oral to non stressed and ARS mice. Various behavioral parameters like immobility time in force swim test, locomotor activity in open field test, and biochemical alterations, serum corticosterone, 5-HT, DA, NE level, malondialdehyde (MDA), and antioxidant enzymes (GSH, CAT and SOD) in hippocampus and cerebral cortex in non stressed and ARS subjected mice were investigated.
  
  
  RESULTS
  Experimental findings reveals mice subjected to ARS exhibited significant increase immobility time, serum corticosterone, MDA formation and impaired SOD and CAT activities in hippocampus and cerebral cortex as compared to non stressed mice. Silymarin treatment (100mg/kg and 200mg/kg) significantly attenuated immobility time, corticosterone and restored the antioxidant enzymes after ARS.
  
  
  CONCLUSIONS
  The present experimental findings indicate that silymarin exhibits antidepressant like activity probably either through alleviating oxidative stress by modulation of corticosterone response, and antioxidant defense system in hippocampus and cerebral cortex in ARS mice.
authors.affiliation: Department of Pharmacology, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, 410401, Pune, Maharashtra, India; Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382 481, Gujarat, India.
authors.forename: Vishnu N
authors.initials: VN
authors.lastname: Thakare
authors.affiliation: Research and Development, Astec Life Sciences, Mumbai, Maharashtra, India.
authors.forename: Valmik D
authors.initials: VD
authors.lastname: Dhakane
authors.affiliation: Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382 481, Gujarat, India. Electronic address: drbhoomikampatel@gmail.com.
authors.forename: Bhoomika M
authors.initials: BM
authors.lastname: Patel
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D012149:Restraint, Physical / Q000523:psychology; D012701:Serotonin / Q000378:metabolism; D012838:Silymarin / Q000494:pharmacology*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D000975:Antioxidants; D012838:Silymarin; D012701:Serotonin; D003345:Corticosterone
keywords: Acute restraint stress; Hippocampus; Oxidative stress; Serum corticosterone; Silymarin