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 7 h using rodent restraint device preventing them for any physical movement. One hour prior to ARS, silymarinwas administered at doses of 100 mg/kg and 200 mg/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 micewere 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 (100 mg/kg and 200 mg/kg) significantly attenuated immobility time, corticosterone and restored the antioxidant enzymes after ARS. Conclusion: 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.