Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment

Santoshkumar Tota, Pradeep Kumar Kamat, Rakesh Shukla, Chandishwar Nath

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Recently, silibinin, a clinically used hepatoprotectant, has been reported to prevent amyloid beta induced memory impairment by reducing oxidative stress and inflammation in mice brain. However, the exact mechanism of neuroprotective effect of silibinin has not been properly studied especially in context of brain energy metabolism and cholinergic functions, the essential factors that undergo impairment in Alzheimer's disease. Therefore, the present study investigated the effect of silibinin on impairment in memory, brain energy metabolism and cholinergic function following intracerebral (IC) streptozotocin (STZ) administration in mice. STZ (0.5. mg/kg), administered twice at an interval of 48. h, caused significant memory impairment tested by Morris water maze. Further, STZ significantly decreased ATP and increased synaptosomal calcium level in mice brain. Increased oxidative and nitrosative stress was also observed in IC STZ injected mice brain. STZ IC induced memory impairment is associated with increased activity and mRNA expression of acetylcholinesterase (AChE) and decreased α-7 nicotinic acetylcholine receptor (α-7-nAChR) mRNA expression in mice brain. Pretreatment with silibinin (100 and 200. mg/kg, po) attenuated STZ induced memory impairment by reducing oxidative and nitrosative stress and synaptosomal calcium ion level. Further, silibinin dose dependently restored ATP level indicating improvement in brain energy metabolism. The activity and mRNA expression of AChE was restored by silibinin. Moreover, α-7-nAChR mRNA expression was significantly increased by silibinin in STZ treated mice brain. The present study clearly demonstrates that beneficial effects of silibinin in STZ induced memory impairment in mice is due to improvement in brain energy metabolism and cholinergic function.

Original languageEnglish (US)
Pages (from-to)207-215
Number of pages9
JournalBehavioural Brain Research
Volume221
Issue number1
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Keywords

  • Acetylcholinesterase expression
  • Brain energy metabolism
  • Memory impairment
  • Oxidative stress
  • Silibinin
  • Streptozotocin

ASJC Scopus subject areas

  • Behavioral Neuroscience

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