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Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment.
Behav Brain Res. 2011 Aug 01; 221(1):207-15.BB

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 (0.5mg/kg), administered twice at an interval of 48h, 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 200mg/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.

Authors+Show Affiliations

Division of Pharmacology, Central Drug Research Institute, CSIR, Lucknow, UP, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21382422

Citation

Tota, Santoshkumar, et al. "Improvement of Brain Energy Metabolism and Cholinergic Functions Contributes to the Beneficial Effects of Silibinin Against Streptozotocin Induced Memory Impairment." Behavioural Brain Research, vol. 221, no. 1, 2011, pp. 207-15.
Tota S, Kamat PK, Shukla R, et al. Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment. Behav Brain Res. 2011;221(1):207-15.
Tota, S., Kamat, P. K., Shukla, R., & Nath, C. (2011). Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment. Behavioural Brain Research, 221(1), 207-15. https://doi.org/10.1016/j.bbr.2011.02.041
Tota S, et al. Improvement of Brain Energy Metabolism and Cholinergic Functions Contributes to the Beneficial Effects of Silibinin Against Streptozotocin Induced Memory Impairment. Behav Brain Res. 2011 Aug 1;221(1):207-15. PubMed PMID: 21382422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment. AU - Tota,Santoshkumar, AU - Kamat,Pradeep Kumar, AU - Shukla,Rakesh, AU - Nath,Chandishwar, Y1 - 2011/03/04/ PY - 2011/01/03/received PY - 2011/02/14/revised PY - 2011/02/26/accepted PY - 2011/3/9/entrez PY - 2011/3/9/pubmed PY - 2011/9/7/medline SP - 207 EP - 15 JF - Behavioural brain research JO - Behav Brain Res VL - 221 IS - 1 N2 - 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 (0.5mg/kg), administered twice at an interval of 48h, 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 200mg/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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/21382422/Improvement_of_brain_energy_metabolism_and_cholinergic_functions_contributes_to_the_beneficial_effects_of_silibinin_against_streptozotocin_induced_memory_impairment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(11)00157-4 DB - PRIME DP - Unbound Medicine ER -