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Effect of Withania somnifera Supplementation on Rotenone-Induced Oxidative Damage in Cerebellum and Striatum of the Male Mice Brain

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Title Effect of Withania somnifera Supplementation on Rotenone-Induced
Oxidative Damage in Cerebellum and Striatum of the Male Mice Brain
 
Creator Manjunath, M. J.
Dr., Muralidhara
 
Subject 09 Human Physiology
04 Medicinal Plants
 
Description Withania somnifera (WS) an ayurvedic medicinal herb is widely known for its memory enhancing ability and
improvement of brain function. In the present study, we tested the hypothesis that WS prophylaxis could offset
neurotoxicant-induced oxidative dysfunctions in developing brain employing a rotenone (ROT) mouse model. Initially,
we assessed the potential of WS oral supplements (100-400 mg/ kg b.w/ d, 4wks) to modulate the endogenous levels of
oxidative markers in cerebellum (cb) and striatum (st) of prepubertal (PP) mice. Further, we assessed the induction of
oxidative stress in cb and st of mice administered with ROT (i.p. 0.5 and 1mg/ kg b.w, 7d). ROT caused significant
elevation in the levels of reactive oxygen species (ROS), malondialdehyde (MDA), hydroperoxides (HP) and nitric oxide
(NO) levels in both brain regions. Further ROT caused significant perturbations in the levels of reduced glutathione
(GSH), activity levels of antioxidant enzymes, acetylcholinesterase and mitochondrial dysfunctions suggesting a state of
oxidative stress. In a satellite study, we examined the protective effects of WS root powder (400mg/ kg b.w/ d, 4wks) in
PP mice challenged with ROT (0.5 mg/ kg b.w/ d, 7 d). WS prophylaxis significantly offset ROT-induced oxidative
damage in st and cb as evident by the normalized levels of oxidative markers (MDA, ROS levels and HP) and restoration
of depleted GSH levels. Further, WS effectively normalized the NO levels in both brain regions suggesting its antiinflammatory
action. Furthermore, WS prophylaxis restored the activity levels of cytosolic antioxidant enzymes,
neurotransmitter function and dopamine levels in st. Taken together, these findings suggest that WS prophylaxis has the
propensity to modulate neurotoxicant-mediated oxidative impairments and mitochondrial dysfunctions in specific brain
regions of mice. While the exact mechanism/s underlying the neuroprotective effects of WS merit further investigation,
based on our findings, we hypothesize that it may be wholly or in part due to its ability to enhance GSH, thiols and
antioxidant defences in the brain of mice.
 
Date 2013
 
Type Article
PeerReviewed
 
Format application/pdf
 
Language en
 
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Identifier http://ir.cftri.com/12191/1/Central%20Nervous%20System%20Agents%20in%20Medicinal%20Chemistry%2C%202013%2C%2013%2C%2043-56.pdf
Manjunath, M. J. and Dr., Muralidhara (2013) Effect of Withania somnifera Supplementation on Rotenone-Induced Oxidative Damage in Cerebellum and Striatum of the Male Mice Brain. Central Nervous System Agents in Medicinal Chemistry, 13. pp. 43-56.