Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells.

Abstract

BACKGROUND:

Scopolamine is a well-known cholinergic antagonist that causes amnesia in human and animal models. Scopolamine-induced amnesia in rodent models has been widely used to understand the molecular, biochemical, behavioral changes, and to delineate therapeutic targets of memory impairment. Although this has been linked to the decrease in central cholinergic neuronal activity following the blockade of muscarinic receptors, the underlying molecular and cellular mechanism(s) particularly the effect on neuroplasticity remains elusive. In the present study, we have investigated (i) the effects of scopolamine on the molecules involved in neuronal and glial plasticity both in vivo and in vitro and (ii) their recovery by alcoholic extract of Ashwagandha leaves (i-Extract).

METHODOLOGY/PRINCIPAL FINDINGS:

As a drug model, scopolamine hydrobromide was administered intraperitoneally to mice and its effect on the brain function was determined by molecular analyses. The results showed that the scopolamine caused downregulation of the expression of BDNF and GFAP in dose and time dependent manner, and these effects were markedly attenuated in response to i-Extract treatment. Similar to our observations in animal model system, we found that the scopolamine induced cytotoxicity in IMR32 neuronal and C6 glioma cells. It was associated with downregulation of neuronal cell markers NF-H, MAP2, PSD-95, GAP-43 and glial cell marker GFAP and with upregulation of DNA damage--γH2AX and oxidative stress--ROS markers. Furthermore, these molecules showed recovery when cells were treated with i-Extract or its purified component, withanone.

CONCLUSION:

Our study suggested that besides cholinergic blockade, scopolamine-induced memory loss may be associated with oxidative stress and Ashwagandha i-Extract, and withanone may serve as potential preventive and therapeutic agents for neurodegenerative disorders and hence warrant further molecular analyses.

• Authors: Arpita Konar, Navjot Shah, Rumani Singh, Nishant Saxena, Sunil C Kaul, Renu Wadhwa, Mahendra K Thakur
• Journal: PloS one (PLoS One) Vol. 6 Issue 11 Pg. e27265 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 22096544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• Glial Fibrillary Acidic Protein
• Nerve Tissue Proteins
• Plant Extracts
• Triterpenes
• Withanolides
• glial fibrillary astrocytic protein, mouse
• Scopolamine
• withanone
• Ashwagandha

Topics

• Animals
• Brain (drug effects, metabolism)
• Brain-Derived Neurotrophic Factor (metabolism)
• Cell Line
• Cell Line, Tumor
• DNA Damage (drug effects)
• Glial Fibrillary Acidic Protein
• Mice
• Nerve Tissue Proteins (metabolism)
• Oxidative Stress (drug effects)
• Plant Extracts (pharmacology)
• Plant Leaves (chemistry)
• Scopolamine (toxicity)
• Triterpenes (pharmacology)
• Withania (chemistry)
• Withanolides