Water Extract from the Leaves of Withania somnifera Protect RA Differentiated C6 and IMR-32 Cells against Glutamate-Induced Excitotoxicity

Department of Biotechnology, Guru Nanak Dev University, Amritsar, India.
PLoS ONE (Impact Factor: 3.23). 05/2012; 7(5):e37080. DOI: 10.1371/journal.pone.0037080
Source: PubMed


Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha), also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6) and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty.

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    • "WS is beneficial in children with memory deficit and old age people with memory loss by promoting overall brain functioning (Pingali et al. 2014). Earlier studies have demonstrated the therapeutic potential of WS in induction of neuronal regeneration (Kataria et al. 2012; Chaudhary et al. 2003). WS supplementation has been shown to be effective in improving locomotor and cognitive functions during ageing (Singh et al. 2008). "
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    ABSTRACT: The present study was designed to evaluate the beneficial effects of Withania somnifera (WS) pre-supplementation on middle cerebral artery occlusion (MCAO) model of ischemic stroke. Ischemic stroke was induced in the rats by inserting intraluminal suture for 90 min, followed by reperfusion injury for 24 h. The animals were assessed for locomotor functions (by neurological deficit scores, narrow beam walk and rotarod test), cognitive and anxiety-like behavioural functions (by morris water maze and elevated plus maze test). MCAO animals showed significant impairment in locomotor and cognitive functions. Neurobehavioural changes were accompanied by decreased acetylcholinesterase activity, increased oxidative stress in terms of enhanced lipid peroxidation and lowered thiol levels in the MCAO animals. In addition, MCAO animals had cerebral infarcts and the presence of pycnotic nuclei. Single-photon emission computerized tomography (SPECT) of MCAO animals revealed a cerebral infarct as a hypoactive area. On the other hand, pre-supplementation with WS (300 mg/kg body weight) for 30 days to MCAO animals was effective in restoring the acetylcholinesterase activity, lipid peroxidation, thiols and attenuated MCAO induced behavioural deficits. WS significantly reduced the cerebral infarct volume and ameliorated histopathological alterations. Improved blood flow was observed in the SPECT images from the brain regions of ischemic rats pre-treated with WS. The results of the study showed a protective effect of WS supplementation in ischemic stroke and are suggestive of its potential application in stroke management.
    Full-text · Article · Dec 2015 · Cellular and Molecular Neurobiology
    • "These withanolides have been found cytotoxic to cancer cells, immunomodulatory , and neuroprotective in function (Jayaprakasam et al., 2009; Kuboyama et al., 2005; Llanos et al., 2012; Malik et al., 2007; Maurya, 2010; Mirjalili et al., 2009; Ven Murthy et al., 2010). Among the most recent therapeutic applications of W. somnifera, are the studies in the treatment of various types of cancer (Vyas & Singh, 2014; Winters, 2006), neuroblastomas (Hardeep et al., 2012), breast cancer (Szarc vel Szic et al., 2014; Yang et al., 2013), prostate (Roy et al., 2013), and myeloid cells (Sinha & Rosenberg, 2013). Withania somnifera herbal extracts have shown significant anticancer activity that functions through diverse pathways. "
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    ABSTRACT: Cancer, being a cause of death for major fraction of population worldwide, is one of the most studied diseases and is being investigated for the development of new technologies and more accurate therapies. Still the currently available therapies for cancer have many lacunae which affect the patient's health severely in the form of side effects. The natural drugs obtained from the medicinal plants provide a better alternative to fight against this devastating disease. Withania somnifera L. Dunal (Solanaceae), a well-known Ayurvedic medicinal plant, has been traditionally used to cure various ailments for centuries. Considering the immense potential of W. somnifera, this review provides a detail account of its vital phytoconstituents and summarizes the present status of the research carried out on its anticancerous activities, giving future directions. The sources of scientific literature were accessed from various electronic databases such as PubMed, Google Scholar, Science Direct, and library search. Various parts of W. somnifera especially the roots with its unique contents have been proved effective against different kinds of cancers. The most active components withanolides and withaferins along with a few other metabolites including withanone (WN) and withanosides have been reported effective against different types of cancer cell lines. This herb holds an important place among various anticancer medicinal plants. It is very essential to further screen and to investigate different formulations for anticancer therapy in vitro as well as in vivo in combination with established chemotherapy.
    No preview · Article · Apr 2015 · Pharmaceutical Biology
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    • "In another study, it was demonstrated that W. somnifera root extract and withanolide-A were capable of restoring spatial memory deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission, where W. somnifera reduces the expression of N-metyl-D-aspartate (NMDA) receptor, which is responsible for spatial memory loss in epileptic rats (Soman et al., 2012). Leaf extracts of W. somnifera were also showing its protective action against glutamate induced toxicity in human neuroblastoma (IMR-32) cells, by inhibiting over expression of stress protein 70 kilodalton heat shock proteins (Kataria et al., 2012). In another study it was found that W. somnifera root extract and withanolide-A regulate the expression and function of α-Amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptor and glutamate levels in brain dopaminergic nervous system and results are attributed to improvement in motor learning in pilocarpine-induced temporal lobe epilepsy model (Soman et al., 2013). "
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