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Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective

BACKGROUND: Glutamate, the major excitatory neurotransmitter of CNS acts as a neurotoxin at higher concentrations. Prolonged activation of glutamate receptors results in progressive neuronal damage by aggravating calcium influx, inducing mitochondrial damage and oxidative stress. Excitotoxic cell de...

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Autores principales: Sharma, Anuradha, Kaur, Gurcharan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167833/
https://www.ncbi.nlm.nih.gov/pubmed/30285727
http://dx.doi.org/10.1186/s12906-018-2330-6
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author Sharma, Anuradha
Kaur, Gurcharan
author_facet Sharma, Anuradha
Kaur, Gurcharan
author_sort Sharma, Anuradha
collection PubMed
description BACKGROUND: Glutamate, the major excitatory neurotransmitter of CNS acts as a neurotoxin at higher concentrations. Prolonged activation of glutamate receptors results in progressive neuronal damage by aggravating calcium influx, inducing mitochondrial damage and oxidative stress. Excitotoxic cell death is associated with the pathogenesis of various neurodegenerative disorders such as trauma, brain injury and neurodegenerative diseases. The current study was designed to investigate the neuroprotective and neuroregenerative potential of Tinospora cordifolia against glutamate-induced excitotoxicity using primary cerebellar neuronal cultures as a model system. METHODS: Monosodium salt of glutamate was used to induce neurotoxic injury in primary cerebellar neurons. Four extracts including Hexane extract, Chloroform extract, Ethyl acetate, and Butanol extract were obtained from fractionation of previously reported aqueous ethanolic extract of T. cordifolia and tested for neuroprotective activity. Out of the four fractions, Butanol extract of T. cordifolia (B-TCE) exhibited neuroprotective potential by preventing degeneration of neurons induced by glutamate. Expression of different neuronal, apoptotic, inflammatory, cell cycle regulatory and plasticity markers was studied by immunostaining and Western blotting. Neurite outgrowth and migration were also studied using primary explant cultures, wound scratch and gelatin zymogram assay. RESULTS: At molecular level, B-TCE pretreatment of glutamate-treated cultures normalized the stress-induced downregulation in the expression of neuronal markers (MAP-2, GAP-43, NF200) and anti-apoptotic marker (Bcl-xL). Further, cells exposed to glutamate showed enhanced expression of inflammatory (NF-κB, AP-1) and senescence markers (HSP70, Mortalin) as well as the extent of mitochondrial damage. However, B-TCE pretreatment prevented this increase and inhibited glutamate-induced onset of inflammation, stress and mitochondrial membrane damage. Furthermore, B-TCE was observed to promote regeneration, migration and plasticity of cerebellar neurons, which was otherwise significantly inhibited by glutamate treatment. CONCLUSION: These results suggest that B-TCE may have neuroprotective and neuroregenerative potential against catastrophic consequences of glutamate-mediated excitotoxicity and could be a potential therapeutic candidate for neurodegenerative diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12906-018-2330-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-61678332018-10-09 Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective Sharma, Anuradha Kaur, Gurcharan BMC Complement Altern Med Research Article BACKGROUND: Glutamate, the major excitatory neurotransmitter of CNS acts as a neurotoxin at higher concentrations. Prolonged activation of glutamate receptors results in progressive neuronal damage by aggravating calcium influx, inducing mitochondrial damage and oxidative stress. Excitotoxic cell death is associated with the pathogenesis of various neurodegenerative disorders such as trauma, brain injury and neurodegenerative diseases. The current study was designed to investigate the neuroprotective and neuroregenerative potential of Tinospora cordifolia against glutamate-induced excitotoxicity using primary cerebellar neuronal cultures as a model system. METHODS: Monosodium salt of glutamate was used to induce neurotoxic injury in primary cerebellar neurons. Four extracts including Hexane extract, Chloroform extract, Ethyl acetate, and Butanol extract were obtained from fractionation of previously reported aqueous ethanolic extract of T. cordifolia and tested for neuroprotective activity. Out of the four fractions, Butanol extract of T. cordifolia (B-TCE) exhibited neuroprotective potential by preventing degeneration of neurons induced by glutamate. Expression of different neuronal, apoptotic, inflammatory, cell cycle regulatory and plasticity markers was studied by immunostaining and Western blotting. Neurite outgrowth and migration were also studied using primary explant cultures, wound scratch and gelatin zymogram assay. RESULTS: At molecular level, B-TCE pretreatment of glutamate-treated cultures normalized the stress-induced downregulation in the expression of neuronal markers (MAP-2, GAP-43, NF200) and anti-apoptotic marker (Bcl-xL). Further, cells exposed to glutamate showed enhanced expression of inflammatory (NF-κB, AP-1) and senescence markers (HSP70, Mortalin) as well as the extent of mitochondrial damage. However, B-TCE pretreatment prevented this increase and inhibited glutamate-induced onset of inflammation, stress and mitochondrial membrane damage. Furthermore, B-TCE was observed to promote regeneration, migration and plasticity of cerebellar neurons, which was otherwise significantly inhibited by glutamate treatment. CONCLUSION: These results suggest that B-TCE may have neuroprotective and neuroregenerative potential against catastrophic consequences of glutamate-mediated excitotoxicity and could be a potential therapeutic candidate for neurodegenerative diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12906-018-2330-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-01 /pmc/articles/PMC6167833/ /pubmed/30285727 http://dx.doi.org/10.1186/s12906-018-2330-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sharma, Anuradha
Kaur, Gurcharan
Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective
title Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective
title_full Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective
title_fullStr Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective
title_full_unstemmed Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective
title_short Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective
title_sort tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167833/
https://www.ncbi.nlm.nih.gov/pubmed/30285727
http://dx.doi.org/10.1186/s12906-018-2330-6
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