| Standardized extracts of Bacopa monniera protect against MPP+ and Paraquat induced- toxicities by modulating mitochondrial activities, proteasomal functions and redox pathways. | |
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MedLine Citation:
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PMID: 21972102 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Parkinson's disease (PD) is one of the most common age related neurodegenerative diseases and affects million of people worldwide. Strong evidence supports the role of free radicals, oxidative stress, mitochondrial and proteasomal dysfunctions underlying neuronal death in PD. Environmental factors especially, pesticides represent one of the primary classes of neurotoxic agents associated with PD and several epidemiological studies have identified the exposure of the herbicide paraquat (PQ) as a potential risk factor for the onset of PD. The objective of our study was to investigate the neuroprotective effects of the standardized extracts of Bacopa monniera (BM) against PQ and MPP(+) induced toxicity and to elucidate the mechanisms underlying this protection. Our results show that a pre-treatment with the BM extract from 50 μg/ml protected the dopaminergic SK-N-SH cell line against MPP(+) and PQ-induced toxicity in various cell survival assays. We demonstrate that BM pre-treatment prevented the depletion of GSH besides preserving the mitochondrial membrane potential and maintaining the mitochondrial complex I activity. BM pre-treatment from 10.0 μg/ml also prevented the generation of intracellular reactive oxygen species (ROS) and decreased the mitochondrial superoxide level. BM treatment activated the nuclear factor E2-related factor2 (Nrf2) pathway by modulating the expression of Keap1 thereby up-regulating the endogenous GSH synthesis. The effect of BM on the phosphorylation of Akt further strengthens its role in the promotion of cell survival. By preserving the cellular redox homeostasis, mitochondrial activities, and by promoting cell survival pathways, BM extract may have therapeutic uses in various age related neurodegenerative diseases such as PD. |
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Authors:
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Manjeet Singh; Ven Murthy; Charles Ramassamy |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-4 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: - ISSN: 1096-0929 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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INRS- Institut Armand Frappier. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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