Standardized Extracts of Bacopa monniera Protect Against MPP+- and Paraquat-Induced Toxicity by Modulating Mitochondrial Activities, Proteasomal Functions, and Redox Pathways

Autor: Charles Ramassamy, Ven Murthy, Manjeet Singh
Přispěvatelé: Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Dept Biologie, Université Laval, Université Laval [Québec] (ULaval)
Rok vydání: 2011
Předmět:
MESH: Oxidation-Reduction
1-Methyl-4-phenylpyridinium
MESH: Neurotoxicity Syndromes
Cell Culture Techniques
Mitochondrion
Pharmacology
Toxicology
medicine.disease_cause
Antioxidants
MESH: Dose-Response Relationship
Drug
MESH: Paraquat
chemistry.chemical_compound
MESH: Membrane Potential
Mitochondrial
Paraquat
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
MESH: 1-Methyl-4-phenylpyridinium
Membrane Potential
Mitochondrial
MESH: Glutathione
MESH: Electron Transport Complex I
Superoxide
MESH: Proteasome Endopeptidase Complex
MESH: NF-E2-Related Factor 2
MESH: Reactive Oxygen Species
MESH: Neuroprotective Agents
Glutathione
Mitochondria
Neuroprotective Agents
MESH: Cell Survival
Neurotoxicity Syndromes
Oxidation-Reduction
MESH: Bacopa
Proteasome Endopeptidase Complex
MESH: Cell Line
Tumor
Cell Survival
NF-E2-Related Factor 2
MESH: Mitochondria
MESH: Plant Extracts
Biology
Neuroprotection
Cell Line
Tumor
medicine
Humans
Protein kinase B
MESH: Cell Culture Techniques
Electron Transport Complex I
MESH: Humans
Dose-Response Relationship
Drug
Plant Extracts
MESH: Antioxidants
KEAP1
chemistry
Bacopa
Reactive Oxygen Species
Oxidative stress
Zdroj: Review of Economic Dynamics
Review of Economic Dynamics, Elsevier, 2012, 125 (1), pp.219-32. ⟨10.1093/toxsci/kfr255⟩
ISSN: 1096-0929
1096-6080
1094-2025
DOI: 10.1093/toxsci/kfr255
Popis: Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases and affects millions 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-induced and 1-methyl-4-phenyl-pyridinium iodide (MPP(+))-induced toxicities and to elucidate the mechanisms underlying this protection. Our results show that a pretreatment with the BM extract from 50 μg/ml protected the dopaminergic SK-N-SH cell line against MPP(+)- and PQ-induced toxicities in various cell survival assays. We demonstrate that BM pretreatment prevented the depletion of glutathione (GSH) besides preserving the mitochondrial membrane potential and maintaining the mitochondrial complex I activity. BM pretreatment from 10.0 μg/ml also prevented the generation of intracellular reactive oxygen species and decreased the mitochondrial superoxide level. BM treatment activated the nuclear factor erythroid 2-related factor 2 pathway by modulating the expression of Keap1, thereby upregulating 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 and mitochondrial activities and by promoting cell survival pathways, BM extract may have therapeutic uses in various age-related neurodegenerative diseases such as PD.
Databáze: OpenAIRE
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