Modulation of hydrogen peroxide and acrolein-induced oxidative stress, mitochondrial dysfunctions and redox regulated pathways by the Bacopa monniera extract: potential implication in Alzheimer's disease.
Acrolein is one of the by-products of lipid peroxidation. Due to its high reactivity, it is not only a marker of lipid peroxidation but could also be an initiator of oxidative stress by adducting cellular nucleophilic groups. In brains of Alzheimer's disease (AD) patients, levels of acrolein are significantly higher in vulnerable brain region and, on primary hippocampal culture, it is more toxic than 4-hydroxyl-nonenal. The toxicity of the amyloid-beta peptide is mediated through the generation of hydrogen peroxide (H2O2). The actions of H2O2 include oxidative modifications of proteins, lipids, and DNA as observed in AD. Bacopa monniera (BM) has a long history of use in India as a memory-enhancing therapy. The objective of our study was to investigate the neuroprotective effects of the standardized extracts of BM against acrolein and H2O2 and to elucidate the mechanisms underlying this protection. Our results show that a pre-treatment with the BM extract protected the human neuroblastoma cell line SK-N-SH against H2O2 and acrolein. We demonstrated that BM pre-treatment significantly inhibited the generation of intracellular reactive oxygen species in addition to preserving the mitochondrial membrane potential. BM pre-treatment also prevented the modifications of the activity of several redox regulated proteins, i.e., NF-kappaB, Sirt1, ERK1/2, and p66Shc, so as to favor cell survival in response to oxidative stress. Thus, our findings demonstrate that BM can protect human neuroblastoma cells against H2O2 and acrolein through different mechanisms involved in the pathophysiology of AD and could have a therapeutic application in the prevention of AD.
Singh
Manjeet
M
INRS-Institut Armand Frappier, Laval, PQ, Canada.
Murthy
Ven
V
Ramassamy
Charles
C
D000171:Acrolein / Q000494:pharmacology*; D034681:Bacopa / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042967:Electron Transport Complex I / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009447:Neuroblastoma / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D010936:Plant Extracts; D017382:Reactive Oxygen Species; D000171:Acrolein; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D042967:Electron Transport Complex I; D005978:Glutathione