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.