| Elevated levels of reactive oxygen species (ROS) have been implicated in the pathogenesis of many diseases. Recent studies suggest beneficial effects, and increased overall health, are associated with consumption of foods rich in polyphenols such as fruits, wines and teas. Further, studies demonstrate that polyphenols, specifically epigallocatechin gallate (EGCG) act as potent scavengers, metal chelators and regulators of survival genes, and may promote survival in oxidatively stressed cells by reducing intracellular levels of ROS and inhibiting key steps in the apoptotic pathway. In light of this research, polyphenols have been proven successful in treating and delaying the onset of neurodegenerative disorders such as Parkinson's disease. In an effort to better understand beneficial properties of polyphenols in oxidative stress conditions, the aim of this study was to screen 12 polyphenols for their ability to increase viability of PC12 cells stressed via cobalt chloride (CoCl 2) or hydrogen peroxide (H2O2). Further, to better understand protective mechanisms, the neuroprotective effects of polyphenols showing increased viability under stressed conditions were investigated in PC12 cells subjected to H2O2-induced apoptosis.;Cell viability data presented here demonstrates that methyl gallate (MG) was the only polyphenol to exert protective effects under H2O 2 stressed conditions. Although EGCG did not demonstrate the ability to increase survival of stressed cells, EGCG, MG and gallic acid (GA) proved beneficial in reducing intracellular levels of CoCl2-derived ROS. Quantitation of apoptosis and mitochondrial membrane potential shows that MG pre-treatment prevents mitochondrial depolarization however does not inhibit apoptosis. Analysis of DNA degradation and caspase activation demonstrate that MG inhibits activation of caspase 9 and has a partial inhibitory effect on DNA degradation, suggesting involvement of the death receptor-mediated pathway. These findings suggest that MG may possess beneficial properties against ROS associated diseases and oxidative stress-induced apoptosis. |
