N6-(2-hydroxyethyl)-adenosine from Cordyceps cicadae attenuates hydrogen peroxide induced oxidative toxicity in PC12 cells.

N6-(2-hydroxyethyl)-adenosine (HEA), is one of the active molecule found in Cordyceps cicadae. The protective effect of HEA against H2O2 induced oxidative damage in PC12 cells and the mechanism of action was investigated. The cells were exposed to varying concentrations of HEA (5-40 μM) for a period of 24 h and further incubated with 100 μM of H2O2 for an another 12 h. Cell viability, LDH release, MMP collapse, Ca2+ overload, antioxidant parameters (reactive oxygen species generation (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), inflammatory mediators (interleukins 6 and 1β (IL-6 and IL-1β), tumor necrosis factor alpha (TNF-α) and NF-kB were evaluated. The results obtained showed that cells exposed to H2O2 toxicity showed reduced cell viability, increased LDH, ROS and Ca2+ overload. However, prior treatment of PC12 cells with HEA increased cell viability, reduced LDH release, MMP collapse, Ca2+ overload and ROS generation induced by H2O2 toxicity. Furthermore, HEA also increased the activities of antioxidant enzymes and inhibited lipid peroxidation as well as reduced IL-6, IL-1β, TNF-α and NF-kB. Thus, our results provided insight into the attenuative effect of HEA against H2O2 induced cell death through its antioxidant action by reducing ROS generation, oxidative stress and protecting mitochondrial function.