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.