Spinosin protects N2a cells from H O -induced neurotoxicity through inactivation of p38MAPK.

OBJECTIVES

Previous studies have suggested that spinosin (SPI) exerted neuroprotective effects through inhibition of oxidative damage, but the underlying mechanisms are still unclear. Herein, the mechanisms underlying the protective effects of SPI against oxidative stress induced by hydrogen peroxide (H O ) were examined in neuro-2a (N2a) mouse neuroblastoma cells.

METHODS

N2a cells were pretreated with H O for 2 h, followed by a 24-h incubation with SPI. Intracellular reactive oxygen species (ROS) production was analysed by flow cytometry. Levels of Aβ production were determined by ELISA assay. Levels of expression of c-Jun N-terminal kinase (JNK), p-JNK, extracellular signal-regulated kinase (ERK), p-ERK, p38 mitogen-activated protein kinase (p38MAPK), p-p38MAPK, p-Tau (Ser199), p-Tau (Ser202), p-Tau (Ser396), synaptophysin (SYP) and postsynaptic scaffold postsynaptic density-95 (PSD-95) were detected by Western blot analysis.

KEY FINDINGS

Our results showed that H O treatment enhanced intracellular ROS production in N2a cells. SPI prevented H O -induced oxidative damage via inhibiting Aβ production, decreasing Tau phosphorylation and improving synaptic structural plasticity. Notably, H O -increased p38MAPK activation was attenuated by SPI administration, and p38MAPK inhibitor BIRB796 markedly reduced H O -induced oxidative damage in N2a cells.

CONCLUSIONS

Our findings suggest that SPI protects N2a cells from H O -induced oxidative damage through inactivation of p38MAPK.