Spinosin protects N2a cells from H2O2-induced neurotoxicity through inactivation of p38MAPK

Abstract

Abstract 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 (H2O2) were examined in neuro-2a (N2a) mouse neuroblastoma cells. Methods N2a cells were pretreated with H2O2 for 2 h, followed by a 24-h incubation with SPI. Intracellular reactive oxygen species (ROS) production was analysed by flow cytometry. Levels of Aβ1-42 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 H2O2 treatment enhanced intracellular ROS production in N2a cells. SPI prevented H2O2-induced oxidative damage via inhibiting Aβ1-42 production, decreasing Tau phosphorylation and improving synaptic structural plasticity. Notably, H2O2-increased p38MAPK activation was attenuated by SPI administration, and p38MAPK inhibitor BIRB796 markedly reduced H2O2-induced oxidative damage in N2a cells. Conclusions Our findings suggest that SPI protects N2a cells from H2O2-induced oxidative damage through inactivation of p38MAPK.