Protective Effects of L-3-n-Butylphthalide Against H2O2-Induced Injury in Neural Stem Cells by Activation of PI3K/Akt and Mash1 Pathway

Abstract

It has been reported that oxidative stress could result in damage to the developing brain. L-3-n-butylphthalide (L-NBP) could inhibit neuronal cell apoptosis and has neurogenesis effect in different animal and cellular models. However, whether L-NBP could protect the process of neurogenesis in neural stem cells (NSCs) against oxidative stress injury is still unclear. Here, in the present study, we evaluated the neuroprotective effect of L-NBP in NSCs against H2O2-induced injury and the possible mechanisms. The results showed that L-NBP elevated the proliferation of NSCs by upregulating cyclin D1, and PI3K/Akt might be a possible target in this process. Subsequently, L-NBP was found to promote the migration of NSCs and N-cadherin might be involved in. NSC differentiation was measured using immunofluorescence staining and the results demonstrated that L-NBP could promote the NSCs to differentiate more into neurons. The elevation of achaete–scute homolog1 (Mash1) expression might be a key factor as attenuation of endogenous Mash1 expression by short-interfering RNA could block L-NBP-promoted neuronal differentiation. In summary, L-NBP exerts protective effects in NSCs against H2O2-induced injury by promoting the proliferation, migration and neural differentiation of NSCs, indicating that L-NBP might be a potential therapeutic agent for the neurogenesis-based treatment for some brain diseases, such as Alzheimer’s disease (AD).