Abstract
Oleanolic acid (OA), one of the bioactive ingredients in ginseng, has been reported to have neuroprotective activities. However, the effects and its mechanism on neural stem cell (NSC) induction are not entirely clear. In the present study, we investigated the effects of OA on promoting the migration, proliferation, and differentiation of neural stem cells (NSCs). Migration and proliferation were investigated by using neural-specific markers, neurosphere assay, and Cell Counting Kit-8, respectively. We found OA remarkably promoted neural migration and proliferation of NSCs in a time- and dose-dependent manner. Differentiation was analyzed by western blotting and immunofluorescence staining, which found MAP2 expression was remarkably increased, whereas Nestin was dramatically decreased. In addition, OA increased phosphorylation of GSK3β at Ser9 and expression of active forms of β-catenin. Furthermore, NSCs with constitutively active GSK3β (S9A) significantly suppressed the OA-induced proliferation and neural differentiation. These results showed that OA could stimulate NSC proliferation and neural differentiation in vitro via suppressing the activity of GSK3β. Our findings may have significant implications for the treatment of neurodegenerative diseases.
Highlights
Oleanolic acid (OA), one of the key bioactive ingredients of ginseng, is a triterpenoid compound that possess pharmacological properties including neuroprotective[1], anti-cancer, and anti-inflammatory activities[2]
We investigated the effects of OA on neural stem cell (NSC) proliferation and neural differentiation
These results indicate that OA can significantly promote NSC proliferation and self-renewal in vitro
Summary
Oleanolic acid (OA), one of the key bioactive ingredients of ginseng, is a triterpenoid compound that possess pharmacological properties including neuroprotective[1], anti-cancer, and anti-inflammatory activities[2]. The main pathogenesis of neurodegenerative disease is the progressive loss of function or death of neurons[5]. One promising therapeutic approach for treating neurodegenerative diseases is neuron transplantation or inducing the neurogenic differentiation of NSCs in situ[6]. NSCs have limited ability to self-renew and differentiate into neurons, astrocytes, and oligodendrocytes under normal conditions[7], and require induction by growth factors (GFs). It was reported that residual GFs may increase the risk of developing a tumor after transplantation[8]. Greater attention has been paid to the development of active ingredients extracted from natural medicines that can promote NSC proliferation and neural
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