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Oleanolic acid enhances neural stem cell migration proliferation and differentiation in vitro by inhibiting GSK3β activity

机译:齐墩果酸通过抑制GSK3β活性增强神经干细胞在体外的迁移增殖和分化

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摘要

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.
机译:齐墩果酸(OA)是人参中的一种生物活性成分,据报道具有神经保护活性。但是,对神经干细胞(NSC)诱导的影响及其机制尚不完全清楚。在本研究中,我们调查了OA对促进神经干细胞(NSCs)迁移,增殖和分化的影响。分别通过使用神经特异性标记物,神经球测定法和Cell Counting Kit-8研究了迁移和增殖。我们发现OA以时间和剂量依赖性方式显着促进了NSC的神经迁移和增殖。通过蛋白质印迹和免疫荧光染色分析分化,发现MAP2表达显着增加,而Nestin显着减少。此外,OA增加了Ser9处GSK3β的磷酸化和β-catenin活性形式的表达。此外,具有组成性活性GSK3β(S9A)的NSC显着抑制OA诱导的增殖和神经分化。这些结果表明,OA可以通过抑制GSK3β的活性来刺激NSC的增殖和神经分化。我们的发现可能对神经退行性疾病的治疗具有重要意义。

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