Zhang Shi Qing, Lin Kai Li, Law Cheuk Yu, Liu Bin, Fu Xiu Qiong, Tse Wing Sze, Wong Samantha Sze Man, Sze Stephen Cho Wing, Yung Ken Kin Lam
1Faculty of Science, Department of Biology, Hong Kong Baptist University (HKBU), Hong Kong, China.
HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China.
Cell Death Discov. 2018 Oct 15;4:48. doi: 10.1038/s41420-018-0111-0. eCollection 2018.
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.
齐墩果酸（OA）是人参中的生物活性成分之一，据报道具有神经保护活性。然而，其对神经干细胞（NSC）诱导的作用及其机制尚不完全清楚。在本研究中，我们研究了OA对促进神经干细胞（NSCs）迁移、增殖和分化的影响。分别使用神经特异性标记物、神经球测定法和细胞计数试剂盒-8来研究迁移和增殖。我们发现OA以时间和剂量依赖性方式显著促进NSCs的神经迁移和增殖。通过蛋白质免疫印迹法和免疫荧光染色分析分化情况，结果发现微管相关蛋白2（MAP2）表达显著增加，而巢蛋白（Nestin）显著减少。此外，OA增加了糖原合成酶激酶3β（GSK3β）在丝氨酸9位点的磷酸化以及β-连环蛋白活性形式的表达。此外，组成型激活的GSK3β（S9A）的NSCs显著抑制了OA诱导的增殖和神经分化。这些结果表明，OA可通过抑制GSK3β的活性在体外刺激NSC增殖和神经分化。我们的研究结果可能对神经退行性疾病的治疗具有重要意义。
