TY - JOUR
T1 - Oleanolic acid enhances neural stem cell migration, proliferation, and differentiation in vitro by inhibiting GSK3β activity
AU - Zhang, Shi Qing
AU - Lin, Kai Li
AU - Law, Cheuk Yu
AU - Liu, Bin
AU - Fu, Xiu Qiong
AU - Tse, Wing Sze
AU - Wong, Samantha Sze Man
AU - Sze, Stephen Cho Wing
AU - Yung, Ken Kin Lam
N1 - Funding Information:
This work was financially supported by National Natural Science Foundation of China (NSFC) grants (No. 81703728 and 81774100).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071003736&partnerID=8YFLogxK
U2 - 10.1038/s41420-018-0111-0
DO - 10.1038/s41420-018-0111-0
M3 - Journal article
AN - SCOPUS:85071003736
SN - 2058-7716
VL - 4
JO - Cell Death Discovery
JF - Cell Death Discovery
M1 - 48
ER -
