20(S)-protopanaxadiol promotes the migration, proliferation, and differentiation of neural stem cells by targeting GSK-3 in the Wnt/GSK-3 / -catenin pathway

• Published in: Journal of ginseng research 2020, 44(3), , pp.475-482
• Main Authors: Kaili Lin, Bin Liu, Sze-Lam Lim, Xiuqiong Fu, Stephen C.-W. Sze(Kowloon Tong, Hong Kong Special Administrative Region, Ken K.-L. Yung(Hong Kong Baptist University, Shiqing Zhang(Kowloon Tong, Hong Kong Special Administrative Region
• Format: Article
• Language: English
• Subjects: 기타의약학
• ISSN: 1226-8453; 2093-4947
• DOI: 10.1016/j.jgr.2019.03.001

Background: Active natural ingredients, especially small molecules, have recently received wide attentionas modifiers used to treat neurodegenerative disease by promoting neurogenic regeneration ofneural stem cell (NSC) in situ. 20(S)-protopanaxadiol (PPD), one of the bioactive ingredients in ginseng,possesses neuroprotective properties. However, the effect of PPD on NSC proliferation and differentiationand its mechanism of action are incompletely understood. Methods: In this study, we investigated the impact of PPD on NSC proliferation and neuronal lineagedifferentiation through activation of the Wnt/glycogen synthase kinase (GSK)-3b/b-catenin pathway. NSCmigration and proliferation were investigated by neurosphere assay, Cell Counting Kit-8 assay, and EdUassay. NSC differentiation was analyzed by Western blot and immunofluorescence staining. Involvementof the Wnt/GSK3b/b-catenin pathway was examined by molecular simulation and Western blot andverified using gene transfection. Results: PPD significantly promoted neural migration and induced a significant increase inNSC proliferation in a time- and dose-dependent manner. Furthermore, a remarkable increase in antimicrotubule-associated protein 2 expression and decrease in nestin protein expression were induced byPPD. During the differentiation process, PPD targeted and stimulated the phosphorylation of GSK-3b atSer9 and the active forms of b-catenin, resulting in activation of the Wnt/GSK-3b/b-catenin pathway. Transfection of NSCs with a constitutively active GSK-3b mutant at S9A significantly hampered theproliferation and neural differentiation mediated by PPD. Conclusion: PPD promotes NSC proliferation and neural differentiation in vitro via activation of the Wnt/GSK-3b/b-catenin pathway by targeting GSK-3b, potentially having great significance for the treatment ofneurodegenerative diseases. KCI Citation Count: 9