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Total Ginsenoside Extract from Panax ginseng Enhances Neural Stem Cell Proliferation and Neuronal Differentiation by Inactivating GSK-3β

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Abstract

Objective

To study the effects of total ginsenosides (TG) extract from Panax ginseng on neural stem cell (NSC) proliferation and differentiation and their underlying mechanisms.

Methods

The migration of NSCs after treatment with various concentrations of TG extract (50, 100, or 200 µ g/mL) were monitored. The proliferation of NSCs was examined by a combination of cell counting kit-8 and neurosphere assays. NSC differentiation mediated by TG extract was evaluated by Western blotting and immunofluorescence staining to monitor the expression of nestin and microtubule associated protein 2 (MAP2). The GSK-3β/β-catenin pathway in TG-treated NSCs was examined by Western blot assay. The NSCs with constitutively active GSK-3β mutant were made by adenovirus-mediated gene transfection, then the proliferation and differentiation of NSCs mediated by TG were further verified.

Results

TG treatment significantly enhanced NSC migration (P<0.01 or P<0.05) and increased the proliferation of NSCs (P<0.01 or P<0.05). TG mediation also significantly upregulated MAP2 expression but downregulated nestin expression (P<0.01 or P<0.05). TG extract also significantly induced GSK-3β phosphorylation at Ser9, leading to GSK-3β inactivation and, consequently, the activation of the GSK-3β/β-catenin pathway (P<0.01 or P<0.05). In addition, constitutive activation of GSK-3β in NSCs by the transfection of GSK-3β S9A mutant was found to significantly suppress TG-mediated NSC proliferation and differentiation (P<0.01 or P<0.05).

Conclusion

TG promoted NSC proliferation and neuronal differentiation by inactivating GSK-3β.

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Authors and Affiliations

  1. School of Public Health, Guangzhou Medical University, Guangzhou, 511436, China

    Kai-li Lin

  2. Department of Biology, Hong Kong Baptist University (HKBU), Hong Kong Special Administrative Region, 999077, China

    Kai-li Lin, Hau-lam Chung, Xin-yi Wu, Stephen Cho-wing Sze, Ken Kin-lam Yung &  Shi-qing Zhang

  3. HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, Guangdong Province, 518057, China

    Kai-li Lin, Stephen Cho-wing Sze, Ken Kin-lam Yung &  Shi-qing Zhang

  4. Department of Plastic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China

    Ji Zhang

  5. Guangzhou Institute of Cardiovascular Disease, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China

    Bin Liu

  6. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Bo-xin Zhao

  7. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China

    Ping-zheng Zhou

Authors
  1. Kai-li Lin
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  2. Ji Zhang
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  3. Hau-lam Chung
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  10. Shi-qing Zhang
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Contributions

Lin KL and Zhang J contributed equally to this work. Lin KL, Zhang J, Chung HL and Wu XY performed the experimental parts; Lin KL, Zhang J, Liu B and Zhao BX performed data analysis; Liu B, Zhao BX and Sze SCW contributed reagents and materials; Lin KL, Zhang J, Yung KKL and Zhang SQ wrote and revised the manuscript; Zhou PZ, Yung KKL and Zhang SQ designed the study; and all authors have read and approved the final manuscript.

Corresponding author

Correspondence to Shi-qing Zhang.

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The authors declare that there are no conflicts of interest.

Additional information

Supported by the National Natural Science Foundation of China (No. 81703728)

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Lin, Kl., Zhang, J., Chung, Hl. et al. Total Ginsenoside Extract from Panax ginseng Enhances Neural Stem Cell Proliferation and Neuronal Differentiation by Inactivating GSK-3β. Chin. J. Integr. Med. 28, 229–235 (2022). https://doi.org/10.1007/s11655-021-3508-1

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  • DOI: https://doi.org/10.1007/s11655-021-3508-1

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