人参总皂苷通过抑制GSK-3β活性促进神经干细胞增殖及分化为神经元

Kai-li LIN; Ji ZHANG; Hau-lam CHUNG; Xin-yi WU; Bin LIU; Bo-xin ZHAO; Stephen Cho-wing SZE; Ping-zheng ZHOU; Ken Kin-lam YUNG; Shi-qing ZHANG

doi:10.1007/s11655-021-3508-1

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人参总皂苷通过抑制GSK-3β活性促进神经干细胞增殖及分化为神经元

Original Article | Updated：2022-03-18

- 人参总皂苷通过抑制GSK-3β活性促进神经干细胞增殖及分化为神经元
- Total Ginsenoside Extract from Panax ginseng Enhances Neural Stem Cell Proliferation and Neuronal Differentiation by Inactivating GSK-3β
- Chinese Journal of Integrative Medicine 2022年28卷第3期页码：229-235
- Affiliations：
  
  1.School of Public Health, Guangzhou Medical University,Guangzhou (511436), China
  2.Department of Biology, Hong Kong Baptist University (HKBU), Hong Kong Special Administrative Region (999077), China
  3.HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, Guangdong Province(518057), China
  4.Department of Plastic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou (510515),China
  5.Guangzhou Institute of Cardiovascular Disease, the Second Affiliated Hospital of Guangzhou Medical University,Guangzhou (510260), China
  6.Department of Pharmacy,Nanfang Hospital, Southern Medical University, Guangzhou(510515), China
  7.Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou (510515), China
- Author bio：
  
  Dr. ZHANG Shi-qing, E-mail: shiqingzhang@hkbu.edu.hk
- Funds：
  
  the National Natural Science Foundation of China(81703728)
- DOI：10.1007/s11655-021-3508-1
  中图分类号：
- 纸质出版日期：2022-03-01，
  
  网络出版日期：2022-01-27，
  
  录用日期：2021-02-15
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Kai-li LIN, Ji ZHANG, Hau-lam CHUNG, 等. 人参总皂苷通过抑制GSK-3β活性促进神经干细胞增殖及分化为神经元[J]. Chinese Journal of Integrative Medicine, 2022,28(3):229-235.

Kai-li LIN, Ji ZHANG, Hau-lam CHUNG, et al. Total Ginsenoside Extract from Panax ginseng Enhances Neural Stem Cell Proliferation and Neuronal Differentiation by Inactivating GSK-3β[J]. Chinese Journal of Integrative Medicine, 2022,28(3):229-235.
Kai-li LIN, Ji ZHANG, Hau-lam CHUNG, 等. 人参总皂苷通过抑制GSK-3β活性促进神经干细胞增殖及分化为神经元[J]. Chinese Journal of Integrative Medicine, 2022,28(3):229-235. DOI： 10.1007/s11655-021-3508-1.

Kai-li LIN, Ji ZHANG, Hau-lam CHUNG, et al. Total Ginsenoside Extract from Panax ginseng Enhances Neural Stem Cell Proliferation and Neuronal Differentiation by Inactivating GSK-3β[J]. Chinese Journal of Integrative Medicine, 2022,28(3):229-235. DOI： 10.1007/s11655-021-3508-1.

摘要

目的:

研究人参提取的总皂苷 (TG) 对神经干细胞 (NSC) 增殖和分化的影响及作用机制.

方法:

不同浓度的TG (50、100或200 μg/mL) 处理NSC后

检测NSC迁移

用CCK-8和神经球实验检测TG诱导的NSC增殖; 通过Western blot和免疫荧光染色法检测nestin和MAP2蛋白表达评估TG对NSC分化的影响; Western blot检测TG处理后NSC中GSK-3β/β-catenin通路活性. 腺病毒转染构建GSK-3β持续激活型NSC

并检测TG对其增殖和分化的影响.

结果:

TG促进NSC的迁移 (

0.01或

0.05) 和增殖 (

0.01或

0.05) ; TG使NSC中MAP2蛋白表达增加、nestin蛋白表达降低 (

0.01或

0.05) ; TG促进GSK-3β在Ser9位点的磷酸化使GSK-3β失活

从而激活了GSK-3β/β-catenin途径 (

0.01或

0.05) . 此外

转染GSK-3β S9A构建GSK-3β持续激活型的NSC可以抵抗TG促NSC增殖和分化的作用 (

0.01或

0.05) .

结论:

TG通过抑制GSK-3β活性促进NSC增殖和分化为神经元.

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 μg/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 (

0.01 or

0.05) and increased the proliferation of NSCs (

0.01 or

0.05). TG mediation also significantly upregulated MAP2 expression but downregulated nestin expression (

0.01 or

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 (

0.01 or

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 (

0.01 or

0.05).

Conclusion:

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

关键词

Keywords

ginsenosideneural stem cellproliferationneuronal differentiationGSK-3β

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