Ginsenoside metabolite 20(S)-protopanaxadiol promotes neural stem cell transition from a state of proliferation to differentiation by inducing autophagy and cell cycle arrest
Ginsenoside metabolite 20(S)-protopanaxadiol promotes neural stem cell transition from a state of proliferation to differentiation by inducing autophagy and cell cycle arrest
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人参皂苷代谢物20(S)-原人参二醇通过诱导自噬和细胞周期阻滞促进神经干细胞从增殖状态向分化状态转变
DOI：
10.3892/mmr.2020.11081
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发表时间：
2020-07-01
影响因子：
3.4
通讯作者：
Luo, Zhiyong
中科院分区：
文献类型：
--
作者：
Chen, Shali;He, Ji;Luo, Zhiyong
20（S）-原人参二醇（PPD）是人参的活性代谢物，是原人参二醇皂苷经人体肠道菌群代谢的最终形式。PPD对神经干细胞的神经保护作用及其机制尚不完全清楚。本研究的目的是评估PPD对神经干细胞增殖和分化的影响。在本研究中，用不同浓度的PPD处理24 h后，BrdU阳性细胞的百分比随着PPD浓度的增加而显著降低。流式细胞仪分析结果显示，PPD处理后G 0/G1期和G2/M期细胞比例增加，S期细胞比例减少。通过自噬空泡数量增加和轻链3脂质化确定的自噬激活与PPD处理后神经元标记物微管蛋白-β3表达增加相关。PPD还部分地从自噬抑制剂渥曼青霉素的抑制作用中拯救了NSC，这表明PPD对NSC分化的作用与自噬相关。总之，结果表明PPD通过诱导自噬和细胞周期阻滞促进神经干细胞从增殖状态向分化状态的转变。因此，本研究可能为基于已批准的安全药物的再生疗法的开发提供基础。
20(S)-Protopanaxadiol (PPD) is an active ginseng metabolite and is the final form of protopanaxadiol saponins metabolized by human intestinal microflora. The neuroprotective effects and mechanisms underlying PPD on neural stem cells (NSCs) are not completely understood. The aim of the present study was to assess the effects of PPD on the proliferation and differentiation of neural stem cells. In the present study, following treatment with different concentrations of PPD for 24 h, the percentage of BrdU-positive cells decreased significantly with increasing concentrations of PPD. Moreover, flow cytometric analysis results indicated that PPD treatment increased the proportion of cells in the G0/G1 and G2/M phase and decreased the proportion of cells in the S phase. The activation of autophagy, determined by an increased number of autophagic vacuoles and light chain 3 lipidation, was associated with an increase in the expression of the neuronal marker tubulin-β3 following PPD treatment. PPD also partially rescued NSCs from the inhibitory effects of the autophagic inhibitor wortmannin, suggesting that the effect of PPD on NSC differentiation was associated with autophagy. Collectively, the results indicated that PPD promoted the transition of NSCs from a state of proliferation to differentiation through the induction of autophagy and cell cycle arrest. Therefore, the present study may provide a basis for the development of regenerative therapies based on ginsenoside, an approved and safe drug.