Ginsenoside Rg1 protects against neurodegeneration by inducing neurite outgrowth in cultured hippocampal neurons.
Ginsenoside Rg1 protects against neurodegeneration by inducing neurite outgrowth in cultured hippocampal neurons.
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人参皂苷 Rg1 通过诱导培养的海马神经元神经突生长来防止神经退行性变
DOI：
10.4103/1673-5374.177741
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发表时间：
2016-02
影响因子：
6.1
通讯作者：
Yuan QL
中科院分区：
文献类型：
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作者：
Huang L;Liu LF;Liu J;Dou L;Wang GY;Liu XQ;Yuan QL
人参皂苷Rg1具有抗衰老和抗神经退行性变的作用。然而，这些行动背后的机制仍不清楚。本研究的目的是确定Rg1在体外暴露于淀粉样β蛋白片段25-35(A？25-35)后是否影响海马存活和突起生长，并探讨细胞外信号调节激酶(ERK)和Akt信号转导通路是否参与这些生物学过程。我们培养新生大鼠的海马神经元24小时，然后在培养液中加入Rg1，再加或不加丝裂原活化蛋白激酶(MAPK)家族或Akt信号通路的药物抑制剂再加24小时。然后，我们对神经元进行生长相关蛋白-43的免疫组织化学染色，并测量轴突长度。在另一项单独的实验中，我们将培养的海马神经元暴露在Aü25-35中30分钟，然后加入Rg1 48小时，使用或不使用Akt或MAPK抑制剂，并用Hoechst 33258染色和Western印迹分析评估神经元存活和ERK1/2和Akt的磷酸化。Rg1诱导的轴突生长可被API2(Akt抑制剂)和PD98059(MAPK/ERK激酶抑制剂)阻断，但不能被c-jun氨基末端激酶和p38MAPK抑制剂SP600125或SB203580阻断。与此作用一致的是，Rg1上调Akt和ERK1/2的磷酸化；这些作用分别被API-2和PD98059逆转。此外，Rg1还能显著逆转A？25-35诱导的细胞凋亡，这一作用可被API-2和PD98059阻断，但不能被SP600125或SB203580阻断。最后，Rg1显著逆转了Aü25-35诱导的Akt和ERK1/2磷酸化水平的降低，但API-2阻止了这一逆转。我们的结果表明，Rg1促进了突起的生长，并对Aü25-35诱导的损伤具有保护作用，其机制可能与激活Akt和ERK1/2信号有关。
Ginsenoside Rg1 (Rg1) has anti-aging and anti-neurodegenerative effects. However, the mechanisms underlying these actions remain unclear. The aim of the present study was to determine whether Rg1 affects hippocampal survival and neurite outgrowth in vitro after exposure to amyloid-beta peptide fragment 25-35 (Aß25-35 ), and to explore whether the extracellular signal-regulated kinase (ERK) and Akt signaling pathways are involved in these biological processes. We cultured hippocampal neurons from newborn rats for 24 hours, then added Rg1 to the medium for another 24 hours, with or without pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) family or Akt signaling pathways for a further 24 hours. We then immunostained the neurons for growth associated protein-43, and measured neurite length. In a separate experiment, we exposed cultured hippocampal neurons to Aß25-35 for 30 minutes, before adding Rg1 for 48 hours, with or without Akt or MAPK inhibitors, and assessed neuronal survival using Hoechst 33258 staining, and phosphorylation of ERK1/2 and Akt by western blot analysis. Rg1 induced neurite outgrowth, and this effect was blocked by API-2 (Akt inhibitor) and PD98059 (MAPK/ERK kinase inhibitor), but not by SP600125 or SB203580 (inhibitors of c-Jun N-terminal kinase and p38 MAPK, respectively). Consistent with this effect, Rg1 upregulated the phosphorylation of Akt and ERK1/2; these effects were reversed by API-2 and PD98059, respectively. In addition, Rg1 significantly reversed Aß25-35 -induced apoptosis; this effect was blocked by API-2 and PD98059, but not by SP600125 or SB203580. Finally, Rg1 significantly reversed the Aß25-35 -induced decrease in Akt and ERK1/2 phosphorylation, but API-2 prevented this reversal. Our results indicate that Rg1 enhances neurite outgrowth and protects against Aß25-35 -induced damage, and that its mechanism may involve the activation of Akt and ERK1/2 signaling.