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Proliferation and committed differentiation into dopamine neurons of neural stem cells induced by the active ingredients of radix astragali

机译:黄芪有效成分诱导神经干细胞向多巴胺神经元的增殖和定向分化

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摘要

Neural stem cells (NSCs) are important cellular sources of transplantation therapies for Parkinson’s disease. This study aimed to determine the effects of extracts of radix astragali on the proliferation and differentiation into dopamine (DA) neurons in NSCs. NSCs were dealt with astragaloside IV (ASI), astragalus polysaccharide (APS), and astraisoflavan (ASF), the main active ingredients of radix astragali. First, the results from cell-count kit-8 (CCK-8) assay showed that ASI, ASF, and APS had positive effects on the proliferation of NSCs. Next, we also confirmed the effects of ASI, APS, and ASF on BrdU and nestin by immunocytochemistry. Moreover, results from quantitative RT-PCR showed ASI, APS, and ASF could promote the expressions of tyrosine hydroxylase and dopamine transporter mRNA, which are specifically expressed in DA neurons. Simultaneously, sonic hedgehog (Shh), orphan nuclear hormone 1 (Nurr1), and pituitary homeobox 3 (Ptx3) are considered to motivate the formation of DA neurons. Our result showed ASI, APS, and ASF can also promote the expressions of Shh, Nurr1, and Ptx3 mRNAs. In conclusion, our study verifies that the active ingredients of radix astragali can promote the proliferation of NSCs and induce NSC differentiation toward DA neurons in vitro. These phenomena may occur through upregulation of Shh, Nurr1, and Ptx3 in the process of drug treatment.
机译:神经干细胞(NSC)是帕金森氏病移植治疗的重要细胞来源。这项研究旨在确定黄芪提取物对NSC中神经元增殖和分化为多巴胺(DA)神经元的影响。 NSCs处理了黄芪甲苷(ASI),黄芪多糖(APS)和黄芪黄酮(ASF),这是黄芪的主要活性成分。首先,细胞计数试剂盒8(CCK-8)分析的结果表明,ASI,ASF和APS对NSC的增殖具有积极作用。接下来,我们还通过免疫细胞化学证实了ASI,APS和ASF对BrdU和nestin的影响。此外,定量RT-PCR的结果表明,ASI,APS和ASF可以促进酪氨酸羟化酶和多巴胺转运蛋白mRNA的表达,它们在DA神经元中特异性表达。同时,声音刺猬(Shh),孤儿核激素1(Nurr1)和垂体同源盒3(Ptx3)被认为可以促进DA神经元的形成。我们的结果表明,ASI,APS和ASF也可以促进Shh,Nurr1和Ptx3 mRNA的表达。总之,我们的研究验证了黄芪的有效成分可以促进NSC的增殖并诱导NSC向DA神经元分化。这些现象可能是通过在药物治疗过程中Shh,Nurr1和Ptx3的上调而发生的。

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