Wu Jiaying, Yang Hongyu, Zhao Qingwei, Zhang Xingguo, Lou Yijia
Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Division of Cardio-Cerebral Vascular and Hepatic Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
Int J Mol Med. 2016 Mar;37(3):781-8. doi: 10.3892/ijmm.2016.2485. Epub 2016 Feb 8.
Ginsenoside Rg1 (Rg1) is a multipotent triterpene saponin extracted from ginseng, and has been proven to act as a nootropic agent against various types of neurological damage. The present study was designed to investigate the neuroprotective effect and the underlying mechanisms of Rg1 on apoptosis induced by β-amyloid peptide 25-35 (Aβ25-35) in primary cultured cortical neurons. The primary neurons were preincubated with 20 µM Rg1 for 24 h and exposed to 10 µM Aβ25-35 for 72 h. In the present study, we found that Rg1 prevented nuclear factor κ-light-chain‑enhancer of activated B cells (NF-κB) nuclear translocation and IκB-α phosphorylation in primary cultured cortical neurons after Aβ25-35 exposure by scavenging excess reactive oxygen species (ROS); ROS was measured using DCFDA and examined using a fluorescence microscope. In addition, Rg1 successfully suppressed Aβ25‑35-inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in a NF-κB-dependent manner; the suppression of NO was clearly illustrated by the NO production assay. Pretreatment of the cells with Rg1 elevated the proportion of Bcl-2/Bax, lessened the release of cytochrome c from mitochondria into cytoplasm and then blocked mitochondrial apoptotic cascades after Aβ25-35 insult by lowering NO generation. Taken together, our data demonstrate that Rg1 rescues primary cultured cortical neurons from Aβ25-35-induced cell apoptosis through the downregulation of the NF-κB/NO signaling pathway.
人参皂苷Rg1（Rg1）是从人参中提取的一种具有多种功能的三萜皂苷，已被证明可作为一种益智剂，对抗各种类型的神经损伤。本研究旨在探讨Rg1对原代培养皮层神经元中β-淀粉样肽25-35（Aβ25-35）诱导的细胞凋亡的神经保护作用及其潜在机制。原代神经元先用20μM Rg1预孵育24小时，然后暴露于10μM Aβ25-35中72小时。在本研究中，我们发现Rg1通过清除过量的活性氧（ROS），防止Aβ25-35暴露后原代培养皮层神经元中核因子κB轻链增强子（NF-κB）的核转位和IκB-α磷酸化；ROS使用DCFDA进行测量，并通过荧光显微镜进行检测。此外，Rg1以NF-κB依赖的方式成功抑制了Aβ25-35诱导的一氧化氮合酶（iNOS）表达和一氧化氮（NO）生成；NO生成测定清楚地说明了对NO的抑制作用。用Rg1预处理细胞可提高Bcl-2/Bax的比例，减少细胞色素c从线粒体释放到细胞质中，然后通过降低NO生成，在Aβ25-35损伤后阻断线粒体凋亡级联反应。综上所述，我们的数据表明，Rg1通过下调NF-κB/NO信号通路，使原代培养皮层神经元免受Aβ25-35诱导的细胞凋亡。
