Division of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52802, Republic of Korea.
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
Mol Neurobiol. 2019 Jan;56(1):39-55. doi: 10.1007/s12035-018-1020-1. Epub 2018 Apr 19.
Gintonin, a ginseng-derived glycolipoprotein isolated from ginseng, has been shown to be neuroprotective in several neurological disorders such as Alzheimer's disease models and depressive-like behaviors. In this study, we sought to investigate the potential protective mechanisms of gintonin in an in vivo MPTP and in vitro MPP-mediated Parkinson's disease (PD) model. We hypothesized that activation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1, potential therapeutic targets for neurodegeneration) with gintonin could abrogate PD-associated neurotoxicity by modulating the accumulation of α-synuclein, neuroinflammation, and apoptotic cell death in an MPTP/MPP models of PD. Our in vivo and in vitro findings suggest that the neuroprotective effects of gintonin were associated with the regulation of the Nrf2/HO-1 pathway, which regulated the expression of proinflammatory cytokines and nitric oxide synthase and apoptotic markers in the substantia nigra and striatum of the mice. Moreover, the neuroprotective effects of gintonin were also associated with a reduction in α-synuclein accumulation in the mouse substantia nigra and striatum. The neuroprotective effects of gintonin were further validated by analyzing the effects of gintonin on MPP-treated SH-SY5Y cells, which confirmed the protective effects of gintonin. It remains for future basic and clinical research to determine the potential use of gintonin in Parkinson's disease. However, to the best of our knowledge, marked alterations in biochemical and morphological setup of midbrain dopaminergic pathways by gintonin in MPTP mice model have not been previously reported. We believe that gintonin might be explored as an important therapeutic agent in the treatment of PD.
从人参中分离出的人参衍生糖脂蛋白——金藤素，已被证明在几种神经紊乱疾病中具有神经保护作用，如阿尔茨海默病模型和抑郁样行为。在这项研究中，我们试图研究金藤素在体内 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和体外 1-甲基-4-苯基吡啶离子（MPP）介导的帕金森病（PD）模型中的潜在保护机制。我们假设，通过激活核因子红细胞 2 相关因子 2/血红素加氧酶-1（Nrf2/HO-1，神经退行性变的潜在治疗靶点），金藤素可以通过调节α-突触核蛋白、神经炎症和凋亡细胞死亡来减轻 PD 相关的神经毒性在 PD 的 MPTP/MPP 模型中。我们的体内和体外研究结果表明，金藤素的神经保护作用与 Nrf2/HO-1 通路的调节有关，该通路调节了小鼠黑质和纹状体中促炎细胞因子和一氧化氮合酶以及凋亡标志物的表达。此外，金藤素还可以减少小鼠黑质和纹状体中α-突触核蛋白的积累，从而发挥神经保护作用。通过分析金藤素对 MPP 处理的 SH-SY5Y 细胞的影响，进一步验证了金藤素的神经保护作用，证实了金藤素的保护作用。未来的基础和临床研究需要确定金藤素在帕金森病中的潜在用途。然而，据我们所知，金藤素在 MPTP 小鼠模型中对中脑多巴胺能通路的生化和形态结构的显著改变以前尚未报道过。我们相信，金藤素可能被探索为治疗 PD 的重要治疗剂。
