State Key Disciplines: Physiology (in incubation), Department of Physiology, Medical College of Qingdao University, Qingdao 266071, China.
Neuropharmacology. 2010 Feb;58(2):488-94. doi: 10.1016/j.neuropharm.2009.09.002. Epub 2009 Sep 8.
Ginsenoside-Rg1 is one of the pharmacologically active component isolated from ginseng. Our previous study observed the protective effect of Rg1 on iron accumulation in the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated Parkinson's disease (PD) mice. However, the mechanisms of this neuroprotective effect of Rg1 are unknown. In this study, we elucidated possible mechanisms for this effect using 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells. Previous study showed MPP+ treatment induced up-regulation of divalent metal transporter 1 without iron responsive element (DMT1-IRE) in MES23.5 cells. In the present study, we observed that pretreatment with Rg1 could inhibit MPP+-induced up-regulation of DMT1-IRE in MES23.5 cells. Up-regulation of DMT1-IRE by MPP+ treatment was associated with ROS production and translocation of nuclear factor-kappaB (NF-kappaB) to nuclei, both of which were significantly inhibited by Rg1 pretreatment. The role of ROS and NF-kappaB in the up-regulation of DMT1-IRE was supported by application of an antioxidant NAC and BAY 11-7082, an inhibitor of IkappaBalpha phosphorylation. Furthermore, we also showed Rg1 could decrease DMT1-mediated ferrous iron uptake and iron-induced cell damage by inhibiting the up-regulation of DMT1-IRE. These results indicate that Rg1 protected the MPP+-treated MES23.5 cells via attenuating DMT1-IRE up-regulation likely through inhibition of ROS-NF-kappaB pathway; Attenuation of DMT1-IRE expression decreased the iron influx and iron-induced oxidative stress.
人参皂苷 Rg1 是从人参中分离得到的具有药理活性的成分之一。我们之前的研究观察到 Rg1 对 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的帕金森病（PD）小鼠黑质（SN）中铁积累的保护作用。然而，Rg1 的这种神经保护作用的机制尚不清楚。在这项研究中，我们使用 1-甲基-4-苯基吡啶鎓（MPP(+））处理的 MES23.5 细胞阐明了这种作用的可能机制。先前的研究表明，MPP+处理诱导二价金属转运蛋白 1（DMT1-IRE）在 MES23.5 细胞中的上调，而没有铁反应元件（IRE）。在本研究中，我们观察到 Rg1 预处理可以抑制 MPP+诱导的 DMT1-IRE 在 MES23.5 细胞中的上调。MPP+处理引起的 DMT1-IRE 上调与 ROS 产生和核因子-κB（NF-κB）核转位有关，Rg1 预处理显著抑制了这两种作用。ROS 和 NF-κB 在 DMT1-IRE 上调中的作用得到了抗氧化剂 NAC 和 IkappaBalpha 磷酸化抑制剂 BAY 11-7082 的应用支持。此外，我们还表明，Rg1 可以通过抑制 DMT1-IRE 的上调来减少 DMT1 介导的亚铁摄取和铁诱导的细胞损伤。这些结果表明，Rg1 通过抑制 ROS-NF-κB 通路减弱 DMT1-IRE 的上调来保护 MPP+处理的 MES23.5 细胞；减弱 DMT1-IRE 表达可减少铁内流和铁诱导的氧化应激。
