Department of Scientific Research, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
Toxicol Lett. 2013 Oct 24;222(2):155-63. doi: 10.1016/j.toxlet.2013.07.020. Epub 2013 Aug 1.
Our in vitro experiments suggested that tetrahydroxystilbene glucoside (TSG) affords a significant neuroprotective effect against MPP⁺-induced damage and apoptosis in PC12 cells though activation of the PI3K/Akt pathway. This study was aimed to investigate the potential neuroprotective effect of TSG in 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-treated mouse model of Parkinson's disease (PD). We found that treatment of TSG protected dopaminergic neurons by preventing MPTP-induced decreases in substantia nigra tyrosine hydroxylase (TH)-positive cells and striatal dopaminergic transporter (DAT) protein levels. Furthermore, it was also associated with increasing striatal Akt and GSK3β phosphorylation, up-regulation of the Bcl-2/BAD ratio, and inhibition of the activation of caspase-9 and caspase-3. These results showed that TSG promoted dopamine neuron survival in vivo, the PI3K/Akt signaling pathway may have mediated the protection of TSG against MPTP, suggesting that TSG treatment might represent a neuroprotective treatment for PD.
我们的体外实验表明，四羟基二苯乙烯葡萄糖苷（TSG）通过激活 PI3K/Akt 通路，对 MPP⁺诱导的 PC12 细胞损伤和凋亡提供显著的神经保护作用。本研究旨在探讨 TSG 在 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病（PD）小鼠模型中的潜在神经保护作用。我们发现，TSG 通过防止 MPTP 诱导的黑质酪氨酸羟化酶（TH）阳性细胞和纹状体多巴胺转运蛋白（DAT）蛋白水平下降，来保护多巴胺能神经元。此外，它还与增加纹状体 Akt 和 GSK3β磷酸化、上调 Bcl-2/BAD 比值以及抑制 caspase-9 和 caspase-3 的激活有关。这些结果表明，TSG 促进了体内多巴胺神经元的存活，PI3K/Akt 信号通路可能介导了 TSG 对 MPTP 的保护作用，提示 TSG 治疗可能代表 PD 的一种神经保护治疗方法。
