The Central Laboratory, Changchun Normal University, Changchun, Jilin, PR China.
The Central Laboratory, Changchun Normal University, Changchun, Jilin, PR China.
Neuropharmacology. 2017 Apr;116:412-420. doi: 10.1016/j.neuropharm.2017.01.009. Epub 2017 Jan 16.
Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP-induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD). Our results demonstrated that PF treatment ameliorated the behavioral deficits of "in spontaneous motor activity and latency to fall of the rotarod test", and reduced dopaminergic cell loss that were induced by MPTP in a dose-dependent manner in an in vivo model of PD. In addition, we found that treatment of PF protected dopaminergic neurons by preventing MPTP-induced decreases in striatal and substantia nigra dopaminergic transporter (DAT) and tyrosine hydroxylase (TH) protein levels, and by changing dopamine catabolism and inhibiting dopamine turnover. Furthermore, it was also associated with up-regulation of the Bcl-2/BAD ratio, and inhibition of the activation of caspase-9 and caspase-3. These results showed that PF promoted dopamine neuron survival in vivo due to the MAO-B inhibition, and the PI3K/Akt signaling pathway may have mediated the protection of PF against MPTP, suggesting that PF treatment might represent a neuroprotective treatment for PD.
芍药苷（PF）是白芍根中的一种主要生物活性成分，具有低毒性，并已被证明具有神经保护作用。我们的体外实验表明，PF 通过 Bcl-2/Bax/caspase-3 途径对 MPP 诱导的 PC12 细胞损伤和凋亡具有显著的神经保护作用。本研究的目的是探讨 PF 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。我们的结果表明，PF 治疗改善了“自发运动活动和旋转棒试验中跌倒潜伏期”的行为缺陷，并以剂量依赖的方式减轻了 MPTP 诱导的 PD 体内模型中多巴胺能细胞的丢失。此外，我们发现 PF 通过防止 MPTP 诱导的纹状体和黑质多巴胺转运蛋白（DAT）和酪氨酸羟化酶（TH）蛋白水平的降低，改变多巴胺的代谢并抑制多巴胺的转化，从而保护多巴胺能神经元。此外，它还与 Bcl-2/BAD 比值的上调以及 caspase-9 和 caspase-3 激活的抑制有关。这些结果表明，PF 通过 MAO-B 抑制促进多巴胺神经元在体内存活，而 PI3K/Akt 信号通路可能介导了 PF 对 MPTP 的保护作用，提示 PF 治疗可能是 PD 的一种神经保护治疗方法。
