Hu Ming, Li Fangming, Wang Weidong
Department of Neurology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
Drug Des Devel Ther. 2018 Mar 16;12:565-573. doi: 10.2147/DDDT.S156920. eCollection 2018.
Parkinson's disease (PD) is a progressive neurodegenerative disease which is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc).
In this study, the neuroprotective effect of vitexin (Vit), a flavonoid compound isolated from was examined in PD models both in vitro and in vivo.
On SH-SY5Y cells, methyl-4-phenylpyridine (MPP) treatment suppressed cell viability, induced apoptosis, and increased Bax/Bcl-2 ratio and caspase-3 activity. However, Vit improved these parameters induced by MPP treatment significantly. Further study disclosed that Vit enhanced the phosphorylation of PI3K and Akt which was downregulated by MPP in SH-SY5Y cells, the effect of which could be blocked by PI3K inhibitor LY294002 and activated by PI3K activator IGF-1. Moreover, results from the pole test and traction test suggested that Vit pretreatment prevented bradykinesia and alleviated the initial lesions caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in MPTP-treated mouse PD model. Vit also enhanced the activation of PI3K and Akt and suppressed the ratio of Bax/Bcl-2 and caspase-3 activity in MPTP-treated mice.
Taken together, this study demonstrated that Vit protected dopaminergic neurons against MPP/MPTP-induced neurotoxicity through the activation of PI3K/Akt signaling pathway. Our findings may facilitate the clinical application of Vit in the therapy of PD.
帕金森病（PD）是一种进行性神经退行性疾病，其特征是黑质致密部（SNpc）中的多巴胺能神经元变性。
在本研究中，对从[植物名称未给出]中分离出的黄酮类化合物牡荆素（Vit）在体外和体内PD模型中的神经保护作用进行了研究。
在SH-SY5Y细胞上，甲基-4-苯基吡啶（MPP）处理抑制细胞活力，诱导细胞凋亡，并增加Bax/Bcl-2比值和半胱天冬酶-3活性。然而，Vit显著改善了MPP处理诱导的这些参数。进一步研究发现，Vit增强了PI3K和Akt的磷酸化，而MPP在SH-SY5Y细胞中使其下调，PI3K抑制剂LY294002可阻断其作用，PI3K激活剂IGF-1可激活其作用。此外，杆试验和牵引试验结果表明，Vit预处理可预防1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的小鼠PD模型中的运动迟缓，并减轻由MPTP引起的初始损伤。Vit还增强了MPTP处理小鼠中PI3K和Akt的激活，并抑制了Bax/Bcl-2比值和半胱天冬酶-3活性。
综上所述，本研究表明Vit通过激活PI3K/Akt信号通路保护多巴胺能神经元免受MPP/MPTP诱导的神经毒性。我们的发现可能有助于Vit在PD治疗中的临床应用。
