Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai R&D Center for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Münster, Germany.
Toxicology. 2019 Oct 1;426:152256. doi: 10.1016/j.tox.2019.152256. Epub 2019 Aug 2.
Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Accumulating evidences implicate the beneficial role of estrogen in the therapy of PD.
In the present study, the protective function of luteolin-7-O-glucoside (LUT-7G), a natural flavonoid, was investigated in 1-methyl-4-phenylpyridinium (MPP) treated SH-SY5Y cells and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mice.
Pre-treatment of LUT-7G increased the viability and reduced the apoptosis of SH-SY5Y cells treated by MPP. At molecular level, the Bcl-2/Bax ratio was increased, while the expression of cleaved caspase 3 was markedly lessened. Moreover, LUT-7G increased the expression of estrogen receptor (ER), ERα and ERβ, and enhanced the activation of ERK1/2/STAT3/c-Fos that could be abolished by ER antagonists. Furthermore, in vivo experiment indicated that pre-treatment of LUT-7G improved the bradykinesia, and enhanced the muscle strength as well as the balancing capacity of mice treated with MPTP. And LUT-7G prevented the injury of TH positive cells in substantia nigra and increased TH positive nerve fibers in striatum. In addition, pre-treatment of LUT-7G also significantly diminished the MPTP-induced gliosis in substantia nigra.
LUT-7G effectively protected dopaminergic neurons against MPP or MPTP-induced toxicity, probably by activating the ER-mediated signaling pathway. Our findings explore the therapeutic potential of LUT-7G for PD therapy.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质（SN）中多巴胺能神经元的退化。越来越多的证据表明，雌激素在 PD 的治疗中具有有益作用。
在本研究中，研究了天然黄酮类化合物芦丁-7-O-葡萄糖苷（LUT-7G）对 1-甲基-4-苯基吡啶（MPP）处理的 SH-SY5Y 细胞和 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的小鼠的保护作用。
LUT-7G 预处理可增加 MPP 处理的 SH-SY5Y 细胞的活力并减少细胞凋亡。在分子水平上，Bcl-2/Bax 比值增加，而 cleaved caspase 3 的表达明显减少。此外，LUT-7G 增加了雌激素受体（ER）、ERα和 ERβ的表达，并增强了 ERK1/2/STAT3/c-Fos 的激活，而 ER 拮抗剂可消除这种激活。此外，体内实验表明，LUT-7G 预处理可改善 MPTP 处理小鼠的运动迟缓，并增强肌肉力量和平衡能力。LUT-7G 可防止 TH 阳性细胞在黑质中的损伤，并增加纹状体中 TH 阳性神经纤维。此外，LUT-7G 预处理还可显著减轻 MPTP 诱导的黑质中神经胶质细胞的增生。
LUT-7G 可有效保护多巴胺能神经元免受 MPP 或 MPTP 诱导的毒性，这可能是通过激活 ER 介导的信号通路实现的。我们的研究结果探索了 LUT-7G 治疗 PD 的治疗潜力。
