The neuroprotective effect of modified Yeoldahanso-tang via autophagy enhancement in models of Parkinson's disease
The neuroprotective effect of modified Yeoldahanso-tang via autophagy enhancement in models of Parkinson's disease
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DOI：
10.1016/j.jep.2010.12.016
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发表时间：
2011-03-24
影响因子：
5.4
通讯作者：
Yang, Hyun Ok
中科院分区：
文献类型：
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作者：
Bae, Nayoung;Ahn, Taekwon;Yang, Hyun Ok
研究目的：改良Yeoldahanso-tang（MYH）是一种韩国草药配方，含有10种草药：葛根（Willd.）噢，当归，黄芩，桔梗，升麻，白萝卜，远志，石菖蒲和龙眼（Dimoccupus longan Lour.）10味药材的干重组成比为6：4：2：1：2：2：2：4：6：6。MYH在韩国已被用于治疗健忘症、脑功能减退症和痴呆症。本研究旨在探讨MYH用于帕金森病（PD）预防和治疗的可能性。具体来说，我们做了努力，以证明MYH的神经保护作用，使用类似的实验方法，在最近的研究PD.Materials和方法：1-甲基-4-苯基吡啶（MPP+）（400 μ M）被用来诱导细胞毒性在NGF（神经生长因子）分化的PC 12细胞。使用μ测定法测量细胞活力。MYH在NGF分化的PC 12细胞中诱导的自噬使用LC 3和beclin 1抗体的免疫印迹测定来测量。使用蛋白酶体抑制剂lactacystin（10 μ M）在NGF分化的PC 12细胞中引起UPS功能障碍。使用免疫印迹试验用泛素抗体测量MYH对聚集蛋白的清除。1-甲基-4-苯基-1，2，3，6-四氢苯基吡啶（MPTP）（20 mg/kg，4次i. p.）引起C57 BL/6小鼠黑质损伤。结果：MYH对MPP+诱导的NGF分化的PC 12细胞损伤具有保护作用。MYH对乳胱氨酸诱导的NGF分化的PC 12细胞死亡提供神经保护，其作用部分是通过增强聚集蛋白的降解而增强自噬介导的。此外，在C57 BL/6小鼠模型与MFTP诱导的黑质损伤，MYH抑制黑质部（SNPC）和TH-IR纤维的光密度在纹状体（ST）的减少TH-阳性神经元的损失。结论：我们所有的研究结果表明，MYH治疗具有神经保护作用，部分介导的自噬增强。MYH可能是一个很有前途的草药配方，用于预防和治疗神经退行性疾病，特别是PD。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Aim of study: Modified Yeoldahanso-tang (MYH) is a Korean herbal formula, containing 10 herbs: Pueraria lobata (Willd.) Ohwi. Angelica tenuissima Nakai, Scutellaria baicalensis Georgi, Platycodon grandiflorum (Jacq), Angelicae Dahurica, Cimicifuga heracleifolia Kom, Raphanus sativa L, Polygala tenuifolia (Willd.), Acorus gramineus Soland. and Dimoccupus longan Lour. The constitutive ratio of the ten herbs is at 6:4:2:1:2:2:2:4:6:6 in dry weight. MYH has been used to treat amnesia, hypochondria and dementia in Korea. In this study, we explored the possibility of using MYH in the prevention and treatment of Parkinson's disease (PD). Specifically, we made an effort to demonstrate the neuroprotective effects of MYH using experimental methods similar to those used in a recent study of PD.Materials and methods: 1-Methyl-4-phenylpyridinium (MPP+) (400 p,M) was used to induce cytotoxicity in NGF (nerve growth factor)-differentiated PC12 cells. Cell viability was measured using a mu assay. Induction of autophagy by MYH in NGF-differentiated PC12 cells was measured using an immunoblotting assay with LC3 and beclin 1 antibodies. The proteasomal inhibitor lactacystin (10 p,M) was used to cause UPS dysfunction in NGF-differentiated PC12 cells. Clearance of aggregated proteins by MYH was measured using an immunoblotting assay with an ubiquitin antibody. 1-Methyl-4-phenyl-1,2,3,6-tetrahydrophenylpyridine (MPTP) (20 mg/kg, 4 times i.p.) caused substantia nigra injuries in C57BL/6 mice. Dopamine (DA) neurons were identified using a tyrosine hydroxylase-immunohistochemistry (TH-IHC) assay with a rabbit anti-TH antibody.Results: Our findings indicate that MYH provides protection against MPP+-induced injury in NGF-differentiated PC12 cell. And MYH provides neuroprotection against lactacystin-induced NGF-differentiated PC12 cell death, which effect is partially mediated by autophagy enhancement through enhanced degradation of aggregated proteins. Additionally, in a C57BL/6 mice model with MFTP-induced substantia nigra injuries, MYH inhibits both the loss of TH-positive neurons in the substantia nigra pars compacta (SNpc) and the reduction of the optical density of TH-IR fibers in the striatum (ST).Conclusions: All of our results indicate that MYH treatment has neuroprotective effects that are partially mediated by autophagy enhancement. MYH may be a promising herbal formula for the prevention and treatment of neurodegenerative diseases, especially PD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.