β-Asarone Inhibits IRE1/XBP1 Endoplasmic Reticulum Stress Pathway in 6-OHDA-Induced Parkinsonian Rats
β-Asarone Inhibits IRE1/XBP1 Endoplasmic Reticulum Stress Pathway in 6-OHDA-Induced Parkinsonian Rats
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DOI：
10.1007/s11064-016-1922-0
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发表时间：
2016-08-01
影响因子：
4.4
通讯作者：
Fang, Yongqi
中科院分区：
文献类型：
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作者：
Ning, Baile;Deng, Minzhen;Fang, Yongqi
帕金森病（Parkinson's disease，PD）是一种神经退行性疾病，遗传和环境因素共同作用于PD的发病。对本病病理认识的局限性制约了临床治疗方法的改进。近年来的研究表明，内质网应激在帕金森病的发病机制中起重要作用。有一个神经保护作用，部分通过调节ER应激介导。β-细辛醚是石菖蒲挥发油的主要成分。我们的团队观察到β-细辛醚可以改善帕金森病大鼠的行为;增加HVA，Dopacl和5-HIAA水平;并降低α-突触核蛋白水平。我们推测β-细辛醚对帕金森病大鼠的保护作用可能是通过内质网应激途径实现的。为了证明这一假设，我们研究了β-细辛脑治疗后6-羟基多巴胺（6-OHDA）诱导的帕金森病大鼠的葡萄糖调节蛋白78（GRP 78）和C/EBP同源结合蛋白（CHOP）的mRNA水平。此外，还研究了肌醇需要酶1/X-Box结合蛋白1（IRE 1/XBP 1）ER应激途径。结果表明，β-细辛醚可抑制GRP 78和CHOP的mRNA水平，并伴有磷酸化IER 1（p-IRE 1）和XBP 1的表达下降。我们推测β-细辛醚可能通过IRE 1/XBP 1通路对6-OHDA诱导的帕金森病大鼠具有保护作用。综上所述，β-细辛醚可能成为治疗帕金森病的潜在药物。
Parkinson's disease (PD) is a neurodegenerative disease, with genetics and environment contributing to the disease onset. The limited pathological cognize of the disease restrained the approaches to improve the clinical treatment. Recently, studies showed that endoplasmic reticulum (ER) stress played an important role in the pathogenesis of PD. There was a neuroprotective effect partly mediated by modulating ER stress. beta-Asarone is the essential constituent of Acorus tatarinowii Schott volatile oil. Our team observed that beta-asarone could improve the behavior of parkinsonian rats; increase the HVA, Dopacl, and 5-HIAA levels; and reduce alpha-synuclein levels. Here we assumed that the protective role of beta-asarone on parkinsonian rats was mediated via ER stress pathway. To prove the hypothesis we investigated the mRNA levels of glucose regulated protein 78 (GRP78) and C/EBP homologous binding protein (CHOP) in 6-hydroxy dopamine (6-OHDA) induced parkinsonian rats after beta-asarone treatment. Furthermore, the inositol-requiring enzyme 1/X-Box Binding Protein 1 (IRE1/XBP1) ER stress pathway was also studied. The results showed that beta-asarone inhibited the mRNA levels of GRP78 and CHOP, accompanied with the delined expressions of phosphorylated IER1 (p-IRE1) and XBP1. We deduced that beta-asarone might have a protective effect on the 6-OHDA induced parkinsonian rats via IRE1/XBP1 Pathway. Collectively, all data indicated that beta-asarone might be a potential candidate of medicine for clinical therapy of PD.