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天麻通过使帕金森病 6-OHDA 损伤模型中 FosB 和 ERK 的激活正常化来缓解 L-DOPA 诱导的运动障碍。

Gastrodia elata Blume alleviates L-DOPA-induced dyskinesia by normalizing FosB and ERK activation in a 6-OHDA-lesioned Parkinson's disease mouse model.

机构信息

Studies of Translational Acupuncture Research (STAR), Acupuncture & Meridian Science Research Center (AMSRC), Kyung Hee University, 1 Hoegi-dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.

出版信息

BMC Complement Altern Med. 2014 Mar 20;14:107. doi: 10.1186/1472-6882-14-107.

Abstract

BACKGROUND

Gastrodia elata Blume (GEB), commonly used medicinal herb, has been reported as a promising candidate for neurodegenerative diseases such as Parkinson's disease. The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), is the gold-standard drug for Parkinson's disease, but long-term treatment results in the L-dopa-induced dyskinesia (LID). This study was undertaken to examine the beneficial effects of GEB on L-DOPA induced dyskinesia in 6-hydroxydopamine (6-OHDA)-induced experimental Parkinsonism.

METHODS

We tested the effects of GEB on LID in 6-hydroxydopamine hydrochloride-hemiparkinsonian mice. To analyze the dyskinetic anomalies, we measured abnormal involuntary movement (AIM). Immunohistological analyses of pERK and FosB expressions in the striatum are performed to explore the mechanism of GEB on LID.

RESULTS

The finding of this study demonstrated that GEB (200, 400 and 800 mg/kg) alleviated L-dopa induced AIMs in a dose-dependent manner. In each integrative AIM subtype analysis, we also found that the GEB (400 and 800 mg/kg) treatment decreased L-DOPA-induced axial, limb, orolingual, and locomotive AIMs compared to the LID group. In addition, GEB normalized the abnormal LID-induced increase of pERK1/2 and FosB, the immediate early genes of LID in the striatum.

CONCLUSIONS

In conclusion, our results provide a novel insight into the pharmacological actions of GEB that could have a benefit for PD patients through the reduction of LID.

摘要

背景

天麻(GEB)是一种常用的药用植物,已被报道为治疗帕金森病等神经退行性疾病的有前途的候选药物。多巴胺前体 L-3,4-二羟基苯丙氨酸(L-DOPA)是治疗帕金森病的金标准药物,但长期治疗会导致 L-多巴诱导的运动障碍(LID)。本研究旨在探讨 GEB 对 6-羟多巴胺(6-OHDA)诱导的实验性帕金森病中 L-DOPA 诱导运动障碍的有益作用。

方法

我们测试了 GEB 对 6-羟多巴胺盐酸盐半帕金森病小鼠 LID 的影响。为了分析运动障碍异常,我们测量了异常不自主运动(AIM)。通过免疫组织化学分析纹状体中 pERK 和 FosB 的表达,探讨 GEB 对 LID 的作用机制。

结果

本研究发现,GEB(200、400 和 800mg/kg)以剂量依赖的方式减轻 L-多巴诱导的 AIMs。在每种综合 AIM 亚型分析中,我们还发现 GEB(400 和 800mg/kg)治疗可降低 L-DOPA 诱导的轴向、肢体、口颊和运动性 AIMs,与 LID 组相比。此外,GEB 使 LID 诱导的 pERK1/2 和 FosB 异常增加正常化,纹状体中 LID 的即刻早期基因。

结论

总之,我们的结果提供了 GEB 药理作用的新见解,通过减少 LID,可能对帕金森病患者有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/3994477/8a9ef87aa8c2/1472-6882-14-107-1.jpg

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