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姜黄素在6-羟基多巴胺诱导的帕金森病大鼠模型中减轻运动症状的剂量。

The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model.

作者信息

Liu Xiaoyu, Zhang Hao, Li Chuanfen, Chen Zhibin, Gao Qian, Han Muxuan, Zhao Feng, Chen Dan, Chen Qiuyue, Hu Minghui, Li Zifa, Wei Sheng, Geng Xiwen

机构信息

Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China.

Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Heliyon. 2023 Jun 7;9(6):e16921. doi: 10.1016/j.heliyon.2023.e16921. eCollection 2023 Jun.

Abstract

BACKGROUND

Curcumin is a natural compound with extensive pharmacological effects. This research is to verify the optimal dose and administration duration efficacy of curcumin in alleviating the movement symptoms of Parkinson's disease (PD).

METHODS

Wistar rats were divided into six groups including control, model, levodopa treatment and low/middle/high (40/80/160 mg/kg/d) curcumin treatment groups. After stereotactic brain injection of 6-hydroxydopamine (6-OHDA), curcumin was given by intragastric administration for 2 weeks. To evaluate the drug effect, the rats received behavioral tests including apomorphine (APO)-induced rotation test, rotarod test and open field test. Then the rats were sacrificed and the brain slices including substantia nigra pars compacta (SNc) were used for immunofluorescence staining.

RESULTS

After 6-OHDA injection, the model group showed typical movement symptoms including the severe APO-induced rotation to the healthy side, decreased latency in the rotarod with constant or accelerative mode, and decreased total distance and average speed in the open field test. In the results of immunofluorescence staining, the 6-OHDA induced a severe damage of dopaminergic neurons in SNc. The 160 mg/kg/d treatment of curcumin to intervene for 2 weeks alleviated most of the behavioral disorders but the 40/80 mg/kg/d treatment showed limitations. Then, we compared the effect of 1 week intervention to the 2 weeks with 160 mg/kg/d treatment of curcumin to intervene and results indicated that the treatment of 2 weeks could better alleviate the symptoms.

CONCLUSIONS

Curcumin alleviated 6-OHDA-induced movement symptoms in a PD rat model. Additionally, the effect of curcumin against PD indicated dose and duration dependent and the intervention of 160 mg/kg/d for 2 weeks showed optimally therapeutic effect.

摘要

背景

姜黄素是一种具有广泛药理作用的天然化合物。本研究旨在验证姜黄素缓解帕金森病(PD)运动症状的最佳剂量和给药持续时间疗效。

方法

将Wistar大鼠分为六组,包括对照组、模型组、左旋多巴治疗组和低/中/高(40/80/160mg/kg/d)姜黄素治疗组。在立体定向脑内注射6-羟基多巴胺(6-OHDA)后,通过灌胃给予姜黄素2周。为评估药物效果,大鼠接受行为测试,包括阿扑吗啡(APO)诱导的旋转试验、转棒试验和旷场试验。然后处死大鼠,取包括黑质致密部(SNc)的脑片进行免疫荧光染色。

结果

注射6-OHDA后,模型组出现典型的运动症状,包括APO诱导的向健康侧严重旋转、转棒试验中恒定或加速模式下潜伏期缩短以及旷场试验中总距离和平均速度降低。在免疫荧光染色结果中,6-OHDA导致SNc中多巴胺能神经元严重损伤。160mg/kg/d的姜黄素治疗干预2周可缓解大部分行为障碍,但40/80mg/kg/d的治疗显示出局限性。然后,我们比较了160mg/kg/d的姜黄素治疗干预1周和2周的效果,结果表明2周治疗能更好地缓解症状。

结论

姜黄素可缓解PD大鼠模型中6-OHDA诱导的运动症状。此外,姜黄素对PD的作用呈剂量和时间依赖性,160mg/kg/d干预2周显示出最佳治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b75/10360947/a3b4ba2b3535/gr1.jpg

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