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并且左旋多巴联合治疗通过激活 Nrf2 和抑制 NLRP3 信号通路来缓解大鼠帕金森病症状。

and levodopa combination alleviates Parkinson's disease symptoms in rats through activation of Nrf2 and inhibition of NLRP3 signaling pathways.

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

出版信息

Pharm Biol. 2023 Dec;61(1):1175-1185. doi: 10.1080/13880209.2023.2244176.

DOI:10.1080/13880209.2023.2244176
PMID:37559448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10416743/
Abstract

CONTEXT

Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson's disease (PD). Recently, we demonstrated that (D. Don) DC. [syn. D.Don, DC.] (Valerianaceae) (NJ) can alleviate PD.

OBJECTIVE

To explore the synergistic effect of NJ combined with levodopa against PD.

MATERIALS AND METHODS

The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways.

RESULTS

Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 ± 668.73 vs. 1501.41 ± 870.23,  < 0.01), enhanced the stay time on the rotating rod (84.86 ± 18.15 vs. 71.36 ± 17.53,  < 0.01) and the combination was superior to other treatments. The synergistic effects were related to NJ + levodopa (1.24 g/kg + 25 mg/kg) increasing the neurotransmitter levels by 38.80%-88.67% in PD rats, and inhibiting oxidative stress and NLRP3 pathway by activating Nrf2 pathway.

DISCUSSION AND CONCLUSIONS

NJ combined with levodopa is a promising therapeutic candidate for PD, which provides a scientific basis for the subsequent clinical combination therapy of levodopa to enhance the anti-PD effect.

摘要

背景

左旋多巴与中药联合应用对帕金森病(PD)有协同作用。最近,我们证明[syn. D.Don,DC.](缬草科)(NJ)可缓解 PD。

目的

探讨 NJ 与左旋多巴联合治疗 PD 的协同作用。

材料和方法

通过注射鱼藤酮建立 PD 模型。84 只 Sprague-Dawley 大鼠随机分为 7 组:假手术组、模型组、不同剂量 NJ(0.31、0.62 或 1.24g/kg)与左旋多巴(25mg/kg)联合组、左旋多巴单独(25 和 50mg/kg)组。通过药效学研究和核因子红细胞 2 相关因子 2(Nrf2)和富含 N 端含 Pyrin 结构域 3(NLRP3)途径的 NLR 家族蛋白表达检测,探讨联合用药的协同作用。

结果

与模型组相比,NJ+左旋多巴(1.24g/kg+25mg/kg)增加 PD 大鼠在旷场中的运动距离(2395.34±668.73 比 1501.41±870.23,<0.01),延长在旋转棒上的停留时间(84.86±18.15 比 71.36±17.53,<0.01),且联合用药优于其他治疗。协同作用与 NJ+左旋多巴(1.24g/kg+25mg/kg)增加 PD 大鼠神经递质水平(38.80%-88.67%)、通过激活 Nrf2 途径抑制氧化应激和 NLRP3 途径有关。

讨论与结论

NJ 与左旋多巴联合应用是 PD 的一种有前途的治疗候选药物,为随后的左旋多巴联合临床治疗增强抗 PD 作用提供了科学依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/5c02ca9bc51a/IPHB_A_2244176_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/fb5c32e5ad66/IPHB_A_2244176_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/615324614012/IPHB_A_2244176_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/e0bd654ba481/IPHB_A_2244176_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/ccaf4a9261df/IPHB_A_2244176_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/1abd6741f0df/IPHB_A_2244176_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/d1ae75cc4506/IPHB_A_2244176_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/dae37f254683/IPHB_A_2244176_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/c56617c289bc/IPHB_A_2244176_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/5c02ca9bc51a/IPHB_A_2244176_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/fb5c32e5ad66/IPHB_A_2244176_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/615324614012/IPHB_A_2244176_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/e0bd654ba481/IPHB_A_2244176_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/ccaf4a9261df/IPHB_A_2244176_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/1abd6741f0df/IPHB_A_2244176_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/d1ae75cc4506/IPHB_A_2244176_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/dae37f254683/IPHB_A_2244176_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/c56617c289bc/IPHB_A_2244176_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/10416743/5c02ca9bc51a/IPHB_A_2244176_F0009_C.jpg

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