Cimifugin Improves Motor Function Through Suppression of the NLRP3 Inflammasome in an Animal Model of Parkinson's Disease

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Natural Product Communications Pub Date : 2024-09-10 DOI:10.1177/1934578x241265938

Ji Yun Lee, Min Jae Kim, Byung Tae Choi, Young Ju Yun, Seo-Yeon Lee, Hwa Kyoung Shin

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引用次数: 0

Abstract

Objective: Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons and persistent neuroinflammation in the substantia nigra (SN), triggering a dopamine deficiency that can lead to movement disorders. Neuroinflammation is a common feature of aging brains and neurodegenerative diseases. Inflammasome-related neuroinflammation is involved in the progression of PD. Methods: The effects of cimifugin was investigated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Cimifugin is one of the main components of Saposhnikovia divaricata (Turcz.) Schischkin. Behavioral tests, such as the rotarod, pole, and traction tests, were conducted to measure the recovery effects of Parkinson-related motor deficiencies. Results: Our analyses showed that cimifugin treatment mitigates motor dysfunction in a dose-dependent manner. In addition, cimifugin conferred neuroprotection by increasing the survival of dopaminergic neurons, as measured by tyrosine hydroxylase immunostaining. Neuroinflammation was reduced by cimifugin by inhibiting NLR family pyrin domain-containing 3 (NLRP3)/caspase-1/interleukin 1β signaling in the MPTP-insulted SN. Moreover, monosodium urate crystals, an NLRP3 agonist, reversed cimifugin-induced improvement in motor function in the PD model. Conclusion: These results suggest that cimifugin administration is a potential therapeutic strategy for mitigating PD.

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Cimifugin 通过抑制帕金森病动物模型中的 NLRP3 炎症体改善运动功能

目的：帕金森病（Parkinson's disease）是一种神经退行性疾病：帕金森病（Parkinson's disease，PD）是一种神经退行性疾病，其特征是黑质（SN）中多巴胺能神经元的丧失和持续的神经炎症，引发多巴胺缺乏，从而导致运动障碍。神经炎症是大脑衰老和神经退行性疾病的共同特征。与炎症体相关的神经炎症与帕金森病的进展有关。研究方法在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病小鼠模型中研究了cimifugin的作用。Cimifugin 是 Saposhnikovia divaricata (Turcz.) Schischkin 的主要成分之一。为了测量帕金森氏症相关运动缺陷的恢复效果，对小鼠进行了行为测试，如转体测试、杆测试和牵引测试。结果显示我们的分析表明，cimifugin能以剂量依赖的方式缓解运动功能障碍。此外，通过酪氨酸羟化酶免疫染色法测定，cimifugin 还能提高多巴胺能神经元的存活率，从而起到神经保护作用。cimifugin通过抑制MPTP侵袭的SN中的NLR家族含吡咯啉结构域3（NLRP3）/caspase-1/白细胞介素1β信号传导，减轻了神经炎症。此外，NLRP3激动剂尿酸单钠盐晶体逆转了cimifugin诱导的帕金森病模型运动功能改善。结论这些结果表明，服用cimifugin是缓解帕金森病的一种潜在治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Natural Product Communications 工程技术-食品科技

CiteScore

3.10

自引率

11.10%

发文量

254

审稿时长

2.7 months

期刊介绍： Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products. Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products. Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products.