Ginsenoside Rg1 exerts neuroprotective effects in 3-nitropronpionic acid-induced mouse model of Huntington's disease via suppressing MAPKs and NF-κB pathways in the striatum
Ginsenoside Rg1 exerts neuroprotective effects in 3-nitropronpionic acid-induced mouse model of Huntington's disease via suppressing MAPKs and NF-κB pathways in the striatum
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人参皂苷 Rg1 通过抑制纹状体中的 MAPK 和 NF-κB 通路，在 3-硝基丙酸诱导的亨廷顿病小鼠模型中发挥神经保护作用
DOI：
10.1038/s41401-020-00558-4
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发表时间：
2020-11-19
影响因子：
8.2
通讯作者：
Chen, Nai-hong
中科院分区：
文献类型：
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作者：
Yang, Xiong;Chu, Shi-feng;Chen, Nai-hong
亨廷顿病(HD)是一种主要的神经退行性疾病，以纹状体萎缩、不自主运动和运动协调障碍为特征。人参皂苷Rg1是人参中的有效成分，具有多种神经保护作用，毒副作用小。在这项研究中，我们研究了Rg1对HD小鼠模型的潜在治疗作用，并探讨了其潜在的机制。采用3-硝基丙酸(3-NP，I.P.)诱导小鼠HD模型。四天。从注射3-NP的第一天起，给予Rg1(10、20、40 mg中心点kg(-1)，P.O.)。为期5天。我们发现，口服Rg1可以减轻3-NP诱导的体重减轻和行为缺陷。此外，Rg1可改善3-NP所致的纹状体神经元丢失和超微结构损伤。此外，Rg1可减少3-NP诱导的细胞凋亡，并抑制纹状体内炎症介质小胶质细胞的激活。我们发现Rg1通过抑制3-NP诱导的纹状体MAPKs和NF-kappaβ信号通路的激活而发挥神经保护作用。因此，我们的结果提示，Rg1通过抑制MAPKs和NF-kappaβ信号通路对3-NP诱导的HD小鼠模型起到治疗作用。Rg1可作为HD的一种新的治疗选择。
Huntington's disease (HD) is one of main neurodegenerative diseases, characterized by striatal atrophy, involuntary movements, and motor incoordination. Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, possesses a variety of neuroprotective effects with low toxicity and side effects. In this study, we investigated the potential therapeutic effects of Rg1 in a mouse model of HD and explored the underlying mechanisms. HD was induced in mice by injection of 3-nitropropionic acid (3-NP, i.p.) for 4 days. From the first day of 3-NP injection, the mice were administered Rg1 (10, 20, 40 mg center dot kg(-1), p.o.) for 5 days. We showed that oral pretreatment with Rg1 alleviated 3-NP-induced body weight loss and behavioral defects. Furthermore, pretreatment with Rg1 ameliorated 3-NP-induced neuronal loss and ultrastructural morphological damage in the striatum. Moreover, pretreatment with Rg1 reduced 3-NP-induced apoptosis and inhibited the activation of microglia, inflammatory mediators in the striatum. We revealed that Rg1 exerted neuroprotective effects by suppressing 3-NP-induced activation of the MAPKs and NF-kappa Beta signaling pathways in the striatum. Thus, our results suggest that Rg1 exerts therapeutic effects on 3-NP-induced HD mouse model via suppressing MAPKs and NF-kappa Beta signaling pathways. Rg1 may be served as a novel therapeutic option for HD.