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

Authors: Xiong Yang1, Shi-feng Chu1, Zhen-zhen Wang1, Fang-fang Li1, Yu-he Yuan1, Nai-hong Chen1
1 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Correspondence to: Nai-hong Chen:,
DOI: 10.1038/s41401-020-00558-4
Received: 12 June 2020
Accepted: 18 October 2020
Advance online: 19 November 2020


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·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-κΒ 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-κΒ signaling pathways. Rg1 may be served as a novel therapeutic option for HD.
Keywords: Huntington’s disease; ginsenoside Rg1; 3-nitropropionic acid; striatum; neuroprotective effects; MAPKs; NF-κB

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