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

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.