Article

Rg1 improves LPS-induced Parkinsonian symptoms in mice via inhibition of NF-κB signaling and modulation of M1/M2 polarization

Authors: Jia-qi Liu1,2, Ming Zhao3, Zhao Zhang1, Li-yuan Cui1, Xin Zhou1, Wei Zhang4, Shi-feng Chu1, Da-yong Zhang2, Nai-hong Chen1
1 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
2 China Pharmaceutical University, Nanjing 210009, China
3 Beijing Hospital, Beijing 100730, China
4 Institute of Chinese Integrative Medicine Hebei Medical University, Shijiazhuang 050017, China
Correspondence to: Da-yong Zhang: cpuzdy@163.com, Nai-hong Chen: chennh@imm.ac.cn,
DOI: 10.1038/s41401-020-0358-x
Received: 25 September 2019
Accepted: 1 January 2020
Advance online: 18 March 2020

Abstract

Ginsenoside Rg1 is one of the most active ingredients in ginseng, which has been reported to protect dopaminergic neurons and improve behavioral defects in MPTP model, 6-OHDA model and rotenone model. However, it is unclear whether Rg1 exerted neuroprotection in LPS-induced sub-acute PD model. In this study, we investigated the neuroprotective effect of Rg1 in the sub-acute PD mouse model and explored the related mechanisms. Rg1 (10, 20, 40 mg·kg−1·d−1) was orally administered to mice for 18 days. A sub-acute PD model was established in the mice through LPS microinjection into the substantia nigra (SN) from D8 to D13. We found that Rg1 administration dose-dependently inhibited LPS-induced damage of dopaminergic neurons and activation of glial cells in the substantia nigra pars compacta (SNpc). The neuroprotective effects of Rg1 were associated with the reduction of pro-inflammatory cytokines and the improvement of anti-inflammatory cytokines and neurotrophin in the midbrain. Rg1 shifted the polarization of microglia towards the M2 phenotype from M1, evidenced by decreased M1 markers (inducible NO synthase, CD16, etc.) and increased M2 markers (arginase 1 (Arg1), CD206, etc) in the midbrain. Furthermore, Rg1 administration markedly inhibited nuclear translocation of NF-κB in midbrain microglia. In conclusion, Rg1 protects PD mice induced by continuous LPS injection by inhibiting the nuclear entry of NF-κB and regulating the polarization balance of microglia, shedding new light on a disease-modifying therapy of PD.
Keywords: Parkinson’s disease; ginsenoside Rg1; neuroinflammation; lipopolysaccharide; microglia polarization; NF-κB

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