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

作　　者：Jia-qi Liu Ming Zhao Zhao Zhang Li-yuan Cui Xin Zhou Wei Zhang Shi-feng Chu Da-yong Zhang Nai-hong Chen 

机构地区：[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

出　　处：《Acta Pharmacologica Sinica》2020年第4期523-534,共12页中国药理学报（英文版）

基　　金：the National Natural Science Foundation of China Grants(81503275,81973499,81603316,81873026,81730096,81172934,and 30973607);the CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-004);"Double First-Class"New Drug Development Project of China Pharmaceutical University(CPU2018PZQ15).

摘　　要：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-in?ammatory cytokines and the improvement of anti-in?ammatory 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.

关 键 词：Parkinson’s disease ginsenoside Rg1 NEUROINFLAMMATION lipopolysaccharide microglia polarization NF-ΚB 

分 类 号：R965[医药卫生—药理学]