Myelin damage and abnormal remyelination processes lead to central nervous system dysfunction.Glial activation-induced microenvironment changes are characteristic features of the diseases with myelin abnormalities.We previously showed that ginsenoside Rg1,a main component of ginseng,ameliorated MPTP-mediated myelin damage in mice,but the underlying mechanisms are unclear.In this study we investigated the effects of Rg1 and mechanisms in cuprizone(CPZ)-induced demyelination mouse model.Mice were treated with CPZ solution(300mg·kg-1·d-1,ig)for 5 weeks;from week 2,the mice received Rg1(5,10,and 20 mg·kg-1·d-1,ig)for 4 weeks.We showed that Rg1 administration dose-dependently alleviated bradykinesia and improved CPZ-disrupted motor coordination ability in CPZ-treated mice.Furthermore,Rg1 administration significantly decreased demyelination and axonal injury in pathological assays.We further revealed that the neuroprotective effects of Rg1 were associated with inhibiting CXCL10-mediated modulation of glial response,which was mediated by NF-KB nuclear translocation and CXCL10 promoter activation.In microglial cell line BV-2,we demonstrated that the effects of Rg1 on pro-inflammatory and migratory phenotypes of microglia were related to CXCL10,while Rg1-induced phagocytosis of microglia was not directly related to CXCL10.In CPZ-induced demyelination mouse model,injection of AAV-CXCL10 shRNA into mouse lateral ventricles 3 weeks prior CPZ treatment occluded the beneficial effects of Rg1 administration in behavioral and pathological assays.In conclusion,CXCL10 mediates the protective role of Rg1 in CPZ-induced demyelination mouse model.This study provides new insight into potential disease-modifying therapies for myelin abnormalities.

Yi-xiao Dong;Shi-feng Chu;Sha-sha Wang;Ya-juan Tian;Wen-bin He;Yu-sheng Du;Zhen-zhen Wang;Xu Yan;Zhao Zhang;Nai-hong Chen

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica&Neuroscience Center,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100050,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Shanxi Key Laboratory of Chinese Medicine Encephalopathy,Shanxi University of Chinese Medicine,Jinzhong 030619,China

中国药理学报（英文版）

[1]Yi-xiao Dong;Shi-feng Chu;Sha-sha Wang;Ya-juan Tian;Wen-bin He;Yu-sheng Du;Zhen-zhen Wang;Xu Yan;Zhao Zhang;Nai-hong Chen-.Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response)[J].中国药理学报（英文版）,2022(03):563-576

bradykinesia

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