Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response  

作　　者：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 

机构地区：[1]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 [2]Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China [3]Shanxi Key Laboratory of Chinese Medicine Encephalopathy,Shanxi University of Chinese Medicine,Jinzhong 030619,China

出　　处：《Acta Pharmacologica Sinica》2022年第3期563-576,共14页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(81973499,81873026,81730096,82074044,81773924,and 81960729);the CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-004);the Opening Program of the Shanxi Key Laboratory of Chinese Medicine Encephalopathy(CME-OP-2017001);the High-End Foreign Experts Introduction Program(G20200001485).

摘　　要：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(300 mg·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-κB 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.

关 键 词：DEMYELINATION ginsenoside Rg1 CUPRIZONE glial response CXCL10 

分 类 号：R965[医药卫生—药理学]