Phloroglucinol derivative compound 21 attenuates cuprizoneinduced multiple sclerosis mice through promoting remyelination and inhibiting neuroinflammation  

作　　者：Zhe Zhao Xiu-qi Bao Zihong Zhang Hui Liu Dan Zhang 

机构地区：[1]State Key Laboratory of Bioactive Substrate and Function of Natural Medicine,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

出　　处：《Science China(Life Sciences)》2020年第6期905-914,共10页中国科学（生命科学英文版）

基　　金：the National Natural Sciences Foundation of China (81630097 and 81773718);the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2016I2M-3-011);the Chinese Academy of Medical Sciences Fundamental Research Funds for the Central Universities (2018RC350002);the National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Thirteenth Five-year Plan Period (2018ZX09711001003-005, 2018ZX09711001-008-005 and 2018ZX09711001-003-020)。

摘　　要：Multiple sclerosis(MS) is a chronic autoimmune demyelinating disease in the central nervous system. The myelin loss is mainly caused by dysfunction of oligodendrocytes and inflammatory responses of microglia and astrocytes further aggravate the demyelination. Current therapies for MS focus on suppressing the overactivated immune response but cannot halt the disease progress, so effective drugs are urgently needed. Compound 21 is a phloroglucinol derivative that has been proved to have an outstanding anti-inflammatory effect. The purpose of the present study is to investigate whether this novel compound is effective in MS. The cuprizone-induced model was used in this study to mimic the pathological progress of MS. The results showed that Compound 21 significantly improved the neurological dysfunction and motor coordination impairment. Luxol Fast Blue staining and myelin basic protein immunostaining demonstrated that Compound 21 remarkably promoted remyelination. In addition,Compound 21 significantly promoted oligodendrocytes differentiation. Furthermore, we found that Compound 21 decreased microglia and astrocytes activities and the subsequent neuroinflammatory response, indicating that the anti-inflammatory effect of Compound 21 was also involved in its neuro-protection. All the data prove that Compound 21 exerts protective effect on MS through promoting remyelination and suppressing neuroinflammation, indicating that Compound 21 might be a potential drug candidate for MS treatment.

关 键 词：multiple sclerosis OLIGODENDROCYTES DEMYELINATION microglia ASTROCYTES 

分 类 号：R744.51[医药卫生—神经病学与精神病学]