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In this study, we found that leonurine, a bioactive alkaloid, alleviated <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> disease severity along with reduced central nervous system inflammation and myelin damage. During the pathogenesis of <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content>, leonurine dramatically suppressed the recruitment of encephalitogenic T cells into the central nervous system, whereas did not impair periphery immune responses and microglia activation. Mechanistically, leonurine protected mice against demyelination along with enhanced remyelination through promoting the maturation of oligodendrocytes in both <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> and cuprizone\u2010induced demyelination mouse models. Moreover, we identified that the expression of demethylase jumonji domain\u2010containing protein D3 was significantly enhanced upon treatment of leonurine, which suppressed the trimethylation of histone H3 lysine\u201027 and enhanced oligodendrocyte maturation accordingly. Collectively, our study identified the therapeutic effect of leonurine on <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> model, which potentially represents a promising therapeutic strategy for multiple sclerosis, even other demyelination disorders.<\/jats:p>","DOI":"10.1111\/jcmm.14053","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T03:04:26Z","timestamp":1545015866000},"page":"1470-1485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Leonurine suppresses neuroinflammation through promoting oligodendrocyte maturation"],"prefix":"10.1111","volume":"23","author":[{"given":"Min","family":"Jin","sequence":"first","affiliation":[{"name":"Medical College of Soochow University Soochow University Suzhou Jiangsu China"},{"name":"Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 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