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The aim of this study was to investigate the therapeutic effect of <jats:styled-content style=\"fixed-case\">MSL<\/jats:styled-content> in mice with collagen\u2010induced arthritis (<jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content>) and explore its underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The anti\u2010arthritic effects of <jats:styled-content style=\"fixed-case\">MSL<\/jats:styled-content> were evaluated on human rheumatoid fibroblast\u2010like synoviocytes (<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>) <jats:italic>in vitro<\/jats:italic> and <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content> in mice <jats:italic>in vivo<\/jats:italic> by obtaining clinical scores, measuring hind paw thickness and inflammatory cytokine levels, radiographic evaluations and histopathological assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Treatment with <jats:styled-content style=\"fixed-case\">MSL<\/jats:styled-content> after the onset of arthritis significantly prevented the progression and development of rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>) in <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content> mice without megascopic gastric mucosa damage. In addition, <jats:styled-content style=\"fixed-case\">MSL<\/jats:styled-content> inhibited the production of pro\u2010inflammatory mediators, the phosphorylation and translocation of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B,<\/jats:styled-content> and cell proliferation induced by <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 in <jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">MSL<\/jats:styled-content> non\u2010selectively inhibited the activity of <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u2005<jats:italic>in vitro,<\/jats:italic> but was a more potent inhibitor of COX\u20102 than COX\u20101. <jats:styled-content style=\"fixed-case\">MSL<\/jats:styled-content> also inhibited the phosphorylation of inhibitor of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> kinase, <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>\u03b1 and p65, thus blocking the nuclear translocation of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1\u2010stimulated <jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">MSL<\/jats:styled-content> exerts therapeutic effects on <jats:styled-content style=\"fixed-case\">CIA<\/jats:styled-content> mice, suppressing the inflammatory response and joint destruction by non\u2010selectively inhibiting the activity of COX and suppressing activation of the NF\u2010\u03baB signalling pathway, but without damaging the gastric mucosa. Therefore, <jats:styled-content style=\"fixed-case\">MSL<\/jats:styled-content> has great potential to be developed into a novel therapeutic agent for the treatment of <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12715","type":"journal-article","created":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T11:11:42Z","timestamp":1396955502000},"page":"3526-3538","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Methyl salicylate lactoside inhibits inflammatory response of fibroblast\u2010like synoviocytes and joint destruction in collagen\u2010induced arthritis in mice"],"prefix":"10.1111","volume":"171","author":[{"given":"Wenyu","family":"Xin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences &amp; Peking Union 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