{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:44:06Z","timestamp":1777445046194,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T00:00:00Z","timestamp":1630195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rheumatoid arthritis (RA) is one of the inflammatory diseases detected in more than 1% of the world population. In the present study, oxymatrine hydrazone (OMTH) was synthesized and investigated for treatment of RA in vitro in TNF\u2010\u03b1 induced fibroblast\u2010like synoviocyte cell model. Cell viability and apoptosis were detected using MTT and flow cytometry assays, respectively. ELISA was used for determination of inflammatory cytokines and western blotting for evaluation of protein expression. Pretreatment of HFLS\u2010RA cells with 0.5, 1.0, 1.5, 2.0, and 2.5\u00a0\u03bcM doses of OMTH suppressed TNF\u2010\u03b1 induced promotion of proliferative potential in dose\u2010based manner. The OMTH pretreatment of TNF\u2010\u03b1 exposed HFLS\u2010RA cells significantly increased apoptotic cell proportion. In TNF\u2010\u03b1 exposed HFLS\u2010RA cells OMTH pretreatment elevated Bax and suppressed Bcl\u20102 expression. Treatment of HFLS\u2010RA cells with OMTH prevented TNF\u2010\u03b1 mediated elevation of IL\u20101\u03b2, IL\u20106 and IL\u20108. Moreover, OMTH treatment of HFLS\u2010RA cells effectively suppressed TNF\u2010\u03b1 mediated elevated levels of MMP\u20101 and MMP\u201013. Pretreatment of HFLS\u2010RA cells with OMTH reversed TNF\u2010\u03b1 mediated promotion of iNOS and COX\u20102 levels. The MEK\/1\/2 and p65 phosphorylation in TNF\u2010\u03b1 exposed HFLS\u2010RA cells was reduced by OMTH pre\u2010treatment in dose\u2010based manner. Thus, OMTH successfully inhibited TNF\u2010\u03b1\u2010mediated increased viability of RA synovial cells and activated apoptosis. Pretreatment of TNF\u2010\u03b1 exposed synovial cells with OMTH targeted phosphorylation of MEK\/NF\u2010\u03baB. Therefore, OMTH may act as potential therapeutic agent for RA treatment.<\/jats:p>","DOI":"10.1002\/tox.23357","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T06:24:30Z","timestamp":1630304670000},"page":"2448-2453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Oxymatrine hydrazone (OMTH) synthesis and its protective effect for rheumatoid arthritis through downregulation of <scp>MEK<\/scp>\/<scp>NF\u2010\u03baB<\/scp> pathway"],"prefix":"10.1002","volume":"36","author":[{"given":"Guangwen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Arthroplasty Surgery Affiliated Hospital of Gansu University of Chinese Medicine  Lanzhou 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