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Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (\n RA<\/jats:styled-content>\n ). The aim of the study was to examine the effect of N\u2010feruloylserotonin (N\u2010f\u20105\n HT<\/jats:styled-content>\n ) and methotrexate (\n MTX<\/jats:styled-content>\n ) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats. Adjuvant arthritis was induced by intradermal injection of\n Mycobacterium\u00a0butyricum<\/jats:italic>\n in incomplete Freund\u2032s adjuvant in Lewis rats. The experiment included healthy animals, arthritic animals without any drug administration, arthritic animals with administration of N\u2010f\u20105\n HT<\/jats:styled-content>\n in the oral daily dose of 15\u00a0mg\/kg b.w., arthritic animals with administration of\n MTX<\/jats:styled-content>\n in the oral dose of 0.3\u00a0mg\/kg b.w. twice a week and arthritic animals treated with the combination of N\u2010f\u20105\n HT<\/jats:styled-content>\n and\n MTX<\/jats:styled-content>\n . N\u2010f\u20105\n HT<\/jats:styled-content>\n in monotherapy reduced only activation of\n NF<\/jats:styled-content>\n \u2010\u03baB and did not have any significant effect on other parameters monitored. Low\u2010dose treatment of\n MTX<\/jats:styled-content>\n decreased the level of\n IL<\/jats:styled-content>\n \u20101\u03b2 and\n MCP<\/jats:styled-content>\n \u20101 on day 14 and activation of\n NF<\/jats:styled-content>\n \u2010\u03baB in liver without significant effect on other parameters. N\u2010f\u20105\n HT<\/jats:styled-content>\n and\n MTX<\/jats:styled-content>\n combination showed both the anti\u2010arthritic (hind paw volume and arthritic score) and anti\u2010inflammatory effect (plasmatic levels of\n IL<\/jats:styled-content>\n \u20101\u03b2,\n IL<\/jats:styled-content>\n \u201017,\n MCP<\/jats:styled-content>\n \u20101,\n CRP<\/jats:styled-content>\n , and activation of\n NF<\/jats:styled-content>\n \u2010\u03baB in liver). In combination with\n MTX<\/jats:styled-content>\n , N\u2010f\u20105\n HT<\/jats:styled-content>\n markedly potentiated the therapeutic effect of\n MTX<\/jats:styled-content>\n low dose, which resulted in significant improvement of all parameters measured. The findings showed that the combination therapy simultaneously decreased multiple markers of inflammation, a result crucial for future therapy of\n RA<\/jats:styled-content>\n .\n <\/jats:p>","DOI":"10.1111\/fcp.12085","type":"journal-article","created":{"date-parts":[[2014,6,11]],"date-time":"2014-06-11T13:27:14Z","timestamp":1402493234000},"page":"616-626","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["N\u2010feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis"],"prefix":"10.1111","volume":"28","author":[{"given":"Viera","family":"Kuncirova","sequence":"first","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology Slovak Academy of Sciences Dubravska cesta 9 SK\u2010841 04 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvester","family":"Ponist","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology Slovak Academy of Sciences Dubravska cesta 9 SK\u2010841 04 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danica","family":"Mihalova","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology Slovak Academy of Sciences Dubravska cesta 9 SK\u2010841 04 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frantisek","family":"Drafi","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology Slovak Academy of Sciences Dubravska cesta 9 SK\u2010841 04 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radomir","family":"Nosal","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology Slovak Academy of Sciences Dubravska cesta 9 SK\u2010841 04 Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Acquaviva","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine University of Siena via A. 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