{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:12:51Z","timestamp":1790187171505,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"publisher","award":["15-0308"],"award-info":[{"award-number":["15-0308"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of educatioon, science, research and sport of the Slovak Republic","award":["VEGA 2\/0136*20"],"award-info":[{"award-number":["VEGA 2\/0136*20"]}]},{"name":"Ministry of educatioon, science, research and sport of the Slovak Republic","award":["VEGA 1\/0429\/21"],"award-info":[{"award-number":["VEGA 1\/0429\/21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: Combination therapy with methotrexate (MTX) is the most common therapeutic strategy used for the treatment of patients with rheumatoid arthritis (RA). In this study, we combined the natural compound carnosic acid (CA) with MTX to reduce inflammation and oxidative stress in adjuvant arthritis (AA). Methods: AA was induced in 6\u20138 rats per group. MTX was administrated twice a week at a dose of 0.3 mg\/kg b.w., while CA was administered daily at a dose of 100 mg\/kg both in monotherapy and in combination with MTX. Plasma samples were collected on the 14th, 21st, and 28th day. Body weight and hind paw volume were measured once a week. Results: We found that, mainly, the CA + MTX combination significantly reduced the hind paw swelling, the levels of IL-17A, MMP-9, and MCP-1 in plasma, and GGT activity in joint homogenates. The mRNA expression of HO-1, catalase, and IL-1\u03b2 in the liver were significantly improved by CA + MTX only. Our results indicate that adding CA to MTX treatment could be a good therapeutic option for patients suffering from RA. Conclusions: The addition of CA to methotrexate treatment significantly improved its efficacy in decreasing the development of AA by inhibiting the markers of inflammation and oxidative stress.<\/jats:p>","DOI":"10.3390\/molecules27207115","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T08:19:06Z","timestamp":1666599546000},"page":"7115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Combination Therapy of Carnosic Acid and Methotrexate Effectively Suppressed the Inflammatory Markers and Oxidative Stress in Experimental Arthritis"],"prefix":"10.3390","volume":"27","author":[{"given":"Martin","family":"Chrastina","sequence":"first","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 5826\/9, SK-841 41 Bratislava, Slovakia"},{"name":"Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University Bratislava, Mal\u00e1 Hora 10701\/4A, SK-036 01 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvester","family":"Poni\u0161t","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 5826\/9, SK-841 41 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6417-9586","authenticated-orcid":false,"given":"Jaroslav","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University Bratislava, Odboj\u00e1rov 10, SK-832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4634-3311","authenticated-orcid":false,"given":"Szilvia","family":"Czigle","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University Bratislava, Odboj\u00e1rov 10, SK-832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-7054","authenticated-orcid":false,"given":"\u013dudmila","family":"Pa\u0161kov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University Bratislava, Odboj\u00e1rov 10, SK-832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Vyletelov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University Bratislava, Odboj\u00e1rov 10, SK-832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"\u0160v\u00edk","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 5826\/9, SK-841 41 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katar\u00edna","family":"Bauerov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 5826\/9, SK-841 41 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"669","DOI":"10.3899\/jrheum.200367","article-title":"The Prevalence of Rheumatoid Arthritis: A Systematic Review of Population-based Studies","volume":"48","author":"Almutairi","year":"2021","journal-title":"J. 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