{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:41:12Z","timestamp":1792806072921,"version":"4.5.0"},"reference-count":380,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Bulgarian National Science Fund","award":["K\u03a0-06-H61\/4"],"award-info":[{"award-number":["K\u03a0-06-H61\/4"]}]},{"name":"the Bulgarian National Science Fund","award":["BG-RRP-2.017-0046-C01"],"award-info":[{"award-number":["BG-RRP-2.017-0046-C01"]}]},{"name":"Bulgaria\u2019s Recovery and Resilience Plan, a part of the European Union\u2019s NextGenerationEU instrument for the implementation of an investment under C2I2","award":["K\u03a0-06-H61\/4"],"award-info":[{"award-number":["K\u03a0-06-H61\/4"]}]},{"name":"Bulgaria\u2019s Recovery and Resilience Plan, a part of the European Union\u2019s NextGenerationEU instrument for the implementation of an investment under C2I2","award":["BG-RRP-2.017-0046-C01"],"award-info":[{"award-number":["BG-RRP-2.017-0046-C01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs\/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis affects over 20 million people, with a worldwide prevalence of 0.5\u20131.0%, exhibiting gender, ethnic, and geographical differences. The progressive disability severely impairs physical motion and quality of life and is finally leading to a shortened life span. The pathogenesis of RA is a complex and still poorly understood process in which genetic and environmental factors are principally associated. Current treatment mostly relies on conventional\/non-biological disease-modifying anti-rheumatic drugs (cDMARDs), analgesics, non-steroidal anti-inflammatory drugs, glucocorticoids, steroids, immunosuppresants, and biologic DMARDs, which only control inflammation and pain. Along with side effects (drug toxicity and intolerance), these anti-rheumatic drugs possess limited efficacy. Therefore, the discovery of novel multi-target therapeutics with an improved safety profile that function as inhibitors of RA-linked signaling systems are in high demand, and this is in the interest of both patients and clinicians. Plant-derived extracts, nutritional supplements, dietary medicine, and molecules with anti-inflammatory activity represent promising adjuvant agents or alternatives for RA therapeutics. This review not only aims to discuss the basic features of RA pathogenesis, risk factors, and signaling pathways but also highlights the research progress in pre-clinical RA in in vitro and in vivo models, revealing new avenues in the management of the disease in terms of comprehensive multidisciplinary strategies originating from medicinal plants and plant-derived molecules.<\/jats:p>","DOI":"10.3390\/ijms26146813","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T12:55:00Z","timestamp":1752670500000},"page":"6813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Therapeutic Potential of Phytochemicals Unlocks New Avenues in the Management of Rheumatoid Arthritis"],"prefix":"10.3390","volume":"26","author":[{"given":"Kalina A.","family":"Nikolova-Ganeva","sequence":"first","affiliation":[{"name":"Department of Immunology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-9296","authenticated-orcid":false,"given":"Nikolina M.","family":"Mihaylova","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9679-7976","authenticated-orcid":false,"given":"Lidiya A.","family":"Kechidzhieva","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina I.","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Laboratory of Eukaryotic Cell Biology, Department of Biotechnology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Zarkov","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Pharmacy, Sofia University, 1 James Bourchier Ave., 1164 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Parzhanov","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of Food Technologies Plovdiv, 26 Maritsa Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momchil M.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of Food Technologies Plovdiv, 26 Maritsa Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-683X","authenticated-orcid":false,"given":"Andrey S.","family":"Marchev","sequence":"additional","affiliation":[{"name":"Laboratory of Eukaryotic Cell Biology, Department of Biotechnology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Damerau, A., and Gaber, T. 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