{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T21:39:53Z","timestamp":1780522793442,"version":"3.54.1"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T00:00:00Z","timestamp":1525305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous studies have shown that the natural diterpene compound, sclareol, potentially inhibits inflammation, but it has not yet been determined whether sclareol can alleviate inflammation associated with rheumatoid arthritis (RA). Here, we utilized human synovial cell line, SW982, and an experimental murine model of rheumatoid arthritis, collagen-induced arthritis (CIA), to evaluate the therapeutic effects of sclareol in RA. Arthritic DBA\/1J mice were dosed with 5 and 10 mg\/kg sclareol intraperitoneally every other day over 21 days. Arthritic severity was evaluated by levels of anti-collagen II (anti-CII) antibody, inflammatory cytokines, and histopathologic examination of knee joint tissues. Our results reveal that the serum anti-CII antibody, cytokines interleukin (IL)-1\u03b2, IL-6, tumor necrosis factor (TNF)-\u03b1, and IL-17, as well as Th17 and Th1 cell population in inguinal lymph nodes, were significantly lower in sclareol-treated mice compared to the control group. Also, the sclareol treatment groups showed reduced swelling in the paws and lower histological arthritic scores, indicating that sclareol potentially mitigates collagen-induced arthritis. Furthermore, IL-1\u03b2-stimulated SW982 cells secreted less inflammatory cytokines (TNF-\u03b1 and IL-6), which is associated with the downregulation of p38-mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and NF-\u03baB pathways. Overall, we demonstrate that sclareol could relieve arthritic severities by modulating excessive inflammation and our study merits the pharmaceutical development of sclareol as a therapeutic treatment for inflammation associated with RA.<\/jats:p>","DOI":"10.3390\/ijms19051351","type":"journal-article","created":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T03:08:21Z","timestamp":1525403301000},"page":"1351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Therapeutic Potential of Sclareol in Experimental Models of Rheumatoid Arthritis"],"prefix":"10.3390","volume":"19","author":[{"given":"Sen-Wei","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan"},{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chia","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiming","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Processing and Application of Catalytic Materials, College of Chemical Engineering, Huanggang Normal University, Huanggang 438000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-5937","authenticated-orcid":false,"given":"Shih-Chao","family":"Lin","sequence":"additional","affiliation":[{"name":"National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA"},{"name":"Institute of Biomedical Science, National Chung-Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin W.","family":"Lehman","sequence":"additional","affiliation":[{"name":"National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher Z.","family":"Lien","sequence":"additional","affiliation":[{"name":"Biodefense Program, Schar School of Policy and Government, George Mason University, Fairfax, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Chien","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Science, National Chung-Hsing University, Taichung 40227, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13075-017-1303-3","article-title":"Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis","volume":"19","author":"Bustamante","year":"2017","journal-title":"Arthritis Res. 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