{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T09:01:05Z","timestamp":1777712465888,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011002","name":"national natural science foundation of china-yunnan joint fund","doi-asserted-by":"publisher","award":["81973730"],"award-info":[{"award-number":["81973730"]}],"id":[{"id":"10.13039\/501100011002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014718","name":"innovative research group project of the national natural science foundation of china","doi-asserted-by":"publisher","award":["81773922"],"award-info":[{"award-number":["81773922"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"natural science foundation of shanghai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunopathol Pharmacol"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                    Betulinic acid (BA) inhibits the migration, invasion, and cytoskeletal reorganization of fibroblast-like synoviocytes (RA-FLS) in patients with rheumatoid arthritis. Here, to further explore the mechanism of action of BA in collagen-induced arthritis (CIA) rats, we investigated the pharmacodynamic effects of BA on synovial inflammation in a rat model of type II CIA. After inducing hind paw swelling, the rats were divided into four groups: healthy controls (normal), and rats that underwent CIA and received methotrexate treatment (MTX), BA treatment (BA), or no treatment (CIA). Body weight and hind paw swelling were determined regularly, and arthritis scores were calculated weekly. On day 35, rats were sacrificed and their hind ankle joints sectioned and stained with hematoxylin and eosin for histopathological evaluation. BA significantly reduced CIA-induced hind paw swelling, synovial tissue proliferation, cartilage destruction, and vasospasm. BA treatment also decreased serum interleukin (IL)-1\u03b2, IL-6, and tumor necrosis factor-alpha (TNF-\u03b1) levels in rats with CIA. The CCK-8 assay was used to detect the proliferation of isolated vimentin\n                    <jats:sup>+<\/jats:sup>\n                    CD68\n                    <jats:sup>\u2212<\/jats:sup>\n                    RA-FLS; RA-FLS were stimulated with TNF-\u03b1 in vitro. BA significantly inhibited TNF-\u03b1-stimulated RA-FLS proliferation, as well as IL-1\u03b2 and IL-6 secretion. BA also downregulated the transcription of vascular endothelial growth factor (VEGF) and transforming growth factor \u03b2 (TGF-\u03b2) and decreased the expression of the NF-\u043aB pathway proteins (NF-kB-P65, IkB\u03b1, and IKK\u03b1\/\u03b2) in the TNF-\u03b1-stimulated RA-FLS. These results indicate that BA alleviated the symptoms of CIA by inhibiting synoviocyte proliferation, modifying TNF-\u03b1- and NF-\u043aB-related inflammatory pathways, and downregulating inflammatory mediators and growth factors including IL-1\u03b2, IL-6, VEGF, and TGF-\u03b2.\n                  <\/jats:p>","DOI":"10.1177\/2058738420945078","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T22:58:20Z","timestamp":1595890700000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Effects of betulinic acid on synovial inflammation in rats with collagen-induced arthritis"],"prefix":"10.1177","volume":"34","author":[{"family":"Kun-Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Yi","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Rheumatoid Department, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5274-6221","authenticated-orcid":false,"given":"Ying","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"bibr1-2058738420945078","first-page":"4693870","volume":"870","author":"Meyer PW","year":"2019","journal-title":"Mediators of inflammation"},{"key":"bibr2-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1038\/nri2094"},{"key":"bibr3-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00859.x"},{"key":"bibr4-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes031"},{"key":"bibr5-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-017-1027-5"},{"key":"bibr6-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-014-9837-x"},{"key":"bibr7-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.10.038"},{"key":"bibr8-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000000066"},{"key":"bibr9-2058738420945078","doi-asserted-by":"crossref","first-page":"7379893","DOI":"10.1155\/2018\/7379893","volume":"2018","author":"Jian-Ying W","year":"2018","journal-title":"Evidence-Based Complementary and Alternative Medicine"},{"key":"bibr10-2058738420945078","first-page":"570","volume":"30","author":"Xing S","year":"2019","journal-title":"China Pharmacy"},{"key":"bibr11-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3735"},{"key":"bibr12-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2015.01.001"},{"key":"bibr13-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1007\/BF02994763"},{"key":"bibr14-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.09.009"},{"key":"bibr15-2058738420945078","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.06.053"},{"key":"bibr16-2058738420945078","unstructured":"Zhen Qiu S, Yong Yong X (2019) Medical Statistics, 4th edn. 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