Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 49, Issue -, Pages 118-125Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2017.05.028
Keywords
Collagen-induced arthritis; Synovial fibroblasts; Ursolic acid-3-acetate; Matrix metalloproteinase; Lymph nodes; Inflammatory cytokine
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Funding
- National Research Foundation of Korea grant - Korean Government [2014R1A5A2009242, 2012M3A9B6055416, 2016R1A2B4008513]
- KRIBB Research Initiative Program [KGM4251723, KGM2221723]
- National Research Foundation of Korea [2012M3A9B6055416, 2016R1A2B4008513] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Ursolic acid (UA), a pentacyclic triterpenoid, is a common natural substance known to be effective in the treatment of inflammation, oxidative stress, and ulcers in arthritis. This study examined the effects of ursolic acid-3-acetate (UAA), a derivative of UA, on rheumatoid arthritis (RA) and verified the underlying mechanism of action by using a type-II collagen-induced arthritis (CIA) mice model and tumor necrosis factor (TNF)-alpha-stimulated RA synovial fibroblasts. The oral administration of UAA showed a decrease in clinical arthritis symptoms, paw thickness, histologic and radiologic changes, and serum IgGl and IgG2a levels. UAA administration reduced Th1/Th17 phenotype CD4(+) T lymphocyte expansion and inflammatory cytokine production in draining lymph nodes. In addition, UAA effectively reduced the expression and production of inflammatory mediators, including cytokines and matrix metalloproteinase-1/3 in the knee joint tissue and RA synovial fibroblasts, through the downregulation of IKK alpha/beta, I kappa B alpha, and nuclear factor-kappa B. Our findings showed that UAA modulated helper T cell immune responses and matrix-degrading enzymes. The effects of UAA were comparable with those of the positive control drug, dexamethasone. In summary, all the evidence presented in this paper suggest that UAA could be a therapeutic candidate for the treatment of RA.
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