Anti-inflammatory effects of ursolic acid-3-acetate on human synovial fibroblasts and a murine model of rheumatoid arthritis

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Title
Anti-inflammatory effects of ursolic acid-3-acetate on human synovial fibroblasts and a murine model of rheumatoid arthritis
Author(s)
J Y Lee; J K Choi; N H Jeong; J Yoo; Y S Ha; B Lee; H Choi; P H Park; T Y Shin; T K Kwon; Sang-Rae Lee; Soyoung LeeSeung Woong LeeMun Chual Rho; S H Kim
Bibliographic Citation
International Immunopharmacology, vol. 49, pp. 118-125
Publication Year
2017
Abstract
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)-α-stimulated RA synovial fibroblasts. The oral administration of UAA showed a decrease in clinical arthritis symptoms, paw thickness, histologic and radiologic changes, and serum IgG1 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 IKKα/β, ΙκBα, and nuclear factor-κB. 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.
Keyword
Collagen-induced arthritisInflammatory cytokineLymph nodesMatrix metalloproteinaseSynovial fibroblastsUrsolic acid-3-acetate
ISSN
1567-5769
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.intimp.2017.05.028
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > National Primate Research Center > 1. Journal Articles
Jeonbuk Branch Institute > Immunoregulatory materials Research Center > 1. Journal Articles
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