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

作者：Lee Jong Yeong; Choi Jin Kyeong; Jeong Na Hee; Yoo Jeongsoo; Ha Yeong Su; Lee Byungheon; Choi Hyukjae; Park Pil Hoon; Shin Tae Yong; Kwon Taeg Kyu; Lee Sang Rae; Lee Soyoung; Lee Seung Woong; Rho Mun Chual; Kim Sang Hyun^*

来源：International Immunopharmacology, 2017, 49: 118-125.

DOI：10.1016/j.intimp.2017.05.028

• Collagen-induced arthritis
• Synovial fibroblasts
• Ursolic acid-3-acetate
• Matrix metalloproteinase
• Lymph nodes
• Inflammatory cytokine

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.

• 出版日期2017-8
• 单位NIH