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
CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Int Immunopharmacol. 2017 Aug;49:118-125. doi: 10.1016/j.intimp.2017.05.028. Epub 2017 Jun 1.
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.
熊果酸（UA）是一种五环三萜类化合物，是一种常见的天然物质，已知对治疗关节炎中的炎症、氧化应激和溃疡有效。本研究检测了UA的衍生物熊果酸-3-乙酸酯（UAA）对类风湿性关节炎（RA）的影响，并通过使用II型胶原诱导的关节炎（CIA）小鼠模型和肿瘤坏死因子（TNF）-α刺激的RA滑膜成纤维细胞验证了其潜在作用机制。口服UAA可使临床关节炎症状、爪厚度、组织学和放射学变化以及血清IgG1和IgG2a水平降低。给予UAA可减少引流淋巴结中Th1/Th17表型CD4 T淋巴细胞的扩增和炎性细胞因子的产生。此外，UAA通过下调IKKα/β、ΙκBα和核因子-κB，有效降低了膝关节组织和RA滑膜成纤维细胞中炎性介质的表达和产生，包括细胞因子和基质金属蛋白酶-1/3。我们的研究结果表明，UAA可调节辅助性T细胞免疫反应和基质降解酶。UAA的作用与阳性对照药物地塞米松相当。总之，本文提供的所有证据表明，UAA可能是治疗RA的候选药物。
