Triptolide, a diterpenoid triepoxide, suppresses inflammation and cartilage destruction in collagen-induced arthritis mice
Triptolide, a diterpenoid triepoxide, suppresses inflammation and cartilage destruction in collagen-induced arthritis mice
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DOI：
10.1016/j.bcp.2006.08.027
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发表时间：
2007-01-01
影响因子：
5.8
通讯作者：
Ito, Akira
中科院分区：
文献类型：
--
作者：
Lin, Na;Liu, Chunfang;Ito, Akira
中国草药治疗雷公藤。F.已经报道了在类风湿性关节炎（RA）的治疗中治疗有效的雷公藤多甙（TWHF），但其体内作用尚未阐明。本研究旨在探讨雷公藤内酯醇（雷公藤内酯醇）对胶原诱导关节炎（CIA）模型小鼠炎症和软骨破坏的影响。组织学检查显示雷公藤甲素显著减轻关节组织的炎症反应和软骨损伤。有趣的是，雷公藤甲素干扰CIA增强的基质金属蛋白酶-13和-3的表达，这被认为是软骨病理性破坏的关键酶，同时增强CIA减少的金属蛋白酶-1和-2的组织抑制剂在关节中的表达。此外，雷公藤内酯醇通过选择性抑制环氧合酶（考克斯）-2而非考克斯-1的产生和基因表达来抑制前列腺素E-2的产生。白细胞介素（IL）-1 β、肿瘤坏死因子α水平。雷公藤内酯醇还可降低关节组织和血清中IL-6的表达，并抑制CIA介导的关节中IL-6 mRNA的表达。此外，雷公藤内酯醇治疗在体内能够减少核因子-κ B，转录因子密切相关的炎症过程中，在关节软骨和滑膜CIA小鼠的丰度。这些结果表明，雷公藤甲素发挥新的软骨保护和抗炎作用，RA和雷公藤对RA的治疗作用，部分是由于雷公藤甲素的活动。(c)2006年爱思唯尔公司All rights reserved.
Chinese herbal remedy Tripterygium wilfordii Hook. f. (TWHF) has been reported to be therapeutically efficacious in the treatment of rheumatoid arthritis (RA), but its in vivo actions have not been clarified. The purpose of this study was to investigate the effects of triptolide, a diterpenoid triepoxide extracted from TWHF, on inflammation and cartilage destruction in Collagen-induced arthritis (CIA) model mice. Histological examination demonstrated that triptolide significantly reduced the inflammatory responses and cartilage damage in the joint tissues. Interestingly, triptolide interfered with CIA-augmented expression of matrix metalloproteinases-13 and -3, which are considered to be key enzymes in the pathological destruction of cartilage, and simultaneously augmented CIA-reduced tissue inhibitors of metalloproteinases-1 and -2 expression in the joints. Moreover, triptolide inhibited prostaglandin E-2 production via selective suppression of the production and gene expression of cyclooxygenase (COX)-2, but not COX-1. The levels of interleukin (IL)-1 beta, tumor necrosis factor a. and IL-6 were also decreased by triptolide in the joint tissues and sera as well as the suppression of CIA-mediated expression of their mRNAs in the joints. In addition, triptolide treatment in vivo was able to reduce an abundance of nuclear factor-kappa B, the transcriptional factor closely related to the inflammatory process, in articular cartilage and synovium in CIA mice. These results suggest that triptolide exerts novel chondroprotective and anti-inflammatory effects on RA, and the therapeutic action of TWHF on RA is, in part, due to the triptolide activities. (c) 2006 Elsevier Inc. All rights reserved.