3,3′-Diindolylmethane attenuates experimental arthritis and osteoclastogenesis
3,3′-Diindolylmethane attenuates experimental arthritis and osteoclastogenesis
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DOI：
10.1016/j.bcp.2009.10.010
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发表时间：
2010-03-01
影响因子：
5.8
通讯作者：
Zhang, Junfeng
中科院分区：
文献类型：
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作者：
Dong, Lei;Xia, Suhua;Zhang, Junfeng
3，3 '-二吲哚基甲烷（DIM）是芸苔属食用植物中存在的葡萄糖芸苔素在自溶过程中形成的天然化合物。本研究旨在探讨DIM对实验性关节炎的治疗作用。采用大鼠佐剂性关节炎（AIA）模型，通过每日AIA足肿胀观察和组织学/放射学分析，检查DIM对实验性关节炎的影响。为了阐明其作用的可能机制，随后分析了血清细胞因子水平以及感染组织中核因子κ B配体（RANKL）受体激活剂的表达。在内毒素诱导的骨吸收（EIBR）小鼠模型和成纤维细胞样细胞和成骨细胞的体外培养物中进一步研究了DIM对破骨细胞生成的影响，并对RANKL表达进行了评价。通过炎症和组织损伤的临床和组织学指标判断，在动物模型中，DIM的给药被证明可以减弱AIA。一方面，DIM可以减少几种炎性细胞因子的表达，但这不足以阻止关节炎的发展。另一方面，DIM显示出有效抑制RANKL的表达，导致破骨细胞生成的阻断，从而减轻实验性关节炎。进一步的体外和体内研究证实了DIM对RANKL的抑制作用。DIM通过抑制RANKL的表达在动物模型中显示出抗关节炎活性，因此可能为关节炎和相关疾病提供潜在的治疗。(c)2009 Elsevier Inc. All rights reserved.
3,3'-Diindolylmethane (DIM) is a natural compound formed during the autolysis of glucobrassicin present in Brassica food plants. This study aimed to investigate the therapeutic efficacies of DIM on experimental arthritis. The effects of DIM on experimental arthritis were examined on a rat model of adjuvant-induced arthritis (AIA), with daily AIA paw swelling observation and histological/radiographic analysis. To elucidate the possible mechanisms of its action, serum cytokine levels as well as the expression of receptor activator for nuclear factor kappa B ligand (RANKL) in infected tissues were subsequently analyzed. The impact of DIM on osteoclastogenesis was further investigated on a mouse model of endotoxin-induced bone resorption (EIBR) and in vitro cultures of fibroblast-like cells and osteoblasts, with RANKL expression being evaluated with great interest. The administration of DIM was demonstrated to attenuate AIA in animal models, as judged by clinical and histologic indices of inflammation and tissue damage. On the one hand, DIM could reduce the expression of several inflammatory cytokines, which was, however, not adequate to prevent the development of the arthritis. On the other hand, DIM was shown to effectively inhibit the expression of RANKL, leading to the blockade of osteoclastogenesis and consequently an alleviation of experimental arthritis. Further in vitro and in vivo studies confirmed the inhibition of RANKL by DIM. DIM has shown anti-arthritis activity in animal models via inhibiting the expression of RANKL, and thus may offer potential treatments for arthritis and associated disorders. (c) 2009 Elsevier Inc. All rights reserved.