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茶黄素-3,3'-二没食子酸酯通过核因子-κB 和 MAPK 通路减轻小鼠类风湿性炎症。

Theaflavin-3, 3'-Digallate Attenuates Rheumatoid Inflammation in Mice Through the Nuclear Factor-κB and MAPK Pathways.

机构信息

Department of Rheumatic Immunology, Daqing Oilfield General Hospital, No. 9 Zhongkang Road, Daqing, 163000, Heilongjiang, China.

出版信息

Arch Immunol Ther Exp (Warsz). 2019 Jun;67(3):153-160. doi: 10.1007/s00005-019-00536-7. Epub 2019 Mar 14.

DOI:10.1007/s00005-019-00536-7
PMID:30874838
Abstract

Rheumatoid arthritis (RA) is a common autoimmune disease which impacts a large number of patients worldwide, and new drugs are required for lower the disease burden. Theaflavin-3, 3'-digallate (TFDG) is polyphenol exhibiting inhibition on inflammatory factors. This study aimed to explore the attenuation of TFDG on RA. The collagen-induced arthritis (CIA) mouse model was established and administered with TFDG. The arthritis score and incidence was recorded to assess the amelioration of TFDG on arthritis. Histopathological change of the mouse joint tissues was evaluated by haemotoxylin and eosin staining. The expression of pro-inflammatory mediators including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 was quantified by ELISA. The activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways in the synovium were determined by Western blotting. In comparison with the control, administration of TFDG significantly reduced arthritis score and incidence in the CIA mouse model. TFDG significantly suppressed the expression of IL-1β, TNF-α, and IL-6, as well as the levels of MMP-1, MMP-2, and MMP-3 in the synovium. TFDG also showed remarkable inhibition on the activation of NF-κB and the phosphorylation of P38, JNK2, and ERK. This study puts up evidence that TFDG exerts protection on RA via inhibiting the activation of NF-κB- and MAPK-signaling pathways.

摘要

类风湿关节炎(RA)是一种常见的自身免疫性疾病,影响全球大量患者,需要新的药物来降低疾病负担。茶黄素-3,3'-二没食子酸酯(TFDG)是一种具有抑制炎症因子作用的多酚。本研究旨在探讨 TFDG 对 RA 的缓解作用。建立胶原诱导性关节炎(CIA)小鼠模型,并给予 TFDG。记录关节炎评分和发生率,以评估 TFDG 对关节炎的改善作用。通过苏木精和伊红染色评估小鼠关节组织的组织病理学变化。通过 ELISA 定量测定促炎介质白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α和 IL-6 的表达。通过 Western blot 测定 NF-κB 和丝裂原活化蛋白激酶(MAPK)信号通路在滑膜中的激活。与对照组相比,TFDG 给药显著降低 CIA 小鼠模型的关节炎评分和发生率。TFDG 显著抑制了 IL-1β、TNF-α和 IL-6 的表达,以及滑膜中 MMP-1、MMP-2 和 MMP-3 的水平。TFDG 还对 NF-κB 和 P38、JNK2 和 ERK 的磷酸化的激活表现出显著的抑制作用。本研究为 TFDG 通过抑制 NF-κB 和 MAPK 信号通路的激活对 RA 发挥保护作用提供了证据。

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