关节炎
类风湿性关节炎
肿瘤坏死因子α
医学
炎症
基质金属蛋白酶
IκB激酶
体内
白细胞介素
促炎细胞因子
免疫学
雷公藤
细胞因子
癌症研究
NF-κB
内科学
药理学
生物
病理
生物技术
替代医学
作者
Jianfeng Chen,Wencan Wu,Miaomiao Zhang,Caiming Chen
标识
DOI:10.1016/j.intimp.2019.02.029
摘要
Previous study has indicated that taraxasterol (TAR), one of bioactive pentacyclic triterpenes mainly isolated from Chinese medicine herb Taraxacum officinale, displays considerable anti-inflammatory effects in various kinds of models. However, its effects on rheumatoid arthritis (RA) have still not been elucidated. In this study, we aim to investigate its anti-inflammatory effects and underlying mechanisms of TAR against RA using both interleukin (IL)-1β-stimulated human fibroblast-like synoviocytes rheumatoid arthritis (HFLS-RA) in vitro and collagen-induced arthritis (CIA) mice in vivo. Firstly, our results demonstrated that TRA significantly suppressed the IL-1β-induced expressions of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-6, and IL-8 and productions of matrix metalloproteinases (MMPs), like MMP-1 and MMP-3 in HFLS-RA in vitro. Moreover, TRA alleviated arthritis progressions and prevented inflammatory processes in the joint tissues of CIA mice in vivo. Further mechanism studies indicated that TRA blocked nuclear factor kappa B (NF-κB) activation via modulating inhibitor of kappa B (IκB), IκB kinase (IKK) and transforming growth factor-β-activated kinase 1 (TAK1). Results also demonstrated that TRA suppressed the NOD-like receptor protein 3 (NLRP3) inflammasomes through blocking expressions of NLRP3, apoptosis-associated speck-like protein containing (ASC), and caspase-1 in both IL-1β-induced HFLS-RA and CIA mice. In conclusions, current findings suggested that TRA might one of considerable therapeutic compounds for relieving rheumatoid arthritis progress via suppressing inflammations through modulating NF-κB and NLRP3 inflammasomes pathways.
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