Department of Outpatient Pharmacy, The First People's Hospital of Wenling, Wenling 317500, Zhejiang, China.
Department of Pharmacy, The First People's Hospital of Wenling, Wenling 317500, Zhejiang, China.
Int Immunopharmacol. 2019 May;70:274-283. doi: 10.1016/j.intimp.2019.02.029. Epub 2019 Mar 6.
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.
先前的研究表明，蒲公英甾醇（TAR）是从中药蒲公英中主要分离得到的一种生物活性五环三萜，在各种模型中均表现出相当强的抗炎作用。然而，其对类风湿关节炎（RA）的作用尚未阐明。本研究旨在通过体外白细胞介素（IL）-1β刺激的人成纤维样滑膜细胞类风湿关节炎（HFLS-RA）和体内胶原诱导性关节炎（CIA）小鼠模型，研究 TAR 对 RA 的抗炎作用及其机制。首先，我们的研究结果表明，TAR 显著抑制了 IL-1β诱导的促炎细胞因子，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8），以及基质金属蛋白酶（MMPs），如 MMP-1 和 MMP-3 在体外的表达。此外，TAR 缓解了 CIA 小鼠的关节炎进展，并防止了关节组织中的炎症过程。进一步的机制研究表明，TAR 通过调节 IκB、IκB 激酶（IKK）和转化生长因子-β激活激酶 1（TAK1）来阻断核因子-κB（NF-κB）的激活。结果还表明，TAR 通过抑制 NLRP3、凋亡相关斑点样蛋白（ASC）和 caspase-1 在 IL-1β诱导的 HFLS-RA 和 CIA 小鼠中的表达，抑制了 NLRP3 炎性小体。总之，目前的研究结果表明，TAR 可能是一种通过调节 NF-κB 和 NLRP3 炎性小体途径抑制炎症来缓解类风湿关节炎进展的有前途的治疗化合物。
