Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 70, Issue -, Pages 274-283Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2019.02.029
Keywords
Taraxasterol; Rheumatoid arthritis; Fibroblast-like synoviocytes rheumatoid arthritis; Collagen-induced arthritis; NF-kappa B; NLRP3 inflammasomes
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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)-1 beta-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-1 beta-induced expressions of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), 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-kappa B) activation via modulating inhibitor of kappa B (I kappa B), I kappa B kinase (IKK) and transforming growth factor-beta-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-1 beta-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-kappa B and NLRP3 inflammasomes pathways.
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