Taraxasterol suppresses inflammation in IL-1β-induced rheumatoid arthritis fibroblast-like synoviocytes and rheumatoid arthritis progression in mice

Abstract

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.

Keywords: Collagen-induced arthritis; Fibroblast-like synoviocytes rheumatoid arthritis; NF-κB; NLRP3 inflammasomes; Rheumatoid arthritis; Taraxasterol.