Abstract
Silibinin, a natural polyphenolic flavonoid, possesses anti-oxidant, anti-inflammation and anti-cancer properties. The present study was designed to investigate the effects of silibinin on rheumatoid arthritis (RA) pathogenesis-related cells and collagen-induced arthritis (CIA) and further explore the potential underlying mechanisms. Our results showed that silibinin suppressed cell viability and increased the percentage of apoptotic RA-fibroblast-like synoviocytes (FLS). Furthermore, the production of inflammatory cytokines in RA-FLS and a CIA rat model was effectively inhibited by silibinin. Silibinin also induced macrophage M2 polarization in RAW264.7 cells. We further demonstrated that silibinin inhibits Th17 cell differentiation in vitro. The nuclear factor kappa B (NF-κB) pathway was suppressed in RA-FLS. In addition, Sirtuin1 (SIRT1) was decreased after silibinin treatment, and RA-FLS transfection with a short hairpin RNA (shRNA) of SIRT1 enhanced silibinin-induced apoptosis. Autophagy was markedly decreased in a dose-dependent manner following silibinin treatment. These findings indicate that silibinin inhibited inflammation by inhibiting the NF-κB pathway, and SIRT1 may participate in silibinin-induced apoptosis. Silibinin also inhibited autophagy in RA-FLS. Thus, silibinin may be a potential therapeutic agent for the treatment of RA.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and joint destruction[1]
Having shown potential anti-inflammation effects in vitro, we examined the therapeutic effects of silibinin in vivo using a Western blotting. (B) The intensity of Beclin-1 and LC3 was determined by densitometry using ImageJ software and normalized with the loading control (SIRT1/GAPDH)
Due to its anti-inflammation and anti-proliferation features, in the present study we explored the effects and underlying mechanisms of silibinin in rheumatoid arthritis (RA)
Summary
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and joint destruction[1]. The proliferation of fibroblast-like synoviocytes (FLS) as well as the infiltration of activated immune cells (including lymphocytes and macrophages) lead to persistent synovial inflammation and progressive joint destruction[2,3]. Immune cells, such as T lymphocytes and macrophages, produce pro-inflammatory mediators, which induce chronic inflammation in RA. Inhibiting the synthesis of inflammatory cytokines and inducing the apoptosis of proliferative FLS are therapeutic targets for RA. The most extensively studied member of the mammalian sirtuin family is SIRT1, which plays diverse roles in cell metabolism, survival, ageing, and inflammation[14,15]. Recent studies have demonstrated higher SIRT1 protein expression in whole synovial tissue and cultured FLS from the joints of patients with RA that that from patients with OA. Downregulation of SIRT1 was found to reduce the expression of pro-inflammatory mediators and induce the apoptosis of FLS16. Autophagy may be a potential therapeutic target in RA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
