RESUMO
Rheumatoid arthritis (RA) is a systemic autoimmune disease, characterized by the irreversible joint destruction resulted from the attack of inflammatory cells to the joints. Recent studies demonstrated that crocin is able to alleviate arthritis and suppress inflammatory responses, implying crocin as a potential promising antiarthritic agent. In this study, we confirmed the effect of crocin on RA and revealed its underlying mechanism by measuring lipopolysaccharides (LPS)-stimulated cytokine production in presence or absence of crocin. The effect of crocin was also tested in vivo using a mouse model of collagen-induced arthritis (CIA). It was found that crocin significantly repressed the LPS-induced expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in human fibroblast-like synoviocytes (FLS). We tested the effect of crocin on nuclear factor-kappa B (NF-κB) signaling and observed that cells pre-treated with 500 µM of crocin exhibited lower levels of LPS-induced p-IκBα, p-IκB kinase (IKK) α/ß, and p65 expression than those of untreated cells. In addition, we found when cells were stimulated with IKKß, crocin pre-treatment showed significantly inhibitory effect on the luciferase activity of IL-1ß. In vivo results also showed that crocin treatment dramatically reduced plasma levels of TNF-α, IL-1ß, and IL-6 in CIA mice. Crocin is efficient to suppress the productions of TNF-α, IL-6, and IL-1ß by blocking NF-κB signal activation through its interaction with IKK, suggesting that crocin could be an efficient treatment for RA.
