Department of Sports Medicine, The Cangzhou City Central Hospital, 16 Xinhua Road, Yunhe Region, Cangzhou City, 061001, Hebei Province, China.
Department of Orthopedics, The Cangzhou City Central Hospital, 16 Xinhua Road, Yunhe Region, Cangzhou City, 061001, Hebei Province, China.
Immunol Res. 2018 Jun;66(3):406-413. doi: 10.1007/s12026-018-8999-2.
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)-1β, 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/β, and p65 expression than those of untreated cells. In addition, we found when cells were stimulated with IKKβ, crocin pre-treatment showed significantly inhibitory effect on the luciferase activity of IL-1β. In vivo results also showed that crocin treatment dramatically reduced plasma levels of TNF-α, IL-1β, and IL-6 in CIA mice. Crocin is efficient to suppress the productions of TNF-α, IL-6, and IL-1β by blocking NF-κB signal activation through its interaction with IKK, suggesting that crocin could be an efficient treatment for RA.
类风湿关节炎（RA）是一种系统性自身免疫性疾病，其特征是炎症细胞攻击关节导致关节不可逆破坏。最近的研究表明，西红花苷能够缓解关节炎并抑制炎症反应，这意味着西红花苷可能是一种有前途的抗关节炎药物。在这项研究中，我们通过测量存在或不存在西红花苷时脂多糖（LPS）刺激细胞因子产生的情况，证实了西红花苷对 RA 的作用，并揭示了其潜在机制。我们还在胶原诱导关节炎（CIA）的小鼠模型中测试了西红花苷的作用。结果发现，西红花苷显著抑制了 LPS 诱导的人成纤维样滑膜细胞（FLS）中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和 IL-6 的表达。我们测试了西红花苷对核因子-κB（NF-κB）信号的影响，观察到用 500 μM 西红花苷预处理的细胞中 LPS 诱导的 p-IκBα、p-IκB 激酶（IKK）α/β和 p65 表达水平低于未处理的细胞。此外，我们发现当细胞受到 IKKβ刺激时，西红花苷预处理对 IL-1β的荧光素酶活性表现出显著的抑制作用。体内结果还表明，西红花苷治疗可显著降低 CIA 小鼠血浆中 TNF-α、IL-1β和 IL-6 的水平。西红花苷通过与 IKK 相互作用阻断 NF-κB 信号激活，有效抑制 TNF-α、IL-6 和 IL-1β的产生，提示西红花苷可能是治疗 RA 的有效药物。
