Department of Immunology, Medical College of Nanchang University, Nanchang 330000, China.
Department of Vascular Surgery, The First Hospital of Jilin University, Changchun 130000, China.
Int Immunopharmacol. 2019 Jul;72:292-300. doi: 10.1016/j.intimp.2019.04.027. Epub 2019 Apr 17.
Curcumin is a natural herbal product that has been popularly used to treat autoimmune diseases in China; however, its effects on rheumatoid arthritis and its mechanism are not clear. The main purposes of this study are to explore the therapeutic effects of curcumin on collagen-induced arthritis (CIA) rats and the pharmacological mechanism. In the present study, CIA rats were established by injecting bovine type II collagen. Curcumin and methotrexate were then orally administered daily, and the swelling degree of the hind limb joints was scored every two days. Histopathological changes were observed by hematoxylin-eosin staining. The levels of cytokines (TNF-α, IL-1β, IL-17 and TGF-β) were detected by radioimmunoassay, while the expression of IκBα and COX-2 was detected by Western blot. In addition, cell viability was detected by CCK-8 assay, and the effect of curcumin on macrophage apoptosis was detected by flow cytometry and TUNEL assay. The results indicated that in vivo curcumin attenuated the degree of joint swelling of rats and the further development of joint histopathology. Moreover, it downregulated the levels of cytokines. In vitro curcumin inhibited the degradation of IκBα and reduced the production of COX-2 in LPS-induced inflammatory RAW264.7 cells. Importantly, curcumin significantly induced macrophage apoptosis. In conclusion, in this study, we have demonstrated that curcumin exerts therapeutic effects on arthritis in CIA rats and has a strong pharmacological activity on reducing the inflammatory response in macrophages. Its mechanism may be related to the inhibition of the NF-κB signaling pathway and the promotion of macrophage apoptosis.
姜黄素是一种天然草药产品，在中国已被广泛用于治疗自身免疫性疾病；然而，其对类风湿关节炎的作用及其机制尚不清楚。本研究的主要目的是探讨姜黄素对胶原诱导性关节炎（CIA）大鼠的治疗作用及其药理机制。本研究通过注射牛 II 型胶原建立 CIA 大鼠模型，每日给予姜黄素和甲氨蝶呤灌胃，每两天对后肢关节肿胀程度进行评分，采用苏木精-伊红（HE）染色观察组织病理学变化，放射免疫法检测细胞因子（TNF-α、IL-1β、IL-17 和 TGF-β）水平，Western blot 检测 IκBα和 COX-2 的表达。此外，通过 CCK-8 检测细胞活力，通过流式细胞术和 TUNEL 检测姜黄素对巨噬细胞凋亡的影响。结果表明，体内姜黄素可减轻大鼠关节肿胀程度和关节组织病理学的进一步发展，下调细胞因子水平。体外姜黄素抑制 LPS 诱导的炎症 RAW264.7 细胞中 IκBα的降解，减少 COX-2 的产生。重要的是，姜黄素可显著诱导巨噬细胞凋亡。总之，在这项研究中，我们已经证明姜黄素对 CIA 大鼠的关节炎具有治疗作用，并且对降低巨噬细胞炎症反应具有很强的药理活性。其机制可能与抑制 NF-κB 信号通路和促进巨噬细胞凋亡有关。
