Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1837-1845. doi: 10.3892/mmr.2017.6771. Epub 2017 Jun 14.
Curcumin possesses strong anti-inflammatory, anti-rheumatoid and anti-oxidative activities, and has the potential to inhibit nuclear factor‑κB (NF‑κB) signaling. Cartilage damage in osteoarthritis (OA) is largely mediated by interleukin-1β (IL-1β) via activation of various transcription factors, including NF‑κB and activator protein‑1. The aim of the present study was to determine whether IL‑1β induces matrix metalloproteinase-13 (MMP-13) expression and inhibits type II collagen expression, as well as to examine whether cell proliferation may be inhibited by curcumin through the inhibition of NF‑κB signaling. The effects of curcumin were investigated in rat articular chondrocyte cell cultures treated with IL‑1β in the presence or absence of curcumin or the NF‑κB inhibitor pyrrolidine dithiocarbamate. Western blotting and reverse transcription‑quantitative polymerase chain reaction were conducted to evaluate protein and mRNA expression levels of type II collagen, MMP‑13, NF‑κB inhibitor α (IκBα), phosphorylated‑IκBα and NF‑κB subunit p65/RelA. Western blotting and immunofluorescence were performed to examine the effects of curcumin on the expression, phosphorylation and nuclear translocation of NF‑κB‑associated proteins. The effects of curcumin on cell proliferation were evaluated by Cell Counting Kit‑8 (CCK‑8). Curcumin was demonstrated to inhibit the IL‑1β‑induced activation of NF‑κB by suppressing IκBα phosphorylation and p65/RelA nuclear translocation. These events were associated with the downregulation of MMP‑13 expression and the upregulation of type II collagen expression, both of which are considered to be NF‑κB targets. CCK‑8 assays revealed that co‑treatment with curcumin resulted in increased proliferation in IL‑1β‑treated chondrocytes. These findings implicated curcumin as a naturally occurring anti‑inflammatory agent for the treatment of OA via inhibition of NF‑κB signaling.
姜黄素具有很强的抗炎、抗风湿和抗氧化活性，并且有可能抑制核因子-κB（NF-κB）信号通路。骨关节炎（OA）中的软骨损伤主要是通过白细胞介素-1β（IL-1β）通过激活各种转录因子，包括 NF-κB 和激活蛋白-1 来介导的。本研究旨在确定 IL-1β 是否诱导基质金属蛋白酶-13（MMP-13）表达并抑制 II 型胶原表达，以及通过抑制 NF-κB 信号通路是否可以抑制细胞增殖。在存在或不存在姜黄素或 NF-κB 抑制剂吡咯烷二硫代氨基甲酸盐的情况下，用 IL-1β 处理大鼠关节软骨细胞培养物，研究姜黄素的作用。通过 Western blot 和逆转录-定量聚合酶链反应评估 II 型胶原、MMP-13、NF-κB 抑制剂α（IκBα）、磷酸化-IκBα 和 NF-κB 亚基 p65/RelA 的蛋白和 mRNA 表达水平。通过 Western blot 和免疫荧光法检查姜黄素对 NF-κB 相关蛋白表达、磷酸化和核转位的影响。通过细胞计数试剂盒-8（CCK-8）评估姜黄素对细胞增殖的影响。姜黄素通过抑制 IκBα 磷酸化和 p65/RelA 核易位来抑制 IL-1β 诱导的 NF-κB 激活。这些事件与 MMP-13 表达下调和 II 型胶原表达上调有关，这两者均被认为是 NF-κB 的靶标。CCK-8 测定表明，与姜黄素共同处理可导致 IL-1β 处理的软骨细胞增殖增加。这些发现表明姜黄素通过抑制 NF-κB 信号通路成为治疗 OA 的天然抗炎剂。
