Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China.
Food Funct. 2019 Sep 1;10(9):5873-5885. doi: 10.1039/c9fo00742c. Epub 2019 Aug 29.
Osteoarthritis (OA) is the most prevalent form of human arthritis which is characterized by the degradation of cartilage and inflammation. As a rare Sirt6 activator, cyanidin is the major component of anthocyanins commonly found in the Mediterranean diet, and increasing evidence has shown that cyanidin exhibits anti-inflammatory effects in a variety of diseases. However, the anti-inflammatory effects of cyanidin on OA have not been reported. In the present study, we identified that cyanidin treatment could strongly suppress the expression of NO, PGE2, TNF-α, IL-6, iNOs, COX-2, ADAMTS5 and MMP13, and reduce the degradation of aggrecan and collagen II in IL-1β-induced human OA chondrocytes, indicating the anti-inflammatory effect of cyanidin. Further investigation of the mechanism involved revealed that cyanidin could upregulate the Sirt6 level in a dose-dependent manner and Sirt6 silencing abolished the effect of cyanidin in IL-1β-stimulated human OA chondrocytes, indicating a stimulatory effect of cyanidin on Sirt6 activation. Meanwhile, we found that cyanidin could inhibit the NF-κB pathway in IL-1β-stimulated human OA chondrocytes and its effect may to some extent depend on Sirt6 activation, suggesting that cyanidin may exert a protective effect through regulating the Sirt6/NF-κB signaling axis. Moreover, the in vivo study also proved that cyanidin ameliorated the development of OA in surgical destabilization of the medial meniscus (DMM) mouse OA models. In conclusion, these results demonstrate that cyanidin may have therapeutic potential for the treatment of OA.
骨关节炎（OA）是最常见的人类关节炎形式，其特征是软骨降解和炎症。作为一种罕见的 Sirt6 激活剂，矢车菊素是在地中海饮食中常见的花色苷的主要成分，越来越多的证据表明，矢车菊素在多种疾病中具有抗炎作用。然而，矢车菊素对 OA 的抗炎作用尚未报道。在本研究中，我们确定矢车菊素处理可以强烈抑制 NO、PGE2、TNF-α、IL-6、iNOS、COX-2、ADAMTS5 和 MMP13 的表达，并减少 IL-1β诱导的人 OA 软骨细胞中聚集蛋白聚糖和胶原 II 的降解，表明矢车菊素具有抗炎作用。对涉及的机制的进一步研究表明，矢车菊素可以以剂量依赖的方式上调 Sirt6 水平，而 Sirt6 沉默则消除了矢车菊素在 IL-1β刺激的人 OA 软骨细胞中的作用，表明矢车菊素对 Sirt6 激活具有刺激作用。同时，我们发现矢车菊素可以抑制 IL-1β刺激的人 OA 软骨细胞中的 NF-κB 途径，其作用在某种程度上可能依赖于 Sirt6 激活，表明矢车菊素可能通过调节 Sirt6/NF-κB 信号轴发挥保护作用。此外，体内研究也证明了矢车菊素可以改善内侧半月板手术不稳定（DMM）小鼠 OA 模型中 OA 的发展。总之，这些结果表明矢车菊素可能具有治疗 OA 的潜力。
