桑辛素通过 NF-κB 信号通路改善 IL-1β 诱导的软骨细胞炎症和骨关节炎。
Morusin Ameliorates IL-1β-Induced Chondrocyte Inflammation and Osteoarthritis via NF-κB Signal Pathway.
机构信息
Department of Orthopaedics, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, People's Republic of China.
The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People's Republic of China.
出版信息
Drug Des Devel Ther. 2020 Mar 26;14:1227-1240. doi: 10.2147/DDDT.S244462. eCollection 2020.
PURPOSE
Osteoarthritis (OA) is one of the most common degenerative joint diseases in the world, characterized primarily by the progressive degradation of articular cartilage. Accumulating evidence has shown that Morusin, a flavonoid derived from the root bark of (mulberry) plants, exerts unique protective properties in several diseases. However, its effects on OA, specifically, have not yet been characterized.
METHODS
In this study, we evaluated the anti-inflammatory effect of Morusin on mouse chondrocytes and its underlying mechanism in vitro. In addition, the protective effect of Morusin on destabilization of the medial meniscus (DMM) model was also explored in vivo.
RESULTS
In vitro, IL-1β-induced activation of inflammatory factors (TNF-α, IL-6, INOS and COX2) was dramatically suppressed by Morusin. Further, Morusin treatment inhibited the expression of ADAMTS5 and metalloproteinase (MMPs), both of which regulate extracellular matrix degradation. Morusin also decreased IL-1β-induced p65 phosphorylation and IκBα degradation. In vivo, degradation of the articular cartilage following surgical DMM, which mimicked OA pathology, was abrogated following treatment with Morusin, thus demonstrating a protective effect in the DMM model.
CONCLUSION
Herein, we demonstrate that Morusin reduces the OA inflammatory response in vitro and protects against articular cartilage degradation in vivo potentially via regulation of the NF-κB pathway. Hence, Morusin may prove to be an effective candidate for novel OA therapeutic strategies.
目的
骨关节炎(OA)是世界上最常见的退行性关节疾病之一,主要特征为关节软骨进行性退化。越来越多的证据表明,桑辛,一种从桑科植物根皮中提取的类黄酮,在几种疾病中具有独特的保护特性。然而,它对 OA 的影响,特别是,尚未得到描述。
方法
在这项研究中,我们评估了 Morusin 对小鼠软骨细胞的抗炎作用及其在体外的潜在机制。此外,还探讨了 Morusin 对内侧半月板不稳定(DMM)模型的保护作用。
结果
体外,Morusin 显著抑制了 IL-1β 诱导的炎症因子(TNF-α、IL-6、INOS 和 COX2)的激活。此外,Morusin 处理抑制了 ADAMTS5 和金属蛋白酶(MMPs)的表达,这两者都调节细胞外基质的降解。Morusin 还降低了 IL-1β 诱导的 p65 磷酸化和 IκBα 降解。体内,手术后 DMM 引起的软骨退化,模拟 OA 病理学,经 Morusin 治疗后得到了缓解,因此在 DMM 模型中显示出了保护作用。
结论
本研究表明,Morusin 减少了体外 OA 的炎症反应,并通过调节 NF-κB 通路保护体内的软骨降解。因此,Morusin 可能成为一种新的 OA 治疗策略的有效候选药物。