He Yu, Junsheng Lou, Libin Ni, Minwei Yan, Kewu Zhu, Su Mao, Jungao Zhu
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引用次数: 0
摘要
骨关节炎(OA)是一种以细胞外基质(ECM)降解和炎症为特征的进行性关节疾病,与受损软骨细胞诱发的病理微环境改变有关。然而,目前的疗法并不能有效缓解 OA 的恶化。异槲皮素是一种天然黄酮苷化合物,具有抗癌、抗糖尿病和调节血脂等多种药理作用。以往的证据表明,异槲皮素在多种疾病中具有抗炎作用,但其对 OA 的影响尚未得到研究。本研究通过Western bolt、qRT-PCR和ELISA检测发现,异槲皮素可降低IL-1β诱导的ADAMTS5、MMP13、COX-2、iNOS和IL-6的升高,提示异槲皮素可抑制软骨细胞的炎症和ECM降解。通过核浆分离技术、Western 印迹和免疫细胞化学分析发现,Nrf2 和 NF-κB 通路在这一过程中被激活,异槲皮素可能依赖这一过程发挥其保护作用。在体内,X射线和SO染色结果表明,在小鼠OA模型中,关节内注射异槲皮素可减少软骨的降解。总之,本研究表明,异槲皮素可通过调节Nrf2/NF-κB信号轴而有益于软骨细胞,这支持了异槲皮素作为治疗OA的潜在药物。
Isoquercetin Ameliorates Osteoarthritis via Nrf2/NF-κB Axis: An In Vitro and In Vivo Study
Osteoarthritis (OA) is a progressive joint disease characterized by extracellular matrix (ECM) degradation and inflammation, which is involved with pathological microenvironmental alterations induced by damaged chondrocytes. However, current therapies are not effective in alleviating the progression of OA. Isoquercetin is a natural flavonoid glycoside compound that has various pharmacological effects including anticancer, anti-diabetes and blood lipid regulation. Previous evidence suggests that isoquercetin has anti-inflammatory properties in various diseases, but its effect on OA has not been investigated yet. In this study, through western bolt, qRT-PCR and ELISA, it was found that isoquercetin could reduce the increase of ADAMTS5, MMP13, COX-2, iNOS and IL-6 induced by IL-1β, suggesting that isoquercetin could inhibit the inflammation and ECM degradation of chondrocytes. Through nuclear-plasma separation technique, western blot and immunocytochemistry, it can be found that Nrf2 and NF-κB pathways are activated in this process, and isoquercetin may rely on this process to play its protective role. In vivo, the results of X-ray and SO staining show that intra-articular injection of isoquercetin reduces the degradation of cartilage in the mouse OA model. In conclusion, the present work suggests that isoquercetin may benefit chondrocytes by regulating the Nrf2/NF-κB signaling axis, which supports isoquercetin as a potential drug for the treatment of OA.
期刊介绍:
Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.