Department of Orthopedics, Tianjin Hospital, Tianjin, 300211, China.
Department of Orthopedics, Tianjin Hospital, Tianjin, 300211, China.
Eur J Pharmacol. 2020 Sep 15;883:173341. doi: 10.1016/j.ejphar.2020.173341. Epub 2020 Jul 4.
Osteoarthritis (OA) is a common yet destructive disease affecting the articular cartilage, and is a major cause of immense suffering and disability for millions of people. Previous studies have shown that triptolide (TPL), an active compound derived from Tripterygium wilfordii, has potent immunosuppressive and anti-inflammatory activities useful for treating chronic diseases. However, whether TPL has immunosuppressive activity against OA is not known. In this study, we assessed the therapeutic effects of TPL on interleukin-1-beta (IL-1β)-induced OA in rats. Histological and protein analyses revealed that TPL not only could inhibit interleukin-6 (IL-6) and cyclooxygenase-2 (COX2) protein expression in cells and disrupt inflammation, but it also reduced the expression of matrix metalloproteinase (MMP)-3 and 13. Our results also supported the ability of TPL to suppress the osteoprotegerin/receptor activator of nuclear factor kappa-beta (NF-κB)/receptor activator of NF-κB ligand (OPG/RANK/RANKL) and NF-κB signaling pathways induced by IL-1β. Together these data suggest that TPL may be a potentially valuable treatment for OA, regulating associated inflammation and pain.
骨关节炎(OA)是一种常见但具有破坏性的疾病,影响关节软骨,是数百万人遭受巨大痛苦和残疾的主要原因。先前的研究表明,雷公藤红素(TPL),一种从雷公藤中提取的活性化合物,具有强大的免疫抑制和抗炎活性,可用于治疗慢性疾病。然而,TPL 是否对 OA 具有免疫抑制活性尚不清楚。在这项研究中,我们评估了 TPL 对白细胞介素-1β(IL-1β)诱导的大鼠 OA 的治疗作用。组织学和蛋白质分析表明,TPL 不仅可以抑制白细胞介素-6(IL-6)和环氧化酶-2(COX2)蛋白在细胞中的表达并破坏炎症,还可以降低基质金属蛋白酶(MMP)-3 和 13 的表达。我们的结果还支持 TPL 抑制核因子 kappa-B(NF-κB)/核因子κB 配体(RANKL)/核因子κB 受体激活剂(RANK)/骨保护素(OPG)信号通路的能力,该通路由 IL-1β 诱导。这些数据表明,TPL 可能是治疗 OA 的一种有价值的药物,可调节相关炎症和疼痛。