Trauma Center, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China (mainland).
Department of Orthopedic Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China (mainland).
Med Sci Monit. 2019 Sep 5;25:6649-6659. doi: 10.12659/MSM.916209.
BACKGROUND Chondrocyte dysfunction and apoptosis are 2 major features during the progression of osteoarthritis. Catalpol, an iridoid glycoside isolated from the root of Rehmannia, is a valuable medication with anti-inflammatory, anti-oxidative, and anti-apoptotic effects in various diseases. However, whether catalpol protects against osteoarthritis has not been investigated. MATERIAL AND METHODS To assess the role of catalpol in osteoarthritis and the potential mechanism of action, chondrocytes were treated with interleukin (IL)-1ß and various concentrations of catalpol. Catabolic metabolism, apoptotic level and relative signaling pathway were measured by western blot, real-time polymerase chain reaction and immunofluorescence staining. Meanwhile, we assess the cartilage degeneration in an experimental rat model using Safranin O fast green staining and cartilage was graded according to the Osteoarthritis Research Society International (OARSI) system. RESULTS The results showed that catalpol prevented chondrocyte apoptotic level triggered by IL-1ß, suppressed the release of catabolic enzymes, and inhibited the degradation of extracellular matrix induced by IL-1ß. Catalpol also inhibited the nuclear factor kappa B (NF-kappaB) pathway, reduced the production of inflammatory cytokines (IL-6, tumor necrosis factor-alpha) in IL-1ß-treated chondrocytes, and partially reversed cartilage degeneration in the knee joint in animal model of osteoarthritis. CONCLUSIONS Our work suggested that catalpol treatment attenuates IL-1ß-induced inflammatory response and catabolism in rat chondrocytes by inhibiting the NF-kappaB pathway, suggesting the therapeutic potential of catalpol for the treatment of osteoarthritis.
软骨细胞功能障碍和凋亡是骨关节炎进展过程中的两个主要特征。梓醇是从地黄根中分离得到的环烯醚萜苷，具有抗炎、抗氧化和抗凋亡作用，在多种疾病中具有重要的应用价值。然而，梓醇是否对骨关节炎具有保护作用尚未得到研究。
为了评估梓醇在骨关节炎中的作用及其潜在的作用机制，用白细胞介素（IL）-1β和不同浓度的梓醇处理软骨细胞。采用 Western blot、实时聚合酶链反应和免疫荧光染色法检测分解代谢、凋亡水平和相关信号通路。同时，我们采用番红 O 快绿染色法评估实验性大鼠模型中的软骨退变，并根据骨关节炎研究协会国际（OARSI）系统对软骨进行分级。
结果表明，梓醇可防止 IL-1β诱导的软骨细胞凋亡水平，抑制分解代谢酶的释放，并抑制 IL-1β诱导的细胞外基质降解。梓醇还抑制核因子 kappa B（NF-κB）通路，减少 IL-1β处理的软骨细胞中炎症细胞因子（IL-6、肿瘤坏死因子-α）的产生，并在骨关节炎动物模型中部分逆转膝关节软骨退变。
我们的工作表明，梓醇通过抑制 NF-κB 通路减轻 IL-1β诱导的大鼠软骨细胞炎症反应和分解代谢，提示梓醇治疗骨关节炎的潜力。
