Department of Orthopedics, The First Hospital of Putian City, Putian, China.
Immun Inflamm Dis. 2023 May;11(5):e848. doi: 10.1002/iid3.848.
Osteoarthritis is a degenerative knee joint disease featured with articular cartilage degeneration and inflammation. Alisol A 24-acetate (ALA-24A) is an active triterpene that has antioxidant and anti-inflammatory pharmacological properties. However, its effect and molecular mechanism on osteoarthritis progression have not been reported.
IL-1β-induced chondrocyte injury model and monosodium iodoacetate (MIA)-induced rat osteoarthritis model were used. The protective effects of ALA-24A on osteoarthritis were evaluated by determining cell viability, extracellular matrix (ECM) degradation, inflammatory response and oxidative stress using CCK-8 assay, Western blot, ELISA, and DCFH-DA fluorescent probe. The severity and matrix degradation of articular cartilage were assessed by histopathological and immunohistochemical examination.
We found that ALA-24A attenuated IL-1β-induced cell viability inhibition Moreover, ALA-24A suppressed expression levels of ECM degradation-related genes ADAMTS5 and MMP13, and promoted expression levels of ECM synthesis-related genes Aggrecan and Collagen II. In addition, ALA-24A treatment decreased reactive oxygen species (ROS) production and increased antioxidant enzymes (SOD, CAT, and GSH-px) activities, while increased MDA levels. The inflammatory levels of NO, PGE2, TNF-α, and IL-6 were also reduced following treatment with ALA-24A. Our data also revealed that ALA-24A treatment triggered p-AMPK upregulation and p-mTOR downregulation. In rat osteoarthritis model, ALA-24A treatment significantly alleviated the severity and matrix degradation of articular cartilage comparted with model group.
Our findings suggested a protective role of ALA-24A against osteoarthritis by inhibiting ROS and inflammatory response. Furthermore, ALA-24A might be a promising therapeutic option for osteoarthritis treatment.
骨关节炎是一种退行性膝关节疾病，其特征为关节软骨退化和炎症。 24-乙酰泽泻醇 A（ALA-24A）是一种具有抗氧化和抗炎药理作用的活性三萜。然而，它对骨关节炎进展的影响及其分子机制尚未报道。
使用 IL-1β诱导的软骨细胞损伤模型和单碘乙酸（MIA）诱导的大鼠骨关节炎模型。通过 CCK-8 测定法、Western blot、ELISA 和 DCFH-DA 荧光探针测定细胞活力、细胞外基质（ECM）降解、炎症反应和氧化应激，评估 ALA-24A 对骨关节炎的保护作用。通过组织病理学和免疫组织化学检查评估关节软骨的严重程度和基质降解。
我们发现 ALA-24A 可减轻 IL-1β诱导的细胞活力抑制作用。此外，ALA-24A 抑制 ECM 降解相关基因 ADAMTS5 和 MMP13 的表达水平，并促进 ECM 合成相关基因 Aggrecan 和 Collagen II 的表达水平。此外，ALA-24A 治疗可降低活性氧（ROS）的产生并增加抗氧化酶（SOD、CAT 和 GSH-px）的活性，同时增加 MDA 水平。经 ALA-24A 处理后，NO、PGE2、TNF-α和 IL-6 的炎症水平也降低。我们的数据还表明，ALA-24A 处理可触发 p-AMPK 上调和 p-mTOR 下调。在大鼠骨关节炎模型中，与模型组相比，ALA-24A 治疗可显著减轻关节软骨的严重程度和基质降解。
我们的研究结果表明，ALA-24A 通过抑制 ROS 和炎症反应对骨关节炎具有保护作用。此外，ALA-24A 可能是治疗骨关节炎的一种有前途的治疗选择。
