Liu Changchang, Duan Guangyu, Xu Shengjie, Li Teng, Sun Xin
Nanjing Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu Province, China.
Heliyon. 2024 Nov 15;10(23):e40458. doi: 10.1016/j.heliyon.2024.e40458. eCollection 2024 Dec 15.
Osteoarthritis (OA) is a prevalent musculoskeletal disorder globally. This study explored the therapeutic potential of Epimedin C (Epi C) in OA and its mechanisms. We isolated primary chondrocytes from mice and induced inflammatory damage using interleukin-1β (IL-1β) to evaluate Epi C's capacity to preserve cell viability and inhibit apoptosis, employing cell counting kit (CCK8) assays, EdU staining, and flow cytometry. Additionally, its anti-inflammatory effects were quantified using enzyme-linked immunosorbent assay (ELISA), Western blot, and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), alongside assessments of extracellular matrix (ECM) degradation. , OA was induced in mice through destabilization of the medial meniscus (DMM), followed by Epi C administration. Cartilage integrity was evaluated via micro-computed tomography (CT) and histology. Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway involvement was investigated through siRNA knockdown and oxidative stress markers, while NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome expression was measured to establish Epi C's modulatory effect. Our study revealed that Epi C protected against IL-1β-induced chondrocyte damage by enhancing cell viability, reducing apoptosis, and dampening inflammatory responses. The studies demonstrated Epi C's role in preserving cartilage structure, activating nuclear factor erythroid 2-related factor 2 (Nrf2), and inhibiting NLRP3 expression in DMM-induced OA mice. Conclusively, our findings provide substantial evidence of Epi C's therapeutic efficacy in OA, primarily through its modulation of the Nrf2-mediated NLRP3 inflammasome pathway, offering novel insights into its management role in OA.
骨关节炎（OA）是全球一种普遍存在的肌肉骨骼疾病。本研究探讨了朝藿定C（Epi C）在OA中的治疗潜力及其作用机制。我们从小鼠中分离出原代软骨细胞，并用白细胞介素-1β（IL-1β）诱导炎症损伤，采用细胞计数试剂盒（CCK8）检测、EdU染色和流式细胞术来评估Epi C维持细胞活力和抑制细胞凋亡的能力。此外，使用酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法和实时荧光定量聚合酶链反应（RT-qPCR）对其抗炎作用进行定量，并评估细胞外基质（ECM）降解情况。通过内侧半月板不稳定（DMM）诱导小鼠发生OA，随后给予Epi C。通过微型计算机断层扫描（CT）和组织学评估软骨完整性。通过小干扰RNA（siRNA）敲低和氧化应激标志物研究核因子红细胞2相关因子2（Nrf2）通路的参与情况，同时检测NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎性小体的表达，以确定Epi C的调节作用。我们的研究表明，Epi C通过增强细胞活力、减少细胞凋亡和减轻炎症反应，保护软骨细胞免受IL-1β诱导的损伤。这些研究证明了Epi C在DMM诱导的OA小鼠中对维持软骨结构、激活核因子红细胞2相关因子2（Nrf2）和抑制NLRP3表达的作用。总之，我们的研究结果为Epi C在OA中的治疗效果提供了大量证据，主要是通过其对Nrf2介导的NLRP3炎性小体通路的调节，为其在OA中的管理作用提供了新的见解。
