Fang Xuan, Zhao Hongqi, Xu Tao, Wu Hua, Sheng Gaohong
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China.
Pharmaceuticals (Basel). 2024 Sep 26;17(10):1268. doi: 10.3390/ph17101268.
BACKGROUND/OBJECTIVES: Osteoarthritis (OA) is a prevalent degenerative disease globally, characterized by cartilage degradation and joint dysfunction. Current treatments are insufficient for halting OA progression. Irigenin (IRI), a flavonoid extracted from natural plants with anti-inflammatory and antioxidant properties, has demonstrated potential in mitigating inflammation and oxidative stress in various diseases; however, its effects on OA remain unexplored. This study aims to evaluate the therapeutic effects of IRI on OA through in vivo and in vitro experiments and to elucidate the underlying molecular mechanisms.
In vitro, chondrocytes were exposed to hydrogen peroxide (HO) to induce an oxidative stress environment and were then treated with IRI. Western blotting, RT-qPCR, immunofluorescence staining assays, flow cytometry, and apoptosis assays were employed to assess the effects of IRI on chondrocyte matrix homeostasis, inflammatory response, and apoptosis. In vivo, an OA rat model was treated with regular IRI injections, and therapeutic effects were evaluated using micro-CT, histological staining, and immunohistochemistry assays.
IRI treatment restored matrix homeostasis in chondrocytes and effectively suppressed HO-induced inflammation and apoptosis. Subsequent studies further revealed that IRI exerts its therapeutic effects by activating the Nrf2/HO-1 pathway. Inhibition of Nrf2 expression in chondrocytes partially blocked the anti-inflammatory and antioxidant effects of IRI. In the OA rat model, regular IRI injections effectively ameliorated cartilage degeneration.
This study identifies IRI as a promising strategy for OA treatment by modulating inflammation and apoptosis through the Nrf2/HO-1 pathway.
背景/目的：骨关节炎（OA）是一种在全球范围内普遍存在的退行性疾病，其特征为软骨降解和关节功能障碍。目前的治疗方法不足以阻止OA的进展。鸢尾黄素（IRI）是一种从天然植物中提取的具有抗炎和抗氧化特性的黄酮类化合物，已在多种疾病中显示出减轻炎症和氧化应激的潜力；然而，其对OA的影响仍未得到探索。本研究旨在通过体内和体外实验评估IRI对OA的治疗效果，并阐明其潜在的分子机制。
在体外，将软骨细胞暴露于过氧化氢（HO）以诱导氧化应激环境，然后用IRI处理。采用蛋白质免疫印迹法、逆转录-定量聚合酶链反应、免疫荧光染色分析、流式细胞术和凋亡分析来评估IRI对软骨细胞基质稳态、炎症反应和凋亡的影响。在体内，用常规IRI注射治疗OA大鼠模型，并使用微型计算机断层扫描、组织学染色和免疫组织化学分析来评估治疗效果。
IRI处理恢复了软骨细胞中的基质稳态，并有效抑制了HO诱导的炎症和凋亡。随后的研究进一步表明，IRI通过激活Nrf2/HO-1途径发挥其治疗作用。抑制软骨细胞中Nrf2的表达部分阻断了IRI的抗炎和抗氧化作用。在OA大鼠模型中，定期注射IRI有效改善了软骨退变。
本研究确定IRI是一种有前景的OA治疗策略，可通过Nrf2/HO-1途径调节炎症和凋亡。
