Osteoarthritis is one of the common diseases that seriously affects the quality of life of middle‐aged and elderly people worldwide. Geniposidic acid (GPA) is extracted from Eucommia ulmoides that exhibits various pharmacological effects. This study investigated the function of GPA on osteoarthritis (OA) in IL‐1β‐stimulated mouse chondrocytes and mouse OA model. Mouse OA model was established by destabilization of the medial meniscus (DMM) and GPA was given intraperitoneal injection. The results demonstrated that GPA could alleviate DMM‐induced OA in mice. In vitro, IL‐1β‐induced PGE2, NO, MMP1 and MMP3 were suppressed by GPA. Furthermore, IL‐1β‐induced ferroptosis was inhibited by GPA, as confirmed by the inhibition of MDA, iron, and ROS, as well as the upregulation of GSH, GPX4, and Ferritin. In addition, GPA was found to increase the expression of Nrf2 and HO‐1. And the inhibition of GPA on IL‐1β‐induced inflammation and ferroptosis were prevented by Nrf2 inhibitor. In conclusion, GPA alleviates OA progression through inhibiting inflammation and chondrocytes ferroptosis via Nrf2 signalling pathway.

中文翻译：

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京尼平苷酸通过抑制炎症和软骨细胞铁死亡来缓解骨关节炎的进展

骨关节炎是严重影响全球中老年人生活质量的常见疾病之一。京尼平苷酸 (GPA) 是从杜仲表现出多种药理作用。本研究在 IL-1β 刺激的小鼠软骨细胞和小鼠 OA 模型中研究了 GPA 对骨关节炎 (OA) 的作用。通过内侧半月板(DMM)失稳建立小鼠OA模型，腹腔注射GPA。结果表明，GPA 可以减轻 DMM 诱导的小鼠 OA。在体外，GPA 抑制 IL-1β 诱导的 PGE2、NO、MMP1 和 MMP3。此外，IL-1β诱导的铁死亡受到GPA的抑制，通过抑制MDA、铁和ROS以及上调GSH、GPX4和铁蛋白证实了这一点。此外，GPA 还被发现可以增加 Nrf2 和 HO-1 的表达。 Nrf2 抑制剂可以阻止 GPA 对 IL-1β 诱导的炎症和铁死亡的抑制。总之，GPA 通过 Nrf2 信号通路抑制炎症和软骨细胞铁死亡，从而缓解 OA 进展。