Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, PR China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, PR China; The Second School of Medicine of Wenzhou Medical University, Wenzhou 325000, PR China.
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, PR China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou 325000, PR China; The Second School of Medicine of Wenzhou Medical University, Wenzhou 325000, PR China.
Phytomedicine. 2024 Dec;135:156115. doi: 10.1016/j.phymed.2024.156115. Epub 2024 Sep 30.
Osteoarthritis (OA) is a progressive joint condition marked by the slow degradation of articular cartilage. Vinpocetine (Vin), a synthetic derivative of vincamine derived from the vinca plant, exhibits anti-inflammatory and antioxidant properties. Nevertheless, the specific role and mechanism of Vin in the treatment of OA remain largely unexplored.
The study is designed to uncover the impacts of Vin on tert‑butyl hydroperoxide (TBHP)-induced ferroptosis and to explore its potential role and underlying mechanisms in the treatment of OA. Concurrently, we established an OA mouse model through medial meniscal instability surgery to assess the therapeutic effects of Vin in vivo.
Through network pharmacology analysis, we have identified the key targets and potential pathways of Vin. To simulate an oxidative stress-induced OA environment in vitro, we induced chondrocyte injury using TBHP. We tested how Vin affects chondrocytes under TBHP induction by DHE and DCFH-DA probes, BODIPY-C11 and FerroOrange staining, mitochondrial function assessment, Western blotting, co-immunoprecipitation, and immunofluorescence techniques. Simultaneously, we established an OA mouse model through medial meniscal instability surgery to assess the in vivo therapeutic effects of Vin. In this model, we used X-ray and micro-CT imaging, SO staining, TB staining, H&E staining, and immunohistochemistry to analyze the role of Vin in detail.
This study demonstrated that Vin effectively suppressed TBHP-induced ferroptosis and extracellular matrix (ECM) degradation and significantly lessened mitochondrial damage associated with ferroptosis. In the OA mouse model, Vin improved cartilage degeneration, subchondral remodeling, synovitis, and ECM degradation. Vin worked by activating the Nrf2/GPX4 pathway and inhibiting the Keap1-Nrf2 interaction. This study focused on the function of ferroptosis in OA and its influence on chondrocyte damage and disease progression, offering novel perspectives on potential treatments.
Vin activated the Nrf2/GPX4 pathway, thereby slowing OA progression, inhibiting ferroptosis, and preventing ECM degradation.
骨关节炎（OA）是一种渐进性关节疾病，其特征是关节软骨的缓慢降解。长春西汀（Vin）是长春花植物中提取的长春胺的合成衍生物，具有抗炎和抗氧化作用。然而，Vin 治疗 OA 的具体作用和机制在很大程度上仍未得到探索。
本研究旨在揭示 Vin 对叔丁基过氧化物（TBHP）诱导的铁死亡的影响，并探讨其在 OA 治疗中的潜在作用和机制。同时，我们通过内侧半月板不稳定手术建立了 OA 小鼠模型，以评估 Vin 的体内治疗效果。
通过网络药理学分析，我们确定了 Vin 的关键靶点和潜在途径。为了在体外模拟氧化应激诱导的 OA 环境，我们使用 TBHP 诱导软骨细胞损伤。我们使用 DHE 和 DCFH-DA 探针、BODIPY-C11 和 FerroOrange 染色、线粒体功能评估、Western blot、免疫共沉淀和免疫荧光技术检测 Vin 在 TBHP 诱导下对软骨细胞的影响。同时，我们通过内侧半月板不稳定手术建立了 OA 小鼠模型，以评估 Vin 的体内治疗效果。在该模型中，我们使用 X 射线和微 CT 成像、SO 染色、TB 染色、H&E 染色和免疫组化技术详细分析 Vin 的作用。
本研究表明，Vin 可有效抑制 TBHP 诱导的铁死亡和细胞外基质（ECM）降解，并显著减轻与铁死亡相关的线粒体损伤。在 OA 小鼠模型中，Vin 改善了软骨退变、软骨下骨重塑、滑膜炎和 ECM 降解。Vin 通过激活 Nrf2/GPX4 通路和抑制 Keap1-Nrf2 相互作用发挥作用。本研究关注了铁死亡在 OA 中的功能及其对软骨细胞损伤和疾病进展的影响，为潜在治疗方法提供了新的视角。
Vin 通过激活 Nrf2/GPX4 通路减缓 OA 进展，抑制铁死亡和 ECM 降解。
