Purpose: Intervertebral disc degeneration (IDD) is one of the most prevalent musculoskeletal disorders. The nucleus pulposus is the major component of the intervertebral disc, and nucleus pulposus cells (NPCs) play a significant role in the normal functioning of the intervertebral disc. Reactive oxygen species (ROS) generation, inflammation and extracellular matrix degradation in NPCs contribute to the degeneration of intervertebral discs. Acacetin is a drug that exerts antioxidant and anti-inflammatory effects on many types of cells. However, whether acacetin can relieve the degeneration of NPCs remains unknown.
Methods: NPCs were extracted from rat intervertebral discs. The NPCs were treated with tert-butyl peroxide (TBHP) to simulate a high-ROS environment, and acacetin was subsequently added. The contents of ROS, inflammatory mediators (COX-2, iNOS) and extracellular matrix components (aggrecan, collagen II, MMP13, MMP9, MMP3) were measured. Components of related signaling pathways (Nrf2, MAPK) were also evaluated. To determine the effect of acacetin in vivo, we simulated disc degeneration via needle puncture. Acacetin was then applied intraperitoneally, and the degenerative status was evaluated using MRI and histopathological analysis.
Results: In vitro, acacetin alleviated TBHP-induced ROS generation and upregulated the expression of antioxidant proteins, including HO-1, NQO1, and SOD. In addition, acacetin relieved the TBHP-induced generation of inflammatory mediators (COX-2, iNOS) and degradation of the extracellular matrix (aggrecan, collagen II, MMP13, MMP9, and MMP3). Acacetin exerted its effect by activating the Nrf2 pathway and inhibiting p38, JNK and ERK1/2 phosphorylation. In vivo, acacetin ameliorated puncture-induced disc degeneration in a rat tail model, which was evaluated using MRI and histopathological analysis.
Conclusion: Acacetin alleviated IDD in vitro and in vivo and may have the potential to be developed as an effective treatment for IDD.

Keywords: acacetin, intervertebral disc degeneration, IDD, reactive oxygen species, ROS, inflammation


中文翻译：

---

金合欢素可减轻髓核细胞的炎症和基质降解，并改善体内椎间盘退变

目的：椎间盘退变（IDD）是最普遍的肌肉骨骼疾病之一。髓核是椎间盘的主要组成部分，髓核细胞在椎间盘的正常功能中发挥着重要作用。NPC 中的活性氧 (ROS) 生成、炎症和细胞外基质降解有助于椎间盘的退化。金合欢素是一种对多种细胞具有抗氧化和抗炎作用的药物。然而，金合欢素是否能缓解 NPC 的退化仍是未知数。
方法：从大鼠椎间盘中提取NPC。NPC 用过氧化叔丁基 (TBHP) 处理以模拟高活性氧环境，随后添加金合欢素。测定 ROS、炎症介质（COX-2、iNOS）和细胞外基质成分（聚集蛋白聚糖、胶原蛋白 II、MMP13、MMP9、MMP3）的含量。还评估了相关信号通路（Nrf2、MAPK）的成分。为了确定金合欢素在体内的作用，我们通过针刺模拟椎间盘退变。然后在腹膜内应用金合欢素，并使用 MRI 和组织病理学分析评估退行性状态。
结果：在体外，金合欢素可减轻 TBHP 诱导的 ROS 生成并上调抗氧化蛋白的表达，包括 HO-1、NQO1 和 SOD。此外，金合欢素可减轻 TBHP 诱导的炎症介质（COX-2、iNOS）的产生和细胞外基质（聚集蛋白聚糖、胶原蛋白 II、MMP13、MMP9 和 MMP3）的降解。Acacetin 通过激活 Nrf2 通路和抑制 p38、JNK 和 ERK1/2 磷酸化发挥其作用。在体内，金合欢素改善了大鼠尾巴模型中穿刺诱导的椎间盘退变，该模型使用 MRI 和组织病理学分析进行了评估。
结论：金合欢素在体外和体内均能缓解 IDD，有可能被开发为 IDD 的有效治疗方法。

关键词：金合欢素, 椎间盘退变, IDD, 活性氧, ROS, 炎症