Department of Orthopaedics, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.
Bone Development and Metabolism Research Center, Taizhou Hospital of Zhejiang Province, Linhai, Zhejiang, China.
J Pharm Pharmacol. 2023 Apr 17;75(5):612-624. doi: 10.1093/jpp/rgac094.
Limonin has received significant attention due to its multiple biological effects, intervertebral disc degeneration (IDD) is also of interest due to the high prevalence of this disease. In this study, we determined the effects of limonin on IDD and the underlying mechanism of action to find novel ways to treat IDD.
An IL-1β-induced cell inflammation model and a lumbar instability model inducing IDD were established to assess the progression of IDD with or without limonin treatment. We further evaluated MAPK/NF-κB and necroptosis pathways and alterations in the extracellular matrix specific within the disc.
Limonin suppresses inflammation in the nucleus pulposus in vitro by reducing the production of pro-inflammatory markers such as iNOS and COX-2. Limonin reduced the activation of the MAPK/NF-κB signalling pathway and the RIP1/RIP3/MLKL necroptosis pathway in the NP cells. Moreover, limonin delays the IDD progression in the lumbar instability model.
Limonin could potentially delay IDD by inhibiting NP cell necroptosis and modulating peripheral matrix proteins within the intervertebral disc and is a potential pharmacological research direction for the therapy in patients with IDD.
由于具有多种生物学效应，柠烯受到了广泛关注，椎间盘退变（IDD）也因其高发病率而受到关注。在这项研究中，我们确定了柠烯对 IDD 的作用及其作用机制，以期找到治疗 IDD 的新方法。
建立了 IL-1β诱导的细胞炎症模型和诱导 IDD 的腰椎不稳模型，以评估有或没有柠烯治疗时 IDD 的进展情况。我们进一步评估了 MAPK/NF-κB 和坏死性凋亡途径以及椎间盘内细胞外基质的变化。
柠烯通过减少促炎标志物（如 iNOS 和 COX-2）的产生，抑制体外核髓核中的炎症。柠烯降低了 NP 细胞中 MAPK/NF-κB 信号通路和 RIP1/RIP3/MLKL 坏死性凋亡通路的激活。此外，柠烯延迟了腰椎不稳模型中 IDD 的进展。
柠烯可能通过抑制 NP 细胞坏死性凋亡和调节椎间盘内的外周基质蛋白来延迟 IDD，这是 IDD 患者治疗的潜在药理学研究方向。
