Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：柠檬苦素由于其多种生物学效应而受到了广泛关注，椎间盘退变(IDD)也受到关注,因为该疾病的高患病率。在这项研究中,我们确定了柠檬苦素对IDD的影响以及潜在的作用机制，以寻找治疗IDD的新方法。
方法：建立IL-1β诱导的细胞炎症模型和诱导IDD的腰椎不稳定模型，以评估有或没有柠檬苦素治疗的IDD进展。我们进一步评估了MAPK/NF-κB和坏死途径以及椎间盘内特异性细胞外基质的改变。
结果：柠檬苦素通过减少促炎标志物如iNOS和COX-2的产生在体外抑制髓核内的炎症。柠檬苦素降低了NP细胞中MAPK/NF-κB信号通路和RIP1/RIP3/MLKL坏死通路的激活。此外，在腰椎不稳定模型中，柠檬苦素延迟IDD进展。
结论：柠檬苦素可能通过抑制NP细胞凋亡和调节椎间盘周围基质蛋白而延缓IDD，是IDD患者治疗的潜在药理研究方向。
方法：建立IL-1β诱导的细胞炎症模型和诱导IDD的腰椎不稳定模型，以评估有或没有柠檬苦素治疗的IDD进展。我们进一步评估了MAPK/NF-κB和坏死途径以及椎间盘内特异性细胞外基质的改变。
结果：柠檬苦素通过减少促炎标志物如iNOS和COX-2的产生在体外抑制髓核内的炎症。柠檬苦素降低了NP细胞中MAPK/NF-κB信号通路和RIP1/RIP3/MLKL坏死通路的激活。此外，在腰椎不稳定模型中，柠檬苦素延迟IDD进展。
结论：柠檬苦素可能通过抑制NP细胞凋亡和调节椎间盘周围基质蛋白而延缓IDD，是IDD患者治疗的潜在药理研究方向。
