Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway
Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway
复制标题
和厚朴酚通过抑制TXNIP-NLRP3炎症小体信号通路的激活减轻椎间盘退变
DOI：
10.1016/j.freeradbiomed.2018.04.008
复制
发表时间：
2018-05-20
影响因子：
7.4
通讯作者：
Hu, Zhi-Jun
中科院分区：
文献类型：
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作者：
Tang, Pan;Gu, Jia-Ming;Hu, Zhi-Jun
椎间盘退变 (IVDD) 是一种多因素疾病，导致许多脊柱相关疾病，导致全世界劳动力残疾和沉重的社会成本。和厚朴酚是一种低分子量天然产物，可以渗透并分布在 IVD 中，在大鼠尾模型中达到治疗效果。因此，本研究旨在利用髓核细胞检测和厚朴酚的抗炎、抗氧化和体外诊断（IVD）保护作用，并探讨其机制，为今后临床治疗体外诊断（IVDD）提供新的基础。在当前的研究中，我们证明和厚朴酚可抑制 H2O2 诱导的细胞凋亡（caspase-9、caspase-3 和 bax）、氧化应激介质（ROS、MDA）的水平、炎症介质（Interleukin-6、COX-2 和 iNOS）的表达、主要基质降解蛋白酶（MMP-3、MMP-13、ADAMTS5 和 ADAMTS4) 与髓核降解相关。此外，我们发现和厚朴酚通过上调髓核中的 II 型胶原 (Col II) 和 SOX9 等细胞外基质合成代谢因子来保护髓核。我们还发现和厚朴酚抑制 H2O2 刺激的髓核细胞中 NFkB 和 JNK 的磷酸化以及 TXNIP-NLRP3 炎症小体的激活，从而抑制下游炎症介质（如 Interleukin-1 beta）的激活。此外，和厚朴酚在穿刺诱导的大鼠模型中的 IVDD 进展中显示出软骨保护作用。因此，我们的结果表明和厚朴酚通过抑制 TXNIP/NLRP3/caspase-1/Interleukin-1 beta 信号轴以及激活 NF-kB 和 JNK 来抑制 H2O2 诱导的细胞凋亡、氧化应激和炎症反应。和厚朴酚具有髓核保护特性，可能有助于抑制 IVDD 的发病机制。
Intervertebral disc degeneration (IVDD) is a multifactorial disease and responsible for many spine related disorders, causes disability in the workforce and heavy social costs all over the world. Honokiol, a low molecular weight natural product, could penetrate into and distribute in IVDs to achieve therapeutic effect in a rat tail model. Therefore, the present study was undertaken to examine the antiinflammatory, antioxidation and IVD-protective effect of honokiol using nucleus pulposus cells and investigate its mechanisms to provide a new basis for future clinical treatment of IVDD. In the current study, we demonstrated that honokiol inhibits the H2O2-induced apoptosis (caspase-9, caspase-3, and bax), levels of oxidative stress mediators (ROS, MDA), expression of inflammatory mediators (Interleukin-6, COX-2, and iNOS), major matrix degrading proteases (MMP-3, MMP-13, ADAMTS5, and ADAMTS4) associated with nucleus pulposus degradation. Furthermore, we found nucleus pulposus protective ability of honokiol by up-regulating extra cellular matrix anabolic factors like type II collagen (Col II) and SOX9 in nucleus pulposus. We also found that honokiol suppressed the phosphorylation of NFkB and JNK, and activation of TXNIP-NLRP3 inflammasome in H2O2-stimulated nucleus pulposus cells, thereby inhibiting the activation of downstream inflammatory mediators such as Interleukin-1 beta. Furthermore, honokiol showed a cartilage protective effect in the progression of IVDD in a rat model induced by puncture. Thus, our results demonstrate that honokiol inhibited the H2O2 induced apoptosis, oxidative stress, and inflammatory responses through the depression of TXNIP/NLRP3/caspase-1/ Interleukin - 1 beta signaling axis and the activation of NF-kB and JNK. Honokiol possess nucleus pulposus protective properties and may be of value in suppressing the pathogenesis of IVDD.