Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Biomed Pharmacother. 2018 May;101:745-753. doi: 10.1016/j.biopha.2018.01.100. Epub 2018 Mar 22.
Most low back pain is caused by intervertebral discs (IVD) degeneration, a disease that prevalence is increasing with age. Halofuginone, an analog of ferbrifugine isolated from plant Dichroa febrifuga, has drawn much attention in recent years for the wide range of bioactivities in malaria, cancer, fibrotic and autoimmune diseases. In this study, we evaluated the benefit effects of halofuginone in IVD degeneration treatment in a validated rabbit puncture model. Halofuginone treatment could attenuate disc degeneration by suppressing the decrease of discs height and nucleus pulposus signal strength. Besides, halofuginone treatment could suppress mRNA and protein expression of collagen I in nucleus pulposus. This might possibly due to the inactivation of transform growth factor-β (TGFβ) signal pathway by down-regulating p-Samd3 and up-regulating inhibitory Smad7. Then, we evaluated the effects of halofuginone treatment on nuclear factor of kappa B (NF-κB) signal pathway and its downstream pro-inflammatory cytokines. The level of p-p65 and p-IκBα was down-regulated in halofuginone treated group, indicating the inactivation of NF-κB signal pathway. The mRNA expression of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and interleukin 8 (IL-8) was decreased in nucleus pulposus too, indicating the down-regulation of pro-inflammatory cytokines. In conclusion, halofuginone treatment could attenuate IVD degeneration and this was possibly due to suppressing of collagen I production and inactivation of TGFβ and NF-κB signal pathway in nucleus pulposus of degenerated discs. These results suggest that halofuginone has the potential for IVD degeneration treatment, but more research is needed to validate this.
大多数下腰痛是由椎间盘（IVD）退变引起的，这种疾病的患病率随着年龄的增长而增加。哈尔福林酮是一种从植物中华千金藤中分离得到的法呢基菲咯嗪类似物，近年来因其在疟疾、癌症、纤维化和自身免疫性疾病中的广泛生物活性而备受关注。在这项研究中，我们在经过验证的兔穿刺模型中评估了哈尔福林酮在治疗 IVD 退变中的有益作用。哈尔福林酮治疗可通过抑制椎间盘高度和髓核信号强度的降低来减轻椎间盘退变。此外，哈尔福林酮治疗可抑制髓核中胶原 I 的 mRNA 和蛋白表达。这可能是由于通过下调 p-Samd3 和上调抑制性 Smad7 来抑制转化生长因子-β（TGFβ）信号通路的失活。然后，我们评估了哈尔福林酮治疗对核因子-κB（NF-κB）信号通路及其下游促炎细胞因子的影响。在哈尔福林酮治疗组中，p-p65 和 p-IκBα 的水平下调，表明 NF-κB 信号通路失活。髓核中白细胞介素 1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素 6（IL-6）和白细胞介素 8（IL-8）的 mRNA 表达也降低，表明促炎细胞因子的下调。总之，哈尔福林酮治疗可减轻 IVD 退变，这可能是由于抑制退变椎间盘髓核中胶原 I 的产生以及 TGFβ 和 NF-κB 信号通路的失活。这些结果表明哈尔福林酮具有治疗 IVD 退变的潜力，但需要进一步研究来验证这一点。
