Ligustilide alleviated IL-1β induced apoptosis and extracellular matrix degradation of nucleus pulposus cells and attenuates intervertebral disc degeneration in vivo

• Published in: International immunopharmacology 2019-04, Vol.69, p.398-407
• Main Authors: Wang, Ke, Chen, Tingting, Ying, Xiaozhou, Zhang, Zengjie, Shao, Zhenxuan, Lin, Jialiang, Xu, Tianzhen, Chen, Yu, Wang, Xiangyang, Chen, Jiaoxiang, Sheng, Sunren
• Format: Article
• Language: English
• Subjects: Apoptosis; Cyclooxygenase-2; Cytokines; Degeneration; Degradation; ECM degradation; Extracellular matrix; IL-1β; Inflammation; Inflammatory response; Interleukin 6; Intervertebral disc degeneration; Intervertebral discs; Ligustilide; NF-κB; NF-κB protein; Nitric-oxide synthase; Nuclei (cytology); Nucleus pulposus; Rodents; Signal transduction; Therapeutic applications; Tumor necrosis factor-α
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.01.004

Intervertebral disc degeneration is a multifactorial and complicated degenerative disease that imposes a huge economic burden on society. However, there is no effective treatment that can delay and reverse the progression of disc degeneration. The inflammatory response causes the death of nucleus pulposus cells and the degradation of extracellular matrix are main factors of intervertebral disc degeneration. Ligustilide is a bioactive phthalide that is said to have an anti-inflammatory effect and anti-apoptosis effect on various disorders. Therefore, we further explored the protective effect of ligustilide on intervertebral disc degeneration and its potential mechanism. In this study, we found that ligustilide inhibited apoptosis, suppressed the expression of related inflammatory mediators (iNOS and COX-2) and decreased the expression of inflammatory cytokines (TNF-a and IL-6) in nucleus pulposus cells under IL-1β stimulation. At the same time, the degradation of extracellular matrix of nucleus pulposus cells induced by IL-1β was inhibited. In addition, we also found that ligustilide inhibits the inflammation response by inhibiting the NF-κB signaling pathway. Moreover, TUNEL assay and histological analysis showed that ligustilide could inhibit the apoptosis of nucleus pulposus cells and ameliorate the progression of intervertebral disc degeneration in punctured Rat IDD model. In summary, ligustilide may become a new potential treatment for intervertebral disc degeneration. •Ligustilide attenuated IL-1β induced apoptosis，inflammation response and ECM degradation in NP cells.•Potential protective mechanism of ligustilide was associated with the inhibition of NF-κB signaling pathway.•ligustilide ameliorate the IDD in vivo and become a new potential therapeutic for intervertebral disc degeneration