Eupatilin attenuates the senescence of nucleus pulposus cells and mitigates intervertebral disc degeneration via inhibition of the MAPK/NF-κB signaling pathway

• Published in: Frontiers in pharmacology Vol. 13; p. 940475
• Main Authors: Yang, Huan, Yang, Xiao, Rong, Kewei, Liang, Jiarong, Wang, Zhengting, Zhao, Jie, Zhang, Pu, Li, Yijie, Wang, Lihuan, Ma, Hui, Ye, Bin
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 03-11-2022
• Subjects: Eupatilin; extracellular matrix; inflammation; intervertebral disc degeneration; nucleus pulposus cells; Pharmacology; senescence
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2022.940475

Intervertebral disc degeneration (IDD) is the main cause of low back pain. An increasing number of studies have suggested that inflammatory response or the senescence of nucleus pulposus (NP) cells is strongly associated with the progress of IDD. Eupatilin, the main flavonoid extracted from
Artemisia
, was reported to be associated with the inhibition of the intracellular inflammatory response and the senescence of cells. However, the relationship between eupatilin and IDD is still unknown. In this study, we explored the role of eupatilin in tumor necrosis factor-α (TNF-α)-induced activation of inflammatory signaling pathways and NP cell senescence, in the anabolism and catabolism of NP cell extracellular matrix (ECM) and in the effect of the puncture-induced model of caudal IDD in the rat.
In vitro
, eupatilin significantly inhibited TNF-α-induced ECM degradation, downregulated the expression of related markers of NP cells (MMP3, MMP9, and MMP13), and upregulated the expression of
SOX9
and
COL2A1
. Furthermore, eupatilin reduced TNF-α-induced cell senescence by inhibiting the expression of the senescence of NP cell-related markers (p21 and p53). Mechanistically, ECM degradation and cell senescence were reduced by eupatilin, which inhibited the activation of MAPK/NF-κB signaling pathways. Consistent with the
in vitro
data, eupatilin administration ameliorated the puncture-induced model of caudal IDD in the rat. In conclusion, eupatilin can inhibit the inflammatory response and the senescence of NP cells, which may be a novel treatment strategy for IDD.