Berberine prevents human nucleus pulposus cells from IL‑1β‑induced extracellular matrix degradation and apoptosis by inhibiting the NF‑κB pathway

Int J Mol Med. 2019 Apr;43(4):1679-1686. doi: 10.3892/ijmm.2019.4105. Epub 2019 Feb 21.

Abstract

Intervertebral disc degeneration (IDD) is widely considered to be one of the main causes of lower back pain, which is a chronic progressive disease closely related to inflammation, nucleus pulposus (NP) cell apoptosis and extracellular matrix (ECM) degradation. Berberine (BBR) is an alkaloid compound with an anti‑inflammatory effect and has been reported to exert therapeutic action in several inflammatory diseases, including osteoarthritis. Therefore, it was hypothesized that BBR may have a therapeutic effect on IDD through inhibition of the inflammatory response. The aim of the present study was to evaluate the influence of BBR on IDD in interleukin (IL)‑1β‑treated human NP cells in vitro. The results showed that BBR attenuated the upregulation of ECM‑catabolic factors [matrix metalloproteinase (MMP)‑3, MMP‑13, a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)‑4 and ADAMTS‑5], and the downregulation of ECM‑anabolic factors (type II collagen and aggrecan) following stimulation of the human NP cells with IL‑1β. Treatment with BBR also protected human NP cells from IL‑1β‑induced apoptosis, as determined by western blotting and flow cytometry. Mechanistically, the IL‑1β‑stimulated degradation of IκBα, and the phosphorylation and translocation of nuclear factor (NF)‑κB p65 were found to be attenuated by BBR, indicating that NF‑κB pathway activation was suppressed by BBR in the IL‑1β‑treated human NP cells. The results of the experiments revealed a therapeutic potential of BBR for the prevention or treatment of IDD.

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis / drug effects*
  • Berberine / pharmacology*
  • Cell Survival / drug effects
  • Cytoprotection / drug effects
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Humans
  • Interleukin-1beta / adverse effects*
  • Models, Biological
  • NF-kappa B / metabolism*
  • Nucleus Pulposus / cytology*
  • Signal Transduction / drug effects*
  • Young Adult

Substances

  • Interleukin-1beta
  • NF-kappa B
  • Berberine