Marein protects human nucleus pulposus cells against high glucose-induced injury and extracellular matrix degradation at least partly by inhibition of ROS/NF-κB pathway

Int Immunopharmacol. 2020 Mar:80:106126. doi: 10.1016/j.intimp.2019.106126. Epub 2020 Jan 10.

Abstract

Intervertebral disc degeneration (IDD), a major cause of discogenic low back pain, is a musculoskeletal disorder involving the apoptosis of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) degradation. Marein is a major active flavonoid ingredient extracted from the hypoglycemic plant Coreopsis tinctoria with several beneficial biological activities including anti-diabetic effects. Nevertheless, there are no reports concerning the effects of marein on IDD. Our study aimed to evaluate the effects of marein on high glucose (HG)-induced injury and ECM degradation in human NPCs (HNPCs). CCK-8 assay was applied to evaluate cell viability. Flow cytometry analysis, a cell death detection ELISA, and caspase-3 activity assay were used to assess apoptosis. The mRNA expression of ECM-related proteins matrix metalloproteinase (MMP)-3, MMP-13, Collagen II, and aggrecan were determined by qRT-PCR. The changes of the nuclear factor-kappa B (NF-κB) pathway were examined by western blot. Stimulation with HG significantly reduced cell viability and induced apoptosis in HNPCs. Moreover, HG exposure increased MMP-3 and MMP-13 expression and decreased Collagen II and aggrecan expression in HNPCs. Notably, marein effectively alleviated HG-induced viability reduction, apoptosis and ECM degradation in HNPCs. We also found that marein inhibited HG-induced ROS generation and NF-κB activation in HNPCs. Inhibition of NF-κB pathway reinforced HG-induced injury and ECM degradation in HNPCs. In summary, marein protected HNPCs against HG-induced injury and ECM degradation at least partly by inhibiting the ROS/NF-κB pathway.

Keywords: Extracellular matrix degradation; High glucose; Marein; Nucleus pulposus cells; ROS/NF-κB pathway.

MeSH terms

  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chalcones / pharmacology*
  • Extracellular Matrix / drug effects*
  • Glucose / adverse effects*
  • Humans
  • Intervertebral Disc Degeneration
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Nucleus Pulposus / cytology
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Chalcones
  • NF-kappa B
  • Reactive Oxygen Species
  • marein
  • Glucose