Resveratrol Alleviates Intervertebral Disc Degeneration by Targeting NCOA4-Mediated Ferritinophagy Through Dual Antioxidant and Anti-Inflammatory Effects

Mar 24, 2026Drug design, development and therapy

Resveratrol may reduce spinal disc wear by lowering iron-driven cell damage with antioxidant and anti-inflammatory actions

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Abstract

Multi-omics analysis identified 10 -related hub genes linked to intervertebral disc degeneration (IVDD).

  • NCOA4 and ACSL4, which drive ferroptosis, were found to be elevated in degenerated discs, while anti-ferroptotic factors GPX4 and FSP1 were reduced.
  • Dynamic shifts in nucleus pulposus cell (NPC) phenotypes during degeneration were associated with increased pro-inflammatory immune cell infiltration.
  • NCOA4 was shown to promote iron overload and lipid peroxidation by degrading ferritin, leading to increased oxidative damage.
  • Resveratrol demonstrated the ability to restore disc height and mitigate inflammation in rat models of IVDD by downregulating NCOA4.
  • Cellular studies indicated that resveratrol reduced LPS-induced NPC degeneration by blocking NCOA4-dependent , thus decreasing cell death.

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Key numbers

IL1B 2.3×
Inflammatory Factor Increase
Comparison of IL1B levels in degenerated vs. non-degenerated tissues.
10
Core Genes Identified
Total number of core genes associated with IVDD progression.
1.5×
DHI Recovery
Comparison of DHI before and after resveratrol treatment.

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