Int Immunopharmacol. 2026 Mar 29;178:116559. doi: 10.1016/j.intimp.2026.116559. Online ahead of print.
ABSTRACT
BACKGROUND: Intervertebral disc degeneration (IDD) is the main reason for lower back pain, it has a vicious circle that ECM degradation, inflammation, and cell death. Ferroptosis is a kind of iron-reliant regulated cell death brought about by lipid peroxidation, it has come to be a major player in the loss of nucleus pulposus (NP) cells. Importantly, ferroptosis releases DAMPs that promote local sterile inflammation, creating a positive feedback loop of pathogenesis. Epigallocatechin gallate (EGCG) which is a major component of green tea has anti-inflammatory and antioxidant effects, however, whether it has a potential to target ferroptosis and inflammatory signaling in IDD is unknown.
METHODS: An in vitro model of LPS-stimulated rat NP cells, we studied the impact of EGCG on the viability, inflammation (IL-1β, IL-6), ECM metabolism (COL2A1, ACAN), and ferroptosis markers (GPX4, SLC7A11, ACSL4, LPCAT3). ROS, GSH, MDA, mitochondrial ultrastructure. In vivo therapeutic effect was assessed by histological examination (H & E, Safranin O - Fast Green) and immunofluorescence in rat needle - puncture IDD model. Mechanisms were worked out via RNA-seq and Western blot.
RESULTS: EGCG protected NP cells from LPS - induced injury. Then, it lessened inflammatory cytokine creation; then, it did result in anabolic ECM gene expression, and also it sternly put a stop to ferroptosis. This was reflected in reduced iron loading, reduced lipid peroxidation (reduced MDA, increased GSH), and reversed expression of ferroptosis related proteins (upregulated GPX4, SLC7A11; downregulated ACSL4, LPCAT3). EGCG preserved normal mt morphology. In vivo,EGCG improved the degeneration of the disc and kept NP tissue architecture, ECM component expression was also upregulated. Mechanistically, RNA-seq and biochemical analysis found out that EGCG's protection was caused by blocking the MAPK signaling pathway, a central control center for inflammation and ferroptosis.
CONCLUSION: From our conclusion, in IDD, it was observed that the protection offered by EGCG was mainly inflammation and Ferrip-tosis of NP cells to avoid the process of MAPK pathway. Collectively, these results indicate that EGCG ameliorates IDD by attenuating inflammation and ferroptosis in NP cells, primarily through inhibition of the MAPK signaling pathway.
PMID:41911645 | DOI:10.1016/j.intimp.2026.116559