Panaxynol from dietary sources modulates ferroptosis through ceRNA networks in synovium: a novel strategy for alleviating rheumatoid arthritis through functional food intervention†

Abstract

Panaxynol (PAL), a bioactive polyacetylene abundant in dietary plants such as carrots and ginseng, has shown potential in mitigating immune-related diseases, including rheumatoid arthritis (RA). This study investigates the anti-RA effects of PAL through ferroptosis induction and anti-inflammatory mechanisms. In vitro experiments revealed that PAL significantly reduced the viability of collagen-induced arthritis fibroblast-like synoviocytes (CIA-FLS) by triggering ferroptosis, as evidenced by decreased glutathione (GSH) levels, increased lipid peroxidation (LPO) and iron accumulation, and downregulation of key ferroptosis regulators (SLC7A11, GPX4). Furthermore, PAL inhibited the NF-κB pathway, leading to reduced secretion of pro-inflammatory cytokines (TNF-α, IL-1β). In vivo studies using a CIA rat model demonstrated that PAL alleviated joint swelling, reduced the arthritis index, and improved trabecular bone density, highlighting its therapeutic potential. Transcriptomic analysis revealed that PAL modulated ferroptosis and NF-κB signaling through ceRNA networks, with experimental validation confirming the involvement of TFR1 and NIK axes. Notably, inflammatory factors were found to attenuate the sensitivity of CIA-FLS to PAL-induced ferroptosis, suggesting a complex interplay between inflammation and cell death regulation. These findings not only elucidate the mechanism of PAL in RA mitigation but also underscore its potential as a dietary intervention for chronic inflammatory diseases. By integrating traditional dietary knowledge with modern functional food science, this study provides a theoretical basis for the development of functional foods rich in PAL to support joint health.