@article{Jiang2026, 
author = {Zhe Jiang and Titi Liu and Qiangqiang Zhu and Dengyou Nie and Ziyan Yang and Yun Zhang and Yanli Shen and Haiyun Ding and Hongkang Zhu and Baiqing Tian and Jun Sheng and Chenxia Zhang and Chaoyi Xue and Huanhuan Xu},
title = {Dietary polyphenol ellagic acid suppresses NF-κB signaling pathway in human synovial fibroblasts by disrupting the binding of TNF-α to its receptors: Insights from molecular interactions},
year = {2026},
journal = {Food Science and Human Wellness},
keywords = {Ellagic acid, TNF-α, TNFRs, NF-κB signaling, Molecular interactions},
url = {https://www.sciopen.com/article/10.26599/FSHW.2026.9251199},
doi = {10.26599/FSHW.2026.9251199},
abstract = {Tumor necrosis factor-α (TNF-α) is a key proinflammatory cytokine that drives rheumatoid arthritis (RA) pathogenesis by sustaining synovial inflammation and joint destruction via binding to its receptors (TNFR1 and TNFR2), making this interaction a core therapeutic target. Ellagic acid (EA), a dietary polyphenol naturally abundant in pomegranates, berries, and nuts, is well known for its anti-inflammatory and antioxidant properties. In this study, we investigated whether EA targets the TNF-α pathway using a combination of molecular interaction analyses and cellular assays. Surface plasmon resonance (SPR) revealed that EA binds directly to TNF-α (KD = 3.588 × 10-6 M), TNFR1 (KD = 6.488 × 10-6 M), and TNFR2 (KD = 7.952 × 10-6 M) with high affinity. Molecular dynamics simulations and competitive SPR assays demonstrated that EA disrupts the TNF-α–TNFR interaction. Functionally, EA (0.625–2.5 μM) suppressed TNF-α-induced apoptosis in L929 cells and inhibited TNF-α-triggered NF-κB activation in 293-TNF-α Res (NF-κB) cells. In RA-relevant cell models using human synovial fibroblasts (HFLS and MH7A), EA attenuated TNF-α-stimulated NF-κB signaling by reducing phosphorylation of IKKα/β, IκBα, and p65, and by blocking p65 nuclear translocation. Notably, EA did not inhibit LPS-induced NF-κB activation, indicating pathway selectivity. These findings demonstrate that EA inhibits NF-κB activation by directly targeting the TNF-α–TNFR interaction, highlighting its potential as a food-derived functional ingredient for managing RA and related inflammatory conditions.}
}