@article{Gan2026, 
author = {Chunxia Gan and Titi Liu and Fei Chen and Jin Li and Jing Xu and Zhe Jiang and Hongkang Zhu and Chaoyi Xue and Jun Sheng and Huanhuan Xu},
title = {Natural compound DOCA blocks TNF-α/TNFR-driven NF-κB activation to ameliorate rheumatoid arthritis},
year = {2026},
journal = {Food Science and Human Wellness},
volume = {15},
number = {3},
pages = {9250909},
keywords = {Tumor necrosis factor-α (TNF-α), TNF-α receptor (TNFR), TNF-α-TNFR interaction, Nuclear factor–kappa B signaling, Rheumatoid arthritis},
url = {https://www.sciopen.com/article/10.26599/FSHW.2025.9250909},
doi = {10.26599/FSHW.2025.9250909},
abstract = {Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that has long been hampered by limited treatment efficacy and significant side effects. Tumor necrosis factor-α (TNF-α) plays a pivotal role in RA pathogenesis by binding to its receptor (TNFR) and activating the downstream nuclear factor-kappa B (NF-κB) signaling pathway, which promotes the transcription of pro-inflammatory genes and perpetuates disease progression. Blocking the TNF-α–TNFR interaction thus represents a promising therapeutic strategy for RA. In this study, we identified a natural compound, 1-norbetulonic acid (DOCA), that disrupts the binding between TNF-α and TNFR, leading to therapeutic benefits in RA. Our results show that DOCA inhibits TNF-α-induced activation of the NF-κB pathway in human fibroblast-like synoviocytes and MH7A cells, and prevents nuclear translocation of the p65 subunit. Notably, DOCA demonstrated significant therapeutic efficacy in a mouse model of RA. Together, these findings support the hypothesis that DOCA alleviates RA by blocking TNF-α–TNFR signaling, underscoring its potential as a natural product-derived inhibitor of this interaction and highlighting a viable approach for the discovery of TNF-α/TNFR-targeted natural therapeutics.}
}