@article{Liu2025, 
author = {Titi Liu and Meiyan Duan and Jin Li and Wei Dong and Yingqi Yin and Honglei Hui and Jing Xu and Zhe Jiang and Chunxia Gan and Zemin Xiang and Jun Sheng and Xuanjun Wang and Huanhuan Xu},
title = {Stephanine interacts with TNF-α to block NF-κB signaling and protects against rheumatoid arthritis},
year = {2025},
journal = {Food Science and Human Wellness},
volume = {14},
number = {7},
pages = {9250551},
keywords = {Stephanine, TNF-α-tumor necrosis factor receptor interaction, NF-κB signaling, Rheumatoid arthritis},
url = {https://www.sciopen.com/article/10.26599/FSHW.2025.9250551},
doi = {10.26599/FSHW.2025.9250551},
abstract = {Tumor necrosis factor-α (TNF-α) is a key player in the pathogenesis of rheumatoid arthritis (RA) and considered a promising target for therapeutic drug development. Activation of the nuclear factor-kappa B (NF-κB) pathway upon TNF-α binding to its receptor is crucial for progression of RA. Stephanine (SA), an isoquinoline aporphine-type alkaloid recently identified in Stephania plants, exhibits anti-inflammatory properties, but its underlying mechanisms of action are unknown at present. In this study, we explored whether SA could ameliorate RA through inhibition of the NF-κB signaling pathway in association with TNF-α activity. Our experiments revealed a binding affinity (KD) of SA for TNF-α of 2.934 × 10−6 mol/L. Additionally, SA at a concentration of 10 μmol/L effectively hindered the binding of TNF-α to its receptors tumor necrosis factor receptor 1 (TNFR1) and TNFR2. In vitro, SA prevented TNF-α-induced death of L929 cells and blocked NF-κB activation triggered by TNF-α in 293-TNF-α responsive, as well as human fibroblast-like synoviocytes (HFLS) and human RA fibroblast-like synoviocytes (MH7A) cell lines. Furthermore, in a collagen-induced arthritis (CIA) mouse model, SA alleviated the symptoms of RA through suppression of NF-κB signaling. Our collective findings support the therapeutic efficacy of SA, a natural compound targeting TNF-α, in the management of RA.}
}