Stephanine interacts with TNF-α to block NF-κB signaling and protects against rheumatoid arthritis
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. Stephanin...
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| Format: | Article |
| Language: | English |
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Tsinghua University Press
2025-07-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | https://www.sciopen.com/article/10.26599/FSHW.2025.9250551 |
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| author | Titi Liu Meiyan Duan Jin Li Wei Dong Yingqi Yin Honglei Hui Jing Xu Zhe Jiang Chunxia Gan Zemin Xiang Jun Sheng Xuanjun Wang Huanhuan Xu |
| author_facet | Titi Liu Meiyan Duan Jin Li Wei Dong Yingqi Yin Honglei Hui Jing Xu Zhe Jiang Chunxia Gan Zemin Xiang Jun Sheng Xuanjun Wang Huanhuan Xu |
| author_sort | Titi Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-be0cbbae6de146b8b7f30465f29beb2d |
| institution | Kabale University |
| issn | 2097-0765 2213-4530 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-be0cbbae6de146b8b7f30465f29beb2d2025-08-20T03:41:14ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302025-07-01147925055110.26599/FSHW.2025.9250551Stephanine interacts with TNF-α to block NF-κB signaling and protects against rheumatoid arthritisTiti Liu0Meiyan Duan1Jin Li2Wei Dong3Yingqi Yin4Honglei Hui5Jing Xu6Zhe Jiang7Chunxia Gan8Zemin Xiang9Jun Sheng10Xuanjun Wang11Huanhuan Xu12Key Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaDepartment of Obstetrics and Gynecology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaDepartment of Laboratory Medicine, Southern Central Hospital of Yunnan Province, The First People’s Hospital of Honghe State, Honghe 661100, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaKey Laboratory of Pu’er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, ChinaTumor 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.https://www.sciopen.com/article/10.26599/FSHW.2025.9250551stephaninetnf-α-tumor necrosis factor receptor interactionnf-κb signalingrheumatoid arthritis |
| spellingShingle | Titi Liu Meiyan Duan Jin Li Wei Dong Yingqi Yin Honglei Hui Jing Xu Zhe Jiang Chunxia Gan Zemin Xiang Jun Sheng Xuanjun Wang Huanhuan Xu Stephanine interacts with TNF-α to block NF-κB signaling and protects against rheumatoid arthritis Food Science and Human Wellness stephanine tnf-α-tumor necrosis factor receptor interaction nf-κb signaling rheumatoid arthritis |
| title | Stephanine interacts with TNF-α to block NF-κB signaling and protects against rheumatoid arthritis |
| title_full | Stephanine interacts with TNF-α to block NF-κB signaling and protects against rheumatoid arthritis |
| title_fullStr | Stephanine interacts with TNF-α to block NF-κB signaling and protects against rheumatoid arthritis |
| title_full_unstemmed | Stephanine interacts with TNF-α to block NF-κB signaling and protects against rheumatoid arthritis |
| title_short | Stephanine interacts with TNF-α to block NF-κB signaling and protects against rheumatoid arthritis |
| title_sort | stephanine interacts with tnf α to block nf κb signaling and protects against rheumatoid arthritis |
| topic | stephanine tnf-α-tumor necrosis factor receptor interaction nf-κb signaling rheumatoid arthritis |
| url | https://www.sciopen.com/article/10.26599/FSHW.2025.9250551 |
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