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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 |
doi: 10.3389/fphar.2025.1520281
Emodin mitigates rheumatoid arthritis through direct binding to TNF-α
Provisionally accepted
Dingyan Lu * Xudong Tian * Taotao Cao * Shuaishuai Chen * Chunhua Liu * Lin Zheng * Meng Zhou * Xiaoyan Peng * Yongjun Li *
Ting Liu *- Guizhou Medical University, Guiyang, Guizhou Province, China
Emodin has shown certain anti-rheumatoid arthritis (RA) activity in preliminary studies.However, the precise mechanisms of emodin's anti-RA effects, particularly its direct targets, remain unclear. This study aimed to evaluate the anti-RA activity of emodin and elucidate its potential mechanisms, with a specific focus on identifying its molecular targets. Employing a collagen-induced arthritis (CIA) rat model, along with transcriptomic analysis, thermal proteome profiling (TPP) and TNF-α-induced L929 cell model, the anti-RA activity of emodin was confirmed, identifying TNF-α as a potential target. Techniques such as drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), Affinity ultrafiltration-liquid chromatography/mass spectrometry (AUF-LC/MS), surface plasmon resonance (SPR)and bio-layer interferometry (BLI) validated the direct binding of emodin to TNF-α.Molecular dynamics simulation, ELISA and BLI further revealed that emodin stabilizes the asymmetric trimeric structure of TNF-α, disrupting the TNF-α-TNFR1 interaction.In vitro assays, including luciferase reporter gene assay and TNF-α-induced MH7A cell model, demonstrated that this disruption inhibits TNF-α-induced NF-κB activation, leading to the downregulation of inflammatory mediators such as IL-6, IL-1β, and COX2. In conclusion, emodin directly targets TNF-α, stabilizing its structure and blocking TNF-α-TNFR1 interaction, which subsequently suppresses downstream NF-κB pathway activation and contributes to its potent anti-RA properties.
Keywords: Emodin, Rheumatoid arthritis, TNF-α binding, TNF-α-TNFR1 interaction, NF-κB pathway inhibition
Received: 01 Nov 2024; Accepted: 03 Feb 2025.
Copyright: © 2025 Lu, Tian, Cao, Chen, Liu, Zheng, Zhou, Peng, Li and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Dingyan Lu, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
Xudong Tian, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
Taotao Cao, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
Shuaishuai Chen, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
Chunhua Liu, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
Lin Zheng, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
Meng Zhou, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
Xiaoyan Peng, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
Yongjun Li, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
Ting Liu, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
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