Emodin mitigates rheumatoid arthritis through direct binding to TNF-α

• DOI: 10.3389/fphar.2025.1520281
• Publication Date: 2025-02-26T07:25:26Z
• Authors: Dingyan Lu; Xudong Tian; Taotao Cao; Shuaishuai Chen; Chunhua Liu; Lin Zheng; Meng Zhou; Xiaoyan Peng; Yongjun Li; Ting Liu
• Keywords: rheumatoid arthritis; TNF-α binding; TNF-α-TNFR1 interaction; NF-κB pathway inhibition; Therapeutics. Pharmacology; RM1-950; emodin

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 emodin and elucidate potential mechanisms, with a specific focus on identifying molecular targets. Employing collagen-induced (CIA) rat model, along transcriptomic analysis, thermal proteome profiling (TPP) TNF-α-induced L929 cell was confirmed, TNF-α as target. Techniques such drug affinity responsive target stability (DARTS), cellular shift assay (CETSA), Affinity ultrafiltration-liquid chromatography/mass spectrometry (AUF-LC/MS), surface plasmon resonance (SPR) bio-layer interferometry (BLI) validated binding TNF-α. Molecular dynamics simulation, ELISA BLI further revealed that stabilizes asymmetric trimeric structure TNF-α, disrupting TNF-α-TNFR1 interaction. In vitro assays, including luciferase reporter gene MH7A demonstrated this disruption inhibits NF-κB activation, leading downregulation inflammatory mediators IL-6, IL-1β, COX2. conclusion, directly targets stabilizing blocking interaction, which subsequently suppresses downstream pathway activation contributes potent properties.