ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1614978
Lumefantrine Ameliorates DSS-Induced Colitis by Targeting FLI-1 to Suppress NF-κB Signaling
Provisionally accepted
- 1College of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan Province, China
- 2Department of Clinical Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan Province, China
- 3Pidu district hospital of traditional chinese medicine, Chengdu, China
- 4School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan Province, China
- 5Second Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China
- 6The Second Affiliated Hospital of Chengdu Medical College · Nuclear Industry 416 Hospital, Chengdu, China
- 7Key Laboratory of target discovery and protein drug development in major diseases of Sichuan Higher Education institutes, Chengdu, Sichuan Province, China
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Lumefantrine, a synthetic small-molecule antimalarial drug with proven clinical efficacy, demonstrates novel therapeutic potential in inflammatory bowel disease (IBD). In a 3% dextran sulfate sodium (DSS)-induced murine IBD model, oral administration of Lumefantrine (20 mg/kg/day) for 7 days significantly attenuated disease activity index (DAI) scores and restored intestinal barrier integrity through upregulation of epithelial tight junction proteins Claudin-1 and ZO-1. Treated mice exhibited reduced serum levels of IL-1β, IL-6 and TNF-α, along with decreased colonic expression of inflammatory mediators cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNos). Mechanistically, molecular interaction analysis combined with pull-down assays identified FLI-1 -a transcription factor upregulated in IBD colon tissues -as Lumefantrine's direct binding target, mediating its suppression of NF-κB signaling in lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IEC-6, NCM460). Collectively, these findings establish Lumefantrine as a promising repurposed therapeutic candidate that ameliorates experimental colitis through FLI-1dependent inhibition of the NF-κB pathway.
Keywords: Lumefantrine, Fli-1, NF-κB, Inflammatory bowel disease (IBD), Colitis
Received: 20 Apr 2025; Accepted: 26 Jun 2025.
Copyright: © 2025 Yang, Guo, Luo, Tang, Liu and Ren. 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: Xiaolin Ren, The Second Affiliated Hospital of Chengdu Medical College · Nuclear Industry 416 Hospital, Chengdu, China
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