Farhadi S, Mohammadi S, AlKindi AY, Al-Amri IS. Therapeutic potential of elafibranor in alcohol-associated liver disease: Insights into macrophage modulation and fibrosis reduction. World J Biol Chem 2025; 16(1): 104535 [DOI: 10.4331/wjbc.v16.i1.104535]
Corresponding Author of This Article
Issa S Al-Amri, PhD, Associate Professor, Department of Biological Sciences and Chemistry, College of Arts and Sciences, University of Nizwa, P.O. Box 33, Birkat Al-Mouz, Nizwa 616, Ad Dākhilīyah, Oman. issa.alamri@unizwa.edu.om
Research Domain of This Article
Immunology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Biol Chem. Mar 5, 2025; 16(1): 104535 Published online Mar 5, 2025. doi: 10.4331/wjbc.v16.i1.104535
Therapeutic potential of elafibranor in alcohol-associated liver disease: Insights into macrophage modulation and fibrosis reduction
Samira Farhadi, Saeed Mohammadi, Abdulaziz Y AlKindi, Issa S Al-Amri
Samira Farhadi, Abdulaziz Y AlKindi, Issa S Al-Amri, Department of Biological Sciences and Chemistry, College of Arts and Sciences, University of Nizwa, Nizwa 616, Ad Dākhilīyah, Oman
Samira Farhadi, Saeed Mohammadi, Natural and Medical Sciences Research Center, University of Nizwa, Nizwa 616, Ad Dākhilīyah, Oman
Samira Farhadi, Department of Agricultural Biotechnology, Faculty of Agricultural Sciences, University of Guilan, Rasht 4188958643, Gīlān, Iran
Saeed Mohammadi, Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 4934174515, Golestān, Iran
Co-first authors: Samira Farhadi and Saeed Mohammadi.
Author contributions: Farhadi S and Mohammadi S conducted the literature review; AlKindi AY and Al-Amri IS wrote the manuscript. All authors contributed to the manuscript revision and have read and approved the final manuscript.
Conflict-of-interest statement: We have no financial relationships to disclose.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Issa S Al-Amri, PhD, Associate Professor, Department of Biological Sciences and Chemistry, College of Arts and Sciences, University of Nizwa, P.O. Box 33, Birkat Al-Mouz, Nizwa 616, Ad Dākhilīyah, Oman. issa.alamri@unizwa.edu.om
Received: December 31, 2024 Revised: February 23, 2025 Accepted: March 4, 2025 Published online: March 5, 2025 Processing time: 66 Days and 0.3 Hours
Abstract
Alcohol-associated liver disease (ALD) is a major global health concern, contributing to liver injury, morbidity, and mortality. Elafibranor (EFN), a dual peroxisome proliferator-activated receptor α/δ agonist, has shown promise as a therapeutic candidate in preclinical studies. EFN reduces liver fibrosis by inhibiting lipid accumulation, apoptosis, and inflammatory pathways (LPS/TLR4/NF-κB), while enhancing autophagy and antioxidant responses. It also improves intestinal barrier function and modulates gut microbiota, reducing endotoxin-producing bacteria and increasing beneficial species. By strengthening the intestinal barrier and suppressing pro-inflammatory mediators like tumor necrosis factor-alpha and interleukin-6, EFN mitigates hepatic stellate cell activation and fibrogenic signaling. Macrophages play a central role in ALD progression, and EFN’s ability to modulate macrophage activity further highlights its anti-inflammatory properties. This review emphasizes EFN’s dual-targeted approach, addressing both hepatic and intestinal dysfunctions, distinguishing it from conventional ALD treatments. While preclinical results are promising, EFN remains under clinical investigation, with ongoing trials evaluating its safety and efficacy. Future research should focus on elucidating EFN’s molecular mechanisms and advancing its clinical application to establish its therapeutic potential in human populations. EFN represents a novel, comprehensive strategy for ALD management, targeting both liver and gut pathologies.
Core Tip: Macrophages play a central role in the progression of alcohol-associated liver disease (ALD), from initial liver injury to advanced stages like cirrhosis. Elafibranor (EFN), a dual peroxisome proliferator-activated receptor α/δ agonist, offers a promising therapeutic approach by reducing liver fibrosis, inhibiting macrophage activation, and suppressing TLR4/NF-κB inflammatory pathways. Additionally, EFN strengthens intestinal barrier function, addressing key drivers of ALD. With its dual anti-inflammatory and fibrosis-reducing effects, EFN holds potential for ALD and other liver diseases characterized by chronic inflammation and fibrosis. Further research is needed to validate its clinical applications.
