Urolithin A Attenuates Aging-Induced Liver Injury by Inhibiting Nur77 Ubiquitination and Degradation
Aging is accompanied by chronic low-grade inflammation (inflammaging), driving age-related diseases. Urolithin A (UA), a gut microbial metabolite, possesses anti-inflammatory properties, yet its mechanism in hepatic aging remains unclear. This study investigated UA's effects on aging-associated inflammation and the involvement of Nur77 in D-galactose-induced macrophage senescence and mouse liver aging models using molecular docking, Western blotting, and immunoprecipitation. UA alleviated cellular senescence markers (p53, p21), suppressed pro-inflammatory factors (IL-6, IL-1β), and elevated anti-inflammatory IL-10. Mechanistically, UA enhanced Nur77 protein stability by inhibiting MDM2-mediated ubiquitination and degradation, thereby restoring inflammatory homeostasis. In vivo, UA ameliorated D-gal-induced liver injury and modulated the hepatic Nur77-MDM2 axis. Conclusion: UA stabilizes Nur77 by inhibiting its ubiquitination, alleviating hepatic aging-associated inflammation. This study identifies the MDM2-Nur77 axis as a potential therapeutic target for hepatic aging.
Authors
- Chao Wu (ORCID: https://orcid.org/0000-0002-6193-4398)
- Xinyu Que (ORCID: https://orcid.org/0000-0002-4057-3255)
- Chao Chen (ORCID: https://orcid.org/0000-0002-7939-6241)
- Xuan Qin (ORCID: https://orcid.org/0009-0005-6462-938X)
- Yuan Xu
- Yongfen Bao
- Wentao Huang
- Lihua Qu
- Shigang Shan
- Haoxiang Ou
- Jiaqi Xiao
- Yaoyao Ma
Institutions
- Nanjing University of Chinese Medicine (CN)
- Hunan Normal University (CN)
- Diabetes Australia (AU)
- Hubei University of Science and Technology (CN)
- Ezhou Central Hospital (CN)
- Indiana University School of Medicine
Publication Details
- Journal
- Journal of Agricultural and Food Chemistry
- Published
- 2026-03-16
- DOI
- https://doi.org/10.1021/acs.jafc.5c17898
- Primary Topic
- Pomegranate: compositions and health benefits
- Type
- article
- Field-Weighted Citation Impact
- 0.00