ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1710380
Curcumin Attenuates Liver Injury by Modulating the AGE–RAGE Axis and Metabolic Homeostasis in High-Fat Diet/Streptozotocin-Induced Type 2 Diabetic Mice
Provisionally accepted
Mengyao Li1
Chunmei Zhang1Junyu Ma1Bangzhao Zeng1Xuexun Li1Xin Zhao1
Xiaoyan Bi1Rong Li1Qin Gao2Yang Jiang1*
Fuli Ya1*- 1Dali University, Dali, China
- 2Jining Medical University, Jining, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Diabetic liver injury is a serious complication of type 2 diabetes mellitus (T2DM). Curcumin (CUR), a natural polyphenol derived from Curcuma longa, exhibits diverse biological activities. This study investigated the hepatoprotective effect of CUR against liver injury in a high-fat diet/streptozotocin (HFD/STZ)-induced T2DM mouse model and elucidated the underlying mechanisms. Methods: We integrated network pharmacology to identify common targets between CUR and T2DM, followed by molecular docking to evaluate binding affinities to key targets. In vivo, T2DM mice induced by HFD/STZ were administered dietary CUR (800 mg/kg diet) for 4 weeks. Hepatic oxidative stress, inflammatory markers, key signaling pathways, and metabolomic profiles were analyzed. Results: Network pharmacology revealed 256 overlapping targets between CUR and T2DM. Protein–protein interaction (PPI) analysis identified AKT1, TNF, TP53, IL-6, and EGFR as central hub targets. KEGG pathway enrichment suggested the involvement of the advanced glycation end products (AGE)–RAGE signaling pathway in the protective effects of CUR. Molecular docking demonstrated strong binding affinities of CUR with RAGE, AKT1, and TP53. In vivo, CUR supplementation significantly improved hyperglycemia and reduced hepatic oxidative stress and inflammation in T2DM mice. CUR inhibited the AGE–RAGE pathway and modulated downstream PI3K/Akt and NF‑κB signaling. UPLC‑MS/MS-based metabolomics analysis indicated that CUR altered metabolic pathways related to galactose, glycine/serine/threonine, propanoate, and nicotinate/nicotinamide. Conclusion: CUR protects against diabetic liver injury by inhibiting AGE–RAGE-induced inflammation and metabolic dysregulation. The protective mechanism involves modulation of the AGE–RAGE axis and restoration of metabolic homeostasis.
Keywords: Curcuma longa, Curcumin, diabetic liver injury, type 2 diabetes mellitus, AGE-RAGE signaling, Metabolomics
Received: 22 Sep 2025; Accepted: 10 Oct 2025.
Copyright: © 2025 Li, Zhang, Ma, Zeng, Li, Zhao, Bi, Li, Gao, Jiang and Ya. 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:
Yang Jiang, yangjiang@dali.edu.cn
Fuli Ya, yafuli@yeah.net
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.