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World J Diabetes. Apr 15, 2026; 17(4): 114679
Published online Apr 15, 2026. doi: 10.4239/wjd.v17.i4.114679
Published online Apr 15, 2026. doi: 10.4239/wjd.v17.i4.114679
Hyperoside attenuates diabetic nephropathy by activating the Nrf2/SLC7A11/GPX4 axis to restrain ferroptosis
Chao Liu, Yan Li, Shi-Feng Yang, Department of Nephrology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Yuan Zhang, Ming Gao, Department of Nephrology, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an 710004, Shaanxi Province, China
Author contributions: Liu C and Li Y performed the research; Liu C, Zhang Y, and Gao M collected and analyzed the data; Liu C and Yang SF drafted the manuscript; Yang SF designed the research; and all authors critically reviewed and approved the final version of the article.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Health Science Center of Xi’an Jiaotong University, approval No. XJTUAE2025-3549.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Corresponding author: Shi-Feng Yang, MD, Department of Nephrology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an 710061, Shaanxi Province, China. jeffysy@126.com
Received: September 26, 2025
Revised: November 1, 2025
Accepted: February 5, 2026
Published online: April 15, 2026
Processing time: 200 Days and 18.2 Hours
Revised: November 1, 2025
Accepted: February 5, 2026
Published online: April 15, 2026
Processing time: 200 Days and 18.2 Hours
Core Tip
Core Tip: This study, for the first time, demonstrates that hyperoside, a natural flavonoid, protects against diabetic nephropathy by suppressing ferroptosis via activation of the Nrf2/SLC7A11/GPX4 antioxidant axis. In high-glucose-challenged HK-2 cells, hyperoside restored glutathione, reduced lipid reactive oxygen species and Fe2+ accumulation, and improved cell viability, effects comparable to ferrostatin-1. In streptozotocin-induced diabetic nephropathy rats, hyperoside ameliorated renal dysfunction and histologic injury while upregulating Nrf2/SLC7A11/GPX4. These findings provide mechanistic and experimental support for hyperoside as a potential therapeutic candidate for diabetic nephropathy.