Publication Name	World Journal of Diabetes
Manuscript ID	109568
Country	China

Category	Integrative & Complementary Medicine
Manuscript Type	Basic Study
Article Title	Nephroprotective mechanism of Kunkui Baoshen decoction: Targeting the HERC2/NCOA4-mediated autophagy-dependent ferroptosis pathway in diabetic kidney disease
Manuscript Source	Unsolicited Manuscript
All Author List	Si-Yuan Song, Chu-Chu Shan, Pei-Pei Zhou, Wei-Long Xu, Ying Tan, Xi-Qiao Zhou, Li-Ji Huang, Qian-Hua Yan and Jiang-Yi Yu
Funding Agency and Grant Number	Funding Agency Grant Number National Natural Science Foundation of China 82205025 National Natural Science Foundation of China 82374355 National Natural Science Foundation of China 82174293
Corresponding Author	Jiang-Yi Yu, MD, Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Qinhuai District, Nanjing 210000, Jiangsu Province, China. 1401743118@qq.com
Key Words	Ubiquitination; Ferroptosis; Diabetic kidney disease; Renal fibrosis; Kunkui Baoshen decoction
Core Tip	Kunkui Baoshen decoction (KKBS), a traditional Chinese herbal formula, exerts renoprotective effects in DKD by inhibiting autophagy-dependent ferroptosis. Through integrated transcriptomic and metabolomic analyses, we identified the Homologous to E6-AP C-terminus and RCC1-like domain-containing E3 ubiquitin protein ligase/nuclear receptor coactivator 4 axis as a critical therapeutic target. KKBS enhances Homologous to E6-AP C-terminus and RCC1-like domain-containing E3 ubiquitin protein ligase-mediated K48-linked ubiquitination of nuclear receptor coactivator 4, promoting its degradation and thereby suppressing ferroptosis, renal inflammation, and fibrosis in high glucose-induced human kidney-2 cells and db/db mice. This research reveals a novel pathway through which KKBS regulates ferroptosis to prevent DKD progression.
Citation	Song SY, Shan CC, Zhou PP, Xu WL, Tan Y, Zhou XQ, Huang LJ, Yan QH, Yu JY. Nephroprotective mechanism of Kunkui Baoshen decoction: Targeting the HERC2/NCOA4-mediated autophagy-dependent ferroptosis pathway in diabetic kidney disease. World J Diabetes 2025; In press

Received	2025-05-15 02:24
Peer-Review Started	2025-05-16 00:19
To Make the First Decision
Return for Revision	2025-05-27 11:09
Revised	2025-06-03 08:06
Second Decision	2025-08-13 05:12
Accepted by Journal Editor-in-Chief	2025-08-13 06:23
Accepted by Executive Editor-in-Chief	2025-08-15 10:39
Articles in Press	2025-08-15 10:39
Publication Fee Transferred	2025-06-09 14:43
Edit the Manuscript by Language Editor	2025-08-17 01:44
Typeset the Manuscript

ISSN	1948-9358 (online)
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