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World J Diabetes. May 15, 2026; 17(5): 117635
Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.117635
Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.117635
Zuo Gui pill alleviates M1 macrophage polarization in type 2 diabetic osteoporosis through the Nrf2/HO-1/XCT/GPX4 pathway
Yi Zhao, Xiu-Zhi Feng, Wen-Qi Cao, Yi-Ran Chen, Ying Yang, Jing-Chi Liu, Ao Xu, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning Province, China
Yan-Ling Ren, Zhi-Min Wang, Liaoning University of Traditional Chinese Medicine Affiliated Hospital, Shenyang 110847, Liaoning Province, China
Co-first authors: Yi Zhao and Xiu-Zhi Feng.
Co-corresponding authors: Yan-Ling Ren and Zhi-Min Wang.
Author contributions: Zhao Y and Feng XZ contributed equally to this study and were involved in conceptualization, methodology, data curation, visualization, and writing the original draft as co-first authors; Cao WQ, Chen YR, Yang Y, Liu JC, and Xu A contributed to validation and formal analysis; Ren YL and Wang ZM were involved in reviewing and editing, resources, supervision, funding acquisition, and project administration as co-corresponding authors; All authors read and approved the final version of the manuscript to be published.
Supported by National Natural Science Foundation of China, No. 82174260; and Liaoning Provincial Department of Science and Technology Joint Fund for Doctoral Research Initiation Project, No. 2023-BSBA-224.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals [Liaoning Academy of Traditional Chinese Medicine (No. LZYY240404)].
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
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: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Yan-Ling Ren, Professor, Liaoning University of Traditional Chinese Medicine Affiliated Hospital, No. 79 Chongshandong Road, Shenyang 110847, Liaoning Pro
Received: December 16, 2025
Revised: January 8, 2026
Accepted: February 24, 2026
Published online: May 15, 2026
Processing time: 150 Days and 20 Hours
Revised: January 8, 2026
Accepted: February 24, 2026
Published online: May 15, 2026
Processing time: 150 Days and 20 Hours
Core Tip
Core Tip: Regulation of M1 polarization of bone marrow macrophages in type 2 diabetic osteoporosis is dependent on the activation of the nuclear factor E2-related factor 2/hemoxygenase-1/XCT/glutathione peroxidase 4 signaling pathway. Zuo Gui pill, metformin, and Fer-1 can work synergistically to restore nuclear factor E2-related factor 2, upregulate hemoxygenase-1, and inhibit M1 polarization of bone marrow macro