Li B. Microglial metabolic reprogramming: Aucubin inhibits aldose reductase to reverse diabetic neuropathic pain. World J Diabetes 2025; 16(8): 110285 [DOI: 10.4239/wjd.v16.i8.110285]
Corresponding Author of This Article
Bin Li, PhD, Full Professor, Institution of Compared Medicine, Yangzhou University, No. 88 South Daxue Road, Yangzhou 225009, Jiangsu Province, China. 008480@yzu.edu.cn
Research Domain of This Article
Cell Biology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Bin Li, Institution of Compared Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, China
Bin Li, Center for Integrative Physiology and Molecular Medicine, University of Saarland, Homburg 66424, Saarland, Germany
Author contributions: Li B contributed to the manuscript writing, reviewing, and editing, participated in the formal analysis, conceptualization, project administration.
Supported by the Top-level Talents Support Program of Yangzhou University; “Lv Yang Jin Feng” Outstanding Doctor of Yangzhou, No. YZLYJFJH2023YXBS169; and Natural Science Foundation of Jiangsu Province, No. BK20240907.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bin Li, PhD, Full Professor, Institution of Compared Medicine, Yangzhou University, No. 88 South Daxue Road, Yangzhou 225009, Jiangsu Province, China. 008480@yzu.edu.cn
Received: June 4, 2025 Revised: June 15, 2025 Accepted: July 14, 2025 Published online: August 15, 2025 Processing time: 71 Days and 22.6 Hours
Abstract
This letter critically comments on the article by Zheng et al investigating the role of aucubin in alleviating diabetic neuropathic pain (DNP). DNP arises from hyperglycaemia-induced nerve injury and microglial reprogramming toward aerobic glycolysis. Aldose reductase (also known as AKR1B1) redirects excess glucose flux through the polyol pathway, thus increasing oxidative stress and inflammation. Zheng et al show that aucubin, a plant iridoid glycoside, reverses streptozotocin-induced mechanical and thermal hypersensitivity and anxiety-like behaviour in mice. Mechanistically, aucubin restores microglial morphology, reduces glycolytic flux, enhances oxidative phosphorylation and lowers tumour necrosis factor-α, interleukin (IL)-1β and IL-6 levels in spinal tissue and cultures of the BV-2 microglial cell line. Network pharmacology and molecular docking analyses identify AKR1B1 as a key target, confirmed by the fact that short hairpin RNA knockdown of AKR1B1 eliminates the effects of aucubin. Contrary to the other studies, this study uniquely implicates the polyol pathway in microglial immunometabolism.
Core Tip: Zheng et al have uncovered a new anti-neuropathic function of the plant glycoside aucubin-inhibiting aldose reductase and thus preventing hyperglycaemia-driven microglial aerobic glycolysis and inflammation associated with diabetic neuropathy. This study highlights a novel metabolism-immunity axis of diabetic neuropathic pain and offers an innovative therapeutic strategy.
