Evidence mapPaperPMID 40467581Full record

ArticleScientific reports2025

Network pharmacology-based study in polymetformin's new function of blocking ages/rage pathway curing diabetic complications.

Linghong Kong, Hui Wang, Weiwei Jiang, Yun Chen, Zhuoling Du, Qiong Zhang, Jianyue Dong, Changchun Zeng, Hanping Liu

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Linghong Kong *MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou, 510631, China.
Hui Wang *MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou, 510631, China.
Weiwei JiangMOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou, 510631, China.
Yun ChenMOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou, 510631, China.
Zhuoling DuMOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou, 510631, China.
Qiong ZhangMOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou, 510631, China.
Jianyue DongMOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou, 510631, China.
Changchun ZengDepartment of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China. zengchch@glmc.edu.cn.
Hanping LiuMOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou, 510631, China. liuhp@scnu.edu.cn.

Funding

Foundation for Innovative Research Groups of the National Natural Science Foundation of China [81671729]
6 · The paper itself

Abstract

Advanced Glycation End Products (AGEs) are the molecular mediators that contribute to the progression of diabetic complications. However, there is a paucity of research on effective AGEs inhibitors and strategies for blocking the AGEs-RAGE pathway. To solve the problem, we synthesized polymetformin (PL), which for the first time proved the ability to inhibit AGEs formation and block the AGEs-RAGE pathway to protect the vascular from being damaged. Based on gene ontology (GO) analysis and Kegg enrichment, we found that PL could antagonize AGEs. Molecular docking and dynamics analyses showed that PL formed stable structures with AGEs through electrostatic interactions and hydrogen bonding. PL treatment altered AGEs structures have been proven in FT-IR results. The study discovered that PL interacted with AGEs via both non-covalent and covalent modifications, altering AGEs' binding sites and antagonizing the AGEs-RAGE pathway. Immunofluorescence assays indicated lower levels of RAGE, IL-1β, and TNFα, while ROS assays demonstrated lower ROS levels, highlighting PL's inhibitory effects and biocompatibility. Our work underscores PL's potential to treat diabetic complications by elucidating its mechanism of action against the AGEs-RAGE pathway and inflammatory factors for the first time. This research provides insights for managing chronic illnesses linked to the AGEs-RAGE pathway beyond diabetes complications.

Indexed as

Diabetes ComplicationsGlycation End Products, AdvancedNetwork PharmacologyReceptor for Advanced Glycation End ProductsSignal TransductionHumansMolecular Docking SimulationMolecular Dynamics SimulationReactive Oxygen SpeciesGlycation End Products, AdvancedReactive Oxygen SpeciesReceptor for Advanced Glycation End ProductsAdvanced glycation End-productsAGEs-RAGE pathway.Endothelial dysfunctionPolymetformin

Identifiers

PMID40467581
PMCPMC12137698

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.