Evidence map›Paper›PMID 31998447›Full record

ArticleOxidative medicine and cellular longevity2020

Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule.

Haoli Wang, Zhilong Zheng, Wen Han, Yuan Yuan, Yao Li, Kailiang Zhou, Qingqing Wang, Ling Xie, Ke Xu, Hongyu Zhang and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Oxidative medicine and cellular longevity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 4 pooled it
6.5field-weighted citation impact, top 2% of its field
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

59 citing papers in PubMed, 4 syntheses or guidelines pooled it, 90 citations in OpenAlex.

  1. Pooled it
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  11. Indole-3-propionic acid promotes Schwann cell proliferation following peripheral nerve injury by activating the PI3K/AKT pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
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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

13 authors at 2 institutions in 1 country.

Haoli WangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID https://orcid.org/0000-0003-0694-2341
Zhilong ZhengMolecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Wen HanMolecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yuan YuanMolecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yao LiDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Kailiang ZhouDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Qingqing WangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Ling XieMolecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Ke XuThe Institute of Life Sciences, Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Biomedical Collaborative Innovation Center of Wenzhou, Wenzhou University, Wenzhou, Zhejiang, China 325035.
Hongyu ZhangMolecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Huazi XuDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yanqing WuThe Institute of Life Sciences, Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Biomedical Collaborative Innovation Center of Wenzhou, Wenzhou University, Wenzhou, Zhejiang, China 325035.ORCID https://orcid.org/0000-0001-6535-6655
Jian XiaoMolecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID https://orcid.org/0000-0001-7374-6506
Wenzhou Medical University · CNWenzhou University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spinal cord injury (SCI) is a devastating disease that may lead to lifelong disability. Thus, seeking for valid drugs that are beneficial to promoting axonal regrowth and elongation after SCI has gained wide attention. Metformin, a glucose-lowering agent, has been demonstrated to play roles in various central nervous system (CNS) disorders. However, the potential protective effect of metformin on nerve regeneration after SCI is still unclear. In this study, we found that the administration of metformin improved functional recovery after SCI through reducing neuronal cell apoptosis and repairing neurites by stabilizing microtubules via PI3K/Akt signaling pathway. Inhibiting the PI3K/Akt pathway with LY294002 partly reversed the therapeutic effects of metformin on SCI in vitro and vivo. Furthermore, metformin treatment weakened the excessive activation of oxidative stress and improved the mitochondrial function by activating the nuclear factor erythroid-related factor 2 (Nrf2) transcription and binding to the antioxidant response element (ARE). Moreover, treatment with Nrf2 inhibitor ML385 partially abolished its antioxidant effect. We also found that the Nrf2 transcription was partially reduced by LY294002 in vitro. Taken together, these results revealed that the role of metformin in nerve regeneration after SCI was probably related to stabilization of microtubules and inhibition of the excessive activation of Akt-mediated Nrf2/ARE pathway-regulated oxidative stress and mitochondrial dysfunction. Overall, our present study suggests that metformin administration may provide a potential therapy for SCI.

Indexed as

MicrotubulesSpinal Cord InjuriesAnimalsAxonsChromonesMetforminMitochondriaMorpholinesNF-E2-Related Factor 2Oxidative StressPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyRegenerationResponse Elements2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneChromonesMetforminMorpholinesNfe2l2 protein, ratNF-E2-Related Factor 2Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-akt

Identifiers

PMID31998447
PMCPMC6969994
OpenAlexW2999285937

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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 OpenQuestion graph.