Evidence map›Paper›PMID 41359249›Full record

ArticleMolecular neurobiology2025

Metformin Alleviates Cognitive Impairment in Chronic-Phase Epileptic Rats by Modulating the TLR4/MyD88/NF-κB Pathway and Gut Flora Composition.

Kaiping Zhou, Yizheng Wang, Wanyue Sun, Zhuofeng Mao, Weiping Wang, Zhenzhen Qu

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

6 authors.

Kaiping ZhouChina Rehabilitation Research Center, Beijing, 100000, China.
Yizheng WangChina Rehabilitation Research Center, Beijing, 100000, China.
Wanyue SunChina Rehabilitation Research Center, Beijing, 100000, China.
Zhuofeng MaoKey Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 05000, China.
Weiping WangKey Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 05000, China.
Zhenzhen QuKey Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 05000, China. quzhzh@hebmu.edu.cn.

Funding

the National Natural Science Foundation of China 81671292the Natural Science Foundation of Hebei Province H2018206435the Project of Hebei Provincial Department of health NO.20180310
6 · The paper itself

Abstract

Epilepsy (EP) is characterized by recurring spontaneous seizures, often leading to long-standing cognitive impairment, significantly impacting the quality of life. Due to the unknown pathogenic pathways, developing effective treatments for epilepsy-associated cognitive impairment has been challenging. Metformin, a first-line oral antidiabetic drug, has proven effective in various EP models. Recent studies have shown that metformin can modulate gut microbiota composition and improve cognitive function. However, the protective effect of metformin on cognitive function in the chronic phase of epilepsy in rats is still unclear. Furthermore, whether its effect has to do with the gut microbiota remains to be determined. This study used the pilocarpine-induced chronic epilepsy model to mimic the pathological process of epilepsy-related cognitive impairment. Combined with 16 s rDNA sequencing and 4D-Label free proteomics analysis, multi-omics analysis was performed. We discovered that metformin treatment improved spatial learning and memory, reduced hippocampal neuronal damage, and enhanced synaptic plasticity in epileptic rats. Additionally, 16S rDNA sequencing revealed that metformin treatment reversed microbiota alterations associated with epilepsy, particularly by increasing the abundances of Alloprevotella, Blautia, Romboutsia, and Phascolarctobacterium, while reducing Prevotellaceae NK3B31 group and Ruminococcus 1. This modulation helped reduce the release of microbial toxins and promoted intestinal homeostasis maintenance. Further mechanistic studies involving proteomics and ELISA testing showed that metformin treatment inhibited the TLR4/MyD88/NF-κB pathway and alleviated systemic inflammation in epileptic rats. As can be seen, metformin therapy's amelioration of cognitive impairment in epilepsy may be facilitated by the gut microbiota, with the underlying mechanism potentially involving the suppression of TLR4/MyD88/NF-κB signaling and the mitigation of inflammation.

Indexed as

Cognitive DysfunctionEpilepsyGastrointestinal MicrobiomeMetforminMyeloid Differentiation Factor 88NF-kappa BSignal TransductionToll-Like Receptor 4AnimalsChronic DiseaseHippocampusMaleRatsRats, Sprague-DawleyMetforminMyd88 protein, ratMyeloid Differentiation Factor 88NF-kappa BTlr4 protein, ratToll-Like Receptor 4Cognitive impairmentEpilepsyGut floarMetforminTLR4/MyD88/NF-κB signaling pathway

Identifiers

What Socratic holds

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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.