ArticleBritish journal of pharmacology2011
Metformin inhibits HMGB1 release in LPS-treated RAW 264.7 cells and increases survival rate of endotoxaemic mice.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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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.
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Who cites it
75 citing papers in PubMed, 156 citations in OpenAlex.
- Novel genetic insights into causal effects of potential metformin targets and immune mediation on sepsis.Biology direct · 2026Article
- The central role of IL-6 in the differential effects of GLP-1 receptor agonists and metformin across multiple health conditions.Frontiers in immunology · 2026Review
- Nociceptor α7nAChR activation blunts neuronal HMGB1 release and attenuates inflammation and nociceptive behavior.Molecular medicine (Cambridge, Mass.) · 2025Article
- Article
- Roles of the Receptor for Advanced Glycation End Products and Its Ligands in the Pathogenesis of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction.International journal of molecular sciences · 2024Review
- Therapeutic strategies targeting mechanisms of macrophages in diabetic heart disease.Cardiovascular diabetology · 2024Review
- The anti-inflammatory effect of metformin: The molecular targets.Genes to cells : devoted to molecular & cellular mechanisms · 2024Review
- Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment.International journal of molecular sciences · 2023Review
- Dioleoylphosphatidylglycerol Inhibits Heat Shock Protein B4 (HSPB4)-Induced Inflammatory Pathways In Vitro.International journal of molecular sciences · 2023Article
- Berberine in Sepsis: Effects, Mechanisms, and Therapeutic Strategies.Journal of immunology research · 2023Review
- Metformin pretreatment ameliorates busulfan-induced liver endothelial toxicity during haematopoietic stem cell transplantation.PloS one · 2023Article
- New potential for an old kid on the block: Impact of premorbid metformin use on lactate kinetics, kidney injury and mortality in sepsis and septic shock, an observational study.Endocrinology, diabetes & metabolism · 2023Observational
- Role of High Mobility Group Box 1 in Cardiovascular Diseases.Inflammation · 2022Review
- Metformin attenuated sepsis-associated liver injury and inflammatory response in aged mice.Bioengineered · 2022Article
- Metformin: Activation of 5' AMP-activated protein kinase and its emerging potential beyond anti-hyperglycemic action.Frontiers in genetics · 2022Review
- High Mobility Group Proteins in Sepsis.Frontiers in immunology · 2022Review
- Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies.Frontiers in oncology · 2022Review
- Immune dysfunction in developmental programming of type 2 diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- Metformin, Macrophage Dysfunction and Atherosclerosis.Frontiers in immunology · 2021Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeRecently, metformin, a well-known anti-diabetic drug, has been shown to possess anti-inflammatory activities. This study investigated the effect of metformin on the expression of pro-inflammatory cytokines including high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)-treated animals and cells. EXPERIMENTAL APPROACH: We investigated whether metformin inhibits the release of HMGB1 in LPS-treated RAW 264.7 cells and increases survival rate in endotoxaemic mice (lethal endotoxaemia was induced by an i.p. injection of LPS). This was achieved by a range of techniques including Western blotting, enzyme-linked immunosorbent assay, specific pharmacological inhibitors, knock out of α(1) -subunit of AMP-activated protein kinase (AMPK) and recombinant HMGB1. KEY
resultsBoth pre- and post-treatment with metformin significantly improved survival of animals during lethal endotoxaemia (survival rate was monitored up to 2 weeks), decreased serum levels of tumour necrosis factor-alpha (TNF-α), interleukin-1β, HMGB1 expression and myeloperoxidase activity in lungs. However, metformin failed to improve survival in endotoxaemic animals that had additionally been treated with recombinant HMGB1. In an in vitro study, metformin dose-dependently inhibited production of pro-inflammatory cytokines and HMGB1 release. Metformin activated AMPK by its phosphorylation. Compound C (pharmacological inhibitor of AMPK) and siAMPKα1 reversed the anti-inflammatory effect of metformin in LPS-treated cells. CONCLUSIONS AND IMPLICATIONS: Our data indicate that metformin significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Metformin improved survival in a mouse model of lethal endotoxaemia by inhibiting HMGB1 release. AMPK activation was implicated as one of the mechanisms contributing to this inhibition of HMGB1 secretion.
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Registered trials
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.