ArticlePharmaceutics2023
Permeability of Metformin across an In Vitro Blood-Brain Barrier Model during Normoxia and Oxygen-Glucose Deprivation Conditions: Role of Organic Cation Transporters (Octs).
Article in Pharmaceutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Metformin Enhances Antioxidant Defenses and Limits Lipid Peroxidation Through the Modulation of Nrf2/KEAP1 Pathway in Hippocampal Neurons Exposed to Amyloid-β Oligomers.Neurotoxicity research · 2026Article
- BBB-Permeable PROTACs: Where Do We Stand?ACS medicinal chemistry letters · 2026Review
- Metformin Suppresses Glioblastoma Tumor Growth and Progression Through the AMPK/FoxO3a/Survivin Axis.Cells · 2026Article
- Old Drug, New Science: Metformin and the Future of Pharmaceutics.Pharmaceutics · 2026Review
- Endothelial ferroptosis in blood-brain barrier dysfunction and neuroinflammation: mechanisms and immune-vascular crosstalk.Frontiers in immunology · 2026Review
- Metformin's protection against blood-brain barrier disruption and neuronal dysfunction under oxygen-glucose deprivation and tobacco smoke and e-vape chemical exposure.Fluids and barriers of the CNS · 2025Article
- Activation of the AMPK Signaling and Brain Function: A Friend or Foe?Journal of neurochemistry · 2025Review
- Proteomic Analysis Uncovers Enhanced Inflammatory Phenotype and Distinct Metabolic Changes in IDH1 Mutant Glioma Cells.International journal of molecular sciences · 2025Article
- Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress.Cells · 2025Review
- Insulin and Metformin are Associated With Reduced Risk of Amyotrophic Lateral Sclerosis.Chronic diseases and translational medicine · 2025Article
- Overview of Metformin and Neurodegeneration: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- AMPK Phosphorylates LMX1b to Regulate a Brainstem Neurogenic Network Important for Control of Breathing in Neonatal Mice.International journal of molecular sciences · 2024Article
- Review
- Diverse Applications of the Anti-Diabetic Drug Metformin in Treating Human Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- A Highly Sensitive UPLC-MS/MS Method for the Quantification of the Organic Cation Transporters' Mediated Metformin Uptake and Its Inhibition in Cells.Molecules (Basel, Switzerland) · 2024Article
- Metformin ameliorates neuroinflammatory environment for neurons and astrocytes during in vitro and in vivo stroke and tobacco smoke chemical exposure: Role of Nrf2 activation.Redox biology · 2024Article
- Mechanistic Insights on Metformin and Arginine Implementation as Repurposed Drugs in Glioblastoma Treatment.International journal of molecular sciences · 2024Article
- The role of Nrf2 signaling pathways in nerve damage repair.Toxicology research · 2024Review
- Beneficial effects of metformin treatment on memory impairment.Molecular biology reports · 2024Review
- Characterization of a Nonselective Opioid Receptor Functional Antagonist: Implications for Development as a Novel Opioid Dependence Medication.ACS pharmacology & translational science · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Our lab previously established that metformin, a first-line type two diabetes treatment, activates the Nrf2 pathway and improves post-stroke recovery. Metformin's brain permeability value and potential interaction with blood-brain barrier (BBB) uptake and efflux transporters are currently unknown. Metformin has been shown to be a substrate of organic cationic transporters (Octs) in the liver and kidneys. Brain endothelial cells at the BBB have been shown to express Octs; thus, we hypothesize that metformin uses Octs for its transport across the BBB. We used a co-culture model of brain endothelial cells and primary astrocytes as an in vitro BBB model to conduct permeability studies during normoxia and hypoxia using oxygen-glucose deprivation (OGD) conditions. Metformin was quantified using a highly sensitive LC-MS/MS method. We further checked Octs protein expression using Western blot analysis. Lastly, we completed a plasma glycoprotein (P-GP) efflux assay. Our results showed that metformin is a highly permeable molecule, uses Oct1 for its transport, and does not interact with P-GP. During OGD, we found alterations in Oct1 expression and increased permeability for metformin. Additionally, we showed that selective transport is a key determinant of metformin's permeability during OGD, thus, providing a novel target for improving ischemic drug delivery.
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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 Socratic graph.