ArticleMetabolic brain disease2015
Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia.
Article in Metabolic brain disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 250 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
- Protective Effects of Metformin and Memantine Against Arsenic-Induced Neurotoxicity: Insights from In-Silico and In-Vivo Studies.Biological trace element research · 2026Article
- AMPK-NLRP3 Inflammasome Crosstalk: Structural Insights, Molecular Mechanisms, and Therapeutic Implications for Inflammation and Neuroinflammation.Molecular neurobiology · 2026Review
- Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy.FEBS open bio · 2026Article
- Extracellular vesicles: Revolutionizing targeted therapy for ischemic stroke.Acta pharmaceutica Sinica. B · 2026Review
- Metformin Repurposing in Neurological Disorders: A Clinical Trial Landscape.Annals of neurosciences · 2026Article
- Oxidative Stress and Its Role in Vascular Damage and Atherosclerosis.International journal of molecular sciences · 2026Review
- Metformin Improves Cognitive Function in a Rat Model of Global Cerebral Ischemia/Reperfusion Injury Via Inhibiting NF-kb Signaling Pathway and Caspase-1/NLRP3 Inflammasome.Molecular neurobiology · 2026Article
- Metformin Beyond Glycemic Control: Cardiovascular Protection and Diabetes Prevention.Journal of cardiovascular development and disease · 2026Review
- The AMPK/GDF15 Axis: A Novel Target for the Neuroprotective Effects of Metformin in Ischemic Stroke.Molecular neurobiology · 2025Review
- Modulation of the Oxidative Stress and ICAM-1/TLR4/NF-Κβ Levels by Metformin in Intestinal Ischemia/Reperfusion Injury in Rats.Cell biochemistry and biophysics · 2025Article
- Article
- Metformin and chloroquine enhanced the efficacy of cytarabine in acute lymphoblastic leukemia cell lines: a drug repositioning approach.Scientific reports · 2025Article
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Sugammadex Safely Reduces Total Intubation Time in the Intensive Care Unit Following Coronary Artery Bypass Grafting (CABG) at a Real-World Community Hospital.Journal of clinical medicine · 2025Article
- Exploring the protective role of metformin and dehydrozingerone in sodium fluoride-induced neurotoxicity: evidence from prenatal rat models.3 Biotech · 2025Article
- Impact of Prior Metformin Use on Stroke Outcomes: A Systematic Review and Updated Meta-Analysis.Journal of clinical medicine research · 2025Article
- The adjunctive role of metformin in patients with mild to moderate ulcerative colitis: a randomized controlled study.Frontiers in pharmacology · 2025Article
- Metabolic Homeostasis of Immune Cells Modulates Cardiovascular Diseases.Research (Washington, D.C.) · 2025Review
- Maternal Metformin Administration During the Pre-Gestation Period Improves Transient Cerebral Ischemia Injury in Male Offspring Rats.Advanced pharmaceutical bulletin · 2024Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Global cerebral ischemia arises in patients who have a variety of clinical conditions including cardiac arrest, shock and asphyxia. In spite of advances in understanding of the brain ischemia and stroke etiology, therapeutic approaches to improve ischemic injury still remain limited. It has been established that metformin can attenuate cell death in cerebral ischemia. One of the main functions of metformin is proposed to be conducted via AMP-activated protein kinase (AMPK)-dependent pathway in the experimental cerebral ischemia model. It is also established that metformin can suppress inflammation and activate Nuclear factor erythroid 2-related factor (Nrf2) pathways in neurons. In the current study, the role of metformin in regulating inflammatory and antioxidant pathways in the global cerebral ischemia was investigated. Our results indicated that pretreatment of rats by metformin attenuated cellular levels of nuclear factor-κB, Tumor Necrosis Factor alpha and Cyclooxygenase-2 which are considered as three important proteins involved in the inflammation pathway. Pretreatment by metformin increased the level of Nrf2 and heme oxygenase-1 in the hippocampus of ischemic rats compared with untreated ischemic group. Moreover, pretreatment by metformin enhanced the level of glutathione and catalase activities compared with them in ischemic group. Such protective changes detected by metformin pretreatment were reversed by injecting compound c, an AMPK inhibitor. These findings suggested that metformin might protect cells through modulating inflammatory and antioxidant pathways via induction of AMPK. However, more experimental and clinical trial studies regarding neuroprotective potential of metformin and the involved mechanisms, especially in the context of cerebral ischemic injuries, are necessary.
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