ArticleMolecular neurobiology2017
(-)-Epicatechin, a Natural Flavonoid Compound, Protects Astrocytes Against Hemoglobin Toxicity via Nrf2 and AP-1 Signaling Pathways.
Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Pooled it
- Cocoa flavanols, Nrf2 activation, and oxidative stress in peripheral artery disease: mechanistic findings in muscle based on outcomes from a randomized trial.American journal of physiology. Cell physiology · 2024Trial
- Acetylation-like H2BK109Q attenuates acute brain injury and preserves axon-myelin integrity after intracerebral hemorrhage.CNS neuroscience & therapeutics · 2026Article
- Targeting Insulin Signaling and TRAF2/JNK Pathway: A Comprehensive In Silico Study ofInternational journal of molecular sciences · 2026Article
- Plant-Derived Natural Compounds and Nrf2-Centered Redox Signaling in Intracerebral Hemorrhage: Evidence Grading, Mechanistic Boundaries, and Translational Challenges.Antioxidants (Basel, Switzerland) · 2026Review
- Unlocking the Power of Plant-Derived Natural Products: Therapeutic Benefits for Cognitive Health and Neuropsychiatric Symptoms in Dementia-Related Diseases.Plants (Basel, Switzerland) · 2026Review
- Catechins in stroke: multi-target mechanisms, preclinical evidence, and translational challenges.Frontiers in pharmacology · 2026Review
- Revitalizing Muscle Regeneration: Cocoa Polyphenols Shield Mitochondrial Integrity and Boost Myogenesis Under Oxidative Stress.Microscopy research and technique · 2025Article
- Traditional Chinese Medicine and Ferroptosis in Intracerebral Hemorrhage: A Potential Therapeutic Approach.Drug design, development and therapy · 2025Review
- Beyond oxidative stress: Ferroptosis as a novel orchestrator in neurodegenerative disorders.Frontiers in immunology · 2025Review
- Pharmacological Effects of Antioxidant Mycosporine-Glycine in Alleviating Ultraviolet B-Induced Skin Photodamage: Insights from Metabolomic and Transcriptomic Analyses.Antioxidants (Basel, Switzerland) · 2024Article
- Bone marrow-derived mesenchymal stem cell-derived exosome-loaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage.World journal of diabetes · 2024Article
- Influence of Alcohol on Intracerebral Hemorrhage: From Oxidative Stress to Glial Cell Activation.Life (Basel, Switzerland) · 2024Review
- Melatonin exerts neuroprotective effects in mice with spinal cord injury by activating the Nrf2/Keap1 signaling pathway via the MT2 receptor.Experimental and therapeutic medicine · 2024Article
- Improving outcomes in intracerebral hemorrhage through microglia/macrophage-targeted IL-10 delivery with phosphatidylserine liposomes.Biomaterials · 2023Article
- An enriched environment improves long-term functional outcomes in mice after intracerebral hemorrhage by mechanisms that involve the Nrf2/BDNF/glutaminase pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Role of Plant-Derived Compounds in the Molecular Pathways Related to Inflammation.International journal of molecular sciences · 2023Review
- The Role of Ferroptosis in Blood-Brain Barrier Injury.Cellular and molecular neurobiology · 2023Review
- The Role of Nrf2 in Relieving Cerebral Ischemia-Reperfusion Injury.Current neuropharmacology · 2023Review
- Nrf2 Activation: Involvement in Central Nervous System Traumatic Injuries. A Promising Therapeutic Target of Natural Compounds.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
(-)-Epicatechin is a brain-permeable, natural product found at high concentrations in green tea and cocoa. Our previous research has shown that (-)-epicatechin treatment reduces hemorrhagic stroke injury via nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in vivo. However, the mechanism of action of this compound in modulation of oxidant stress and in protection against hemoglobin-induced astrocyte injury is unclear. Therefore, we explored the cellular and molecular mechanisms that underlie these protective effects in vitro. Mouse primary astrocytes isolated from wild-type mice and Nrf2 knockout (KO) mice were preconditioned with hemoglobin to simulate intracerebral hemorrhage (ICH) in vitro. Effects of (-)-epicatechin were measured by Western blotting, immunostaining, MTT assay, and reactive oxidant stress (ROS) assay. (-)-Epicatechin increased Nrf2 nuclear accumulation and cytoplasmic levels of superoxide dismutase 1 (SOD1) in wild-type astrocytes but did not increase SOD1 expression in Nrf2 knockout (KO) astrocytes. Furthermore, (-)-epicatechin treatment did not alter heme oxygenase 1 (HO1) expression in wild-type astrocytes after hemoglobin exposure, but it did decrease HO1 expression in similarly treated Nrf2 KO astrocytes. In both wild-type and Nrf2 KO astrocytes, (-)-epicatechin suppressed phosphorylated JNK and nuclear expression of JNK, c-jun, and c-fos, indicating that inhibition of activator protein-1 (AP-1) activity by (-)-epicatechin is Nrf2-independent. These novel findings indicate that (-)-epicatechin protects astrocytes against hemoglobin toxicity through upregulation of Nrf2 and inhibition of AP-1 activity. These cellular and molecular effects may partially explain the cerebroprotection as we previously observed for (-)-epicatechin in animal models of ICH.
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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.