ArticleJournal of neuroinflammation2021
Phloretin suppresses neuroinflammation by autophagy-mediated Nrf2 activation in macrophages.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- A Systematic Review: Quercetin-Secondary Metabolite of the Flavonol Class, with Multiple Health Benefits and Low Bioavailability.International journal of molecular sciences · 2024Pooled it
- Phloretin as a functional feed bioactive in livestock: Biological role, biosynthesis, and practical applications.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- Mechanistic insights from experimental autoimmune encephalomyelitis into immune regulation, autophagy, gut microbiota, blood-brain barrier integrity, and NLRP3 inflammasome-mediated pyroptosis in multiple sclerosis: potential clinical implications.Frontiers in neuroscience · 2026Review
- Therapeutic Delivery of Phloretin by Mixed Emulsifier-Stabilized Nanoemulsion Alleviated Cerebral Ischemia/Reperfusion Injury.Pharmaceutics · 2025Article
- Phytochemicals as Epigenetic Modulators in Chronic Diseases: Molecular Mechanisms.Molecules (Basel, Switzerland) · 2025Review
- Valorization of Apple Pomace: Production of Phloretin Using a Bacterial Cellulose-Immobilized β-Glycosidase.ChemSusChem · 2025Article
- Phloretin attenuates inflammation induced by subarachnoid hemorrhage through regulation of the TLR2/MyD88/NF-kB pathway.Scientific reports · 2024Article
- Computational identification of natural senotherapeutic compounds that mimic dasatinib based on gene expression data.Scientific reports · 2024Article
- Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases.Frontiers in immunology · 2024Review
- Polyphenols, Autophagy and Neurodegenerative Diseases: A Review.Biomolecules · 2023Review
- Article
- Srs11-92, a ferrostatin-1 analog, improves oxidative stress and neuroinflammation via Nrf2 signal following cerebral ischemia/reperfusion injury.CNS neuroscience & therapeutics · 2023Article
- Role of macrophage autophagy in postoperative pain and inflammation in mice.Journal of neuroinflammation · 2023Article
- NLRP3 Inflammasome's Activation in Acute and Chronic Brain Diseases-An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes.Biomedicines · 2023Review
- A Review on Polyphenols inNutrients · 2023Review
- Recent Advances in Pharmaceutical Cocrystals: A Focused Review of Flavonoid Cocrystals.Molecules (Basel, Switzerland) · 2023Review
- Review
- Neuroprotective Effect of Phloretin in Rotenone-Induced Mice Model of Parkinson's Disease: Modulating mTOR-NRF2-p62 Mediated Autophagy-Oxidative Stress Crosstalk.Journal of Alzheimer's disease : JAD · 2023Article
- Phloretin enhances remyelination by stimulating oligodendrocyte precursor cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Therapeutic Potential and Pharmaceutical Development of a Multitargeted Flavonoid Phloretin.Nutrients · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundMacrophages play a dual role in neuroinflammatory disorders such as multiple sclerosis (MS). They are involved in lesion onset and progression but can also promote the resolution of inflammation and repair of damaged tissue. In this study, we investigate if and how phloretin, a flavonoid abundantly present in apples and strawberries, lowers the inflammatory phenotype of macrophages and suppresses neuroinflammation.
methodsTranscriptional changes in mouse bone marrow-derived macrophages upon phloretin exposure were assessed by bulk RNA sequencing. Underlying pathways related to inflammation, oxidative stress response and autophagy were validated by quantitative PCR, fluorescent and absorbance assays, nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice, western blot, and immunofluorescence. The experimental autoimmune encephalomyelitis (EAE) model was used to study the impact of phloretin on neuroinflammation in vivo and confirm underlying mechanisms.
resultsWe show that phloretin reduces the inflammatory phenotype of macrophages and markedly suppresses neuroinflammation in EAE. Phloretin mediates its effect by activating the Nrf2 signaling pathway. Nrf2 activation was attributed to 5' AMP-activated protein kinase (AMPK)-dependent activation of autophagy and subsequent kelch-like ECH-associated protein 1 (Keap1) degradation.
conclusionsThis study opens future perspectives for phloretin as a therapeutic strategy for neuroinflammatory disorders such as MS.
trial registrationNot applicable.
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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.