ArticlePloS one2012
Neuroprotective and anti-inflammatory effects of the flavonoid-enriched fraction AF4 in a mouse model of hypoxic-ischemic brain injury.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Extended local anesthesia enabled by flavonoid permeation enhancers.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Chemical Profile and In Vitro Protective Effects ofPlants (Basel, Switzerland) · 2025Article
- Targeting signaling pathways in neurodegenerative diseases: Quercetin's cellular and molecular mechanisms for neuroprotection.Animal models and experimental medicine · 2025Review
- Flavonoids as therapeutic agents for epilepsy: unveiling anti-inflammatory and antioxidant pathways for novel treatments.Frontiers in pharmacology · 2024Review
- Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study.European journal of drug metabolism and pharmacokinetics · 2023Article
- A Comprehensive Review on Anti-Inflammatory Response of Flavonoids in Experimentally-Induced Epileptic Seizures.Brain sciences · 2023Review
- Favorable Effects of Virgin Coconut Oil on Neuronal Damage and Mortality after a Stroke Incidence in the Stroke-Prone Spontaneously Hypertensive Rat.Life (Basel, Switzerland) · 2022Article
- Dietary Polyphenols as Therapeutic Intervention for Alzheimer's Disease: A Mechanistic Insight.Antioxidants (Basel, Switzerland) · 2022Review
- The role of TNFTNFα/p53 pathway in endometrial cancer mouse model administered with apple seed extract.Histology and histopathology · 2022Article
- Vitamin-Containing Antioxidant Formulation Reduces Carcinogen-Induced DNA Damage through ATR/Chk1 Signaling in Bronchial Epithelial Cells In Vitro.Biomedicines · 2021Article
- Therapeutic Effects of Hydroalcoholic Extracts from the Ancient Apple Mela Rosa dei Monti Sibillini in Transient Global Ischemia in Rats.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Integrated Metabolomic and Transcriptomic Analysis Reveals the Flavonoid Regulatory Network byInternational journal of molecular sciences · 2021Article
- Review
- Neuroprotective Effects of Quercetin in Alzheimer's Disease.Biomolecules · 2019Review
- Potential Therapeutic Targets of Quercetin and Its Derivatives: Its Role in the Therapy of Cognitive Impairment.Journal of clinical medicine · 2019Review
- Apple Peel Flavonoid Fraction 4 Suppresses Breast Cancer Cell Growth by Cytostatic and Cytotoxic Mechanisms.Molecules (Basel, Switzerland) · 2019Article
- Apple Flavonoids Suppress Carcinogen-Induced DNA Damage in Normal Human Bronchial Epithelial Cells.Oxidative medicine and cellular longevity · 2017Article
- Arabidopsis thaliana extracts optimized for polyphenols production as potential therapeutics for the APOE-modulated neuroinflammation characteristic of Alzheimer's disease in vitro.Scientific reports · 2016Article
- The role of flavonoids on oxidative stress in epilepsy.Oxidative medicine and cellular longevity · 2015Review
- Modulation of paraoxonase 2 (PON2) in mouse brain by the polyphenol quercetin: a mechanism of neuroprotection?Neurochemical research · 2013Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report here neuroprotective and anti-inflammatory effects of a flavonoid-enriched fraction isolated from the peel of Northern Spy apples (AF4) in a mouse of model of hypoxic-ischemic (HI) brain damage. Oral administration of AF4 (50 mg/kg, once daily for 3 days) prior to 50 min of HI completely prevented motor performance deficits assessed 14 days later that were associated with marked reductions in neuronal cell loss in the dorsal hippocampus and striatum. Pre-treatment with AF4 (5, 10, 25 or 50 mg/kg, p.o.; once daily for 3 days) produced a dose-dependent reduction in HI-induced hippocampal and striatal neuron cell loss, with 25 mg/kg being the lowest dose that achieved maximal neuroprotection. Comparison of the effects of 1, 3 or 7 doses of AF4 (25 mg/kg; p.o.) prior to HI revealed that at least 3 doses of AF4 were required before HI to reduce neuronal cell loss in both the dorsal hippocampus and striatum. Quantitative RT-PCR measurements revealed that the neuroprotective effects of AF4 (25 mg/kg; p.o.; once daily for 3 days) in the dorsal hippocampus were associated with a suppression of HI-induced increases in the expression of IL-1β, TNF-α and IL-6. AF4 pre-treatment enhanced mRNA levels for pro-survival proteins such as X-linked inhibitor of apoptosis and erythropoietin following HI in the dorsal hippocampus and striatum, respectively. Primary cultures of mouse cortical neurons incubated with AF4 (1 µg/ml), but not the same concentrations of either quercetin or quercetin-3-O-glucose or its metabolites, were resistant to cell death induced by oxygen glucose deprivation. These findings suggest that the inhibition of HI-induced brain injury produced by AF4 likely involves a transcriptional mechanism resulting from the co-operative actions of various phenolics in this fraction which not only reduce the expression of pro-inflammatory mediators but also enhance pro-survival gene signalling.
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