ArticleDrug design, development and therapy2011
Flavonoids targeting of IκB phosphorylation abrogates carcinogen-induced MMP-9 and COX-2 expression in human brain endothelial cells.
Article in Drug design, development and therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The Neuroprotective Role of Fisetin in Different Neurological Diseases: a Systematic Review.Molecular neurobiology · 2023Pooled it
- Clinical Translation of Fisetin for Age-Related Diseases: Current Evidence and Future Opportunities.Nutrients · 2026Review
- Natural Compounds TargetingNutrients · 2025Review
- Much More than Nutrients: The Protective Effects of Nutraceuticals on the Blood-Brain Barrier in Diseases.Nutrients · 2025Review
- Therapeutic Expedition of Luteolin against Brain-related Disorders: An Updated Review.Combinatorial chemistry & high throughput screening · 2025Review
- Exploring the Role of Apigenin in Neuroinflammation: Insights and Implications.International journal of molecular sciences · 2024Review
- Biological Properties and Antimicrobial Potential of Cocoa and Its Effects on Systemic and Oral Health.Nutrients · 2023Review
- Article
- Therapeutic Effects of Citrus Flavonoids Neohesperidin, Hesperidin and Its Aglycone, Hesperetin on Bone Health.Biomolecules · 2022Review
- Effects of Natural Polyphenols on Oxidative Stress-Mediated Blood-Brain Barrier Dysfunction.Antioxidants (Basel, Switzerland) · 2022Review
- CO-Releasing Molecule (CORM)-3 Ameliorates Spinal Cord-Blood Barrier Disruption Following Injury to the Spinal Cord.Frontiers in pharmacology · 2020Article
- A Transcriptional Regulatory Role for the Membrane Type-1 Matrix Metalloproteinase in Carcinogen-Induced Inflammasome Gene Expression.Gene regulation and systems biology · 2017Article
- Apigenin Attenuates Experimental Autoimmune Myocarditis by Modulating Th1/Th2 Cytokine Balance in Mice.Inflammation · 2016Article
- HMG-CoA reductase inhibitory activity and phytocomponent investigation of Basella alba leaf extract as a treatment for hypercholesterolemia.Drug design, development and therapy · 2015Article
- Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer.Bioinformation · 2015Article
- Article
- A Role for the Cavin-3/Matrix Metalloproteinase-9 Signaling Axis in the Regulation of PMA-Activated Human HT1080 Fibrosarcoma Cell Neoplastic Phenotype.Cancer growth and metastasis · 2014Article
- MT1-MMP expression level status dictates the in vitro action of lupeol on inflammatory biomarkers MMP-9 and COX-2 in medulloblastoma cells.Inflammopharmacology · 2013Article
- The ETS-Domain Transcription Factor Elk-1 Regulates COX-2 Gene Expression and Inhibits Glucose-Stimulated Insulin Secretion in the Pancreatic β -Cell Line INS-1.International journal of endocrinology · 2013Article
- The Herbal Drug Melampyrum pratense L. (Koch): Isolation and Identification of Its Bioactive Compounds Targeting Mediators of Inflammation.Evidence-based complementary and alternative medicine : eCAM · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB). Increased BBB breakdown and brain injury are associated with neuroinflammation and are thought to trigger mechanisms involving matrix metalloproteinase upregulation. Emerging evidence also indicates that cyclooxygenase (COX) inhibition limits BBB disruption, but the mechanisms linking metalloproteinase to COX remain unknown. In this study, we sought to investigate the nuclear factor-kappa B (NF-κB) signaling pathway, a common pathway in both the regulation of matrix metalloproteinase-9 (MMP-9) and COX-2 expression, and the inhibitory properties of several chemopreventive flavonoids. Human brain microvascular endothelial cells were treated with a combination of phorbol 12-myristate 13-acetate (PMA), a carcinogen documented to increase MMP-9 and COX-2 through NF-κB, and several naturally occurring flavonoids. Among the molecules tested, we found that fisetin, apigenin, and luteolin specifically and dose-dependently antagonized PMA-induced COX-2 and MMP-9 gene and protein expressions as assessed by qRT-PCR, immunoblotting, and zymography respectively. We further demonstrate that flavonoids impact on IκK-mediated phosphorylation activity as demonstrated by the inhibition of PMA-induced IκB phosphorylation levels. Our results suggest that BBB disruption during neuroinflammation could be pharmacologically reduced by a specific class of flavonoids acting as NF-κB signal transduction inhibitors.
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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.