Regulation of NF-Κb Activity in Astrocytes: Effects of Flavonoids at Dietary-Relevant Concentrations

Spilsbury, Alison; Vauzour, David; Spencer, Jeremy P.E.; Rattray, Marcus

doi:10.1016/j.bbrc.2012.01.081

Cited by 32Flavonoids in Medical ResearchPhytochemicals and Antioxidant ActivitiesNF-κB Signaling Pathways

Regulation of NF-Κb Activity in Astrocytes: Effects of Flavonoids at Dietary-Relevant Concentrations

Spilsbury, Alison, Vauzour, David, Spencer, Jeremy P.E., Rattray, Marcus·2012·Biochemical and Biophysical Research Communications

DOI 10.1016/j.bbrc.2012.01.081

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Abstract

Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Sustained activation of nuclear transcription factor κB (NF-κB) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-κB signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNFα, 150 ng/ml) increased NF-κB-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative IκBα construct. In addition, TNFα increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-κB activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1-1 μM) for 18 h. None of the flavonoids modulated constitutive or TNFα-induced NF-κB activity. Therefore, we conclude that NF-κB signalling in astrocytes is not a major target for flavonoids.

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Phytochemicals including flavonoids, polyphenols, terpenoids, and carotenoids target multiple signaling pathways responsible for microglial activation and release of pro-inflammatory mediators, or NF-κB and p38 MAPK activation.
“Many phytochemicals including flavonoids and other polyphenols, terpenoids, and carotenoids have indeed the ability to target multiple signaling pathways responsible for microglial activation and the subsequent release of pro-inflammatory mediators, or those involved in the activation of NF-κB and p38 MAPK”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Spilsbury et al., 2012

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Neuroinflammation: Modulation by flavonoids and mechanisms of action
Spencer, J. P. E., Vafeiadou, K., Williams, R. J., & Vauzour, D. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.10.016 · Cited by 315 · see citing works
Neuroinflammation and its Modulation by Flavonoids
Vafeiadou, K., Vauzour, D., & Spencer, J. P. E. (2007) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/187153007781662521 · Cited by 83 · see citing works

Authors: Spilsbury, A., Vauzour, D., Spencer, J. P. E., & Rattray, M.
Affiliations: University of Reading (GB)
Corresponding author: Rattray, Marcus
ORCID: Vauzour, David
Spencer, Jeremy P.E.
Rattray, Marcus
Venue: Biochemical and Biophysical Research Communications
Publisher: Elsevier BV
Published: 2012-02
Volume: 418
Issue: 3
Pages: 578-583
ISSN: 0006-291X (ISSN-L)
DOI: 10.1016/j.bbrc.2012.01.081
OpenAlex: W2080841042
Cited by: 32
References: 43
Citations by year: 2026: 2 · 2024: 1 · 2022: 2 · 2021: 4 · 2020: 3 · 2018: 2 · 2017: 2 · 2015: 3 · 2014: 2 · 2013: 8 · 2012: 3
FWCI: 3.77
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biochemical and Biophysical Research Communications (publishedVersion)
PubMed (publishedVersion)
Bradford Scholars (University of Bradford) (submittedVersion)
UEA Digital Repository (University of East Anglia) (submittedVersion)
Funders: Medical Research Council
Topics: Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: NF-κB signaling, astrocytes, flavonoids, dietary flavonoids, neuroinflammation, neurodegenerative diseases, TNF-α, IκBα, p65 nuclear translocation, epicatechin, catechins, luteolin, chrysin, kaempferol, naringenin, hesperetin, anti-inflammatory activity
MeSH terms: Animals, Astrocytes, Catechin, Cells, Cultured, Diet, Flavonoids, Phosphorylation, Tumor Necrosis Factor-alpha, Down-Regulation, NF-kappa B, Protein Transport, Mice, Transcription Factor RelA

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Regulation of NF-Κb Activity in Astrocytes: Effects of Flavonoids at Dietary-Relevant Concentrations

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