Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Sustained activation of nuclear transcription factor ?B (NF-?B) 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-?B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNFa, 150 ng/ml) increased NF-?B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I?Ba construct. In addition, TNFa increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-?B activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin hydrate), 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 TNFa-induced NF-?B activity. Therefore, we conclude that NF-?B signalling in astrocytes is not a major target for flavonoids.
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 17 Feb 2012|