Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 484, Issue 1, Pages 100-109Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2009.01.016
Keywords
Flavonoids; Neuroinflammation; Astrocytes; Microglia; Nitric oxide; Brain; iNOS; Neuron; MAP kinase
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/C518222/1, BB/F008953/1, BB/G005702/1]
- Medical Research Council [G0400278]
- Biotechnology and Biological Sciences Research Council [BB/F008953/1, BB/G005702/1, BB/C518222/1] Funding Source: researchfish
- Medical Research Council [G0400278] Funding Source: researchfish
- BBSRC [BB/G005702/1, BB/F008953/1] Funding Source: UKRI
- MRC [G0400278] Funding Source: UKRI
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Neuroinflammation plays an integral role in the progression of neurodegeneration. In this study we investigated the anti-inflammatory effects of different classes of flavonoids (flavanones, flavanols and anthocyanidins) in primary mixed glial cells. We found that the flavanones naringenin and hesperetin and the flavanols (+)-catechin and (-)-epicatechin, but not the anthocyanidins cyanidin and pelargonidin, attenuated LPS/IFN-gamma-induced TNF-alpha production in glial cells. Naringenin also inhibited LPS/IFN-gamma-induced iNOS expression and nitric oxide production in glial cells, thus showing the strongest anti-inflammatory activity among all flavonoids tested. Moreover, naringenin protected against inflammatory-induced neuronal death in a primary neuronal-glial co-culture system. Naringenin also inhibited LPS/IFN-gamma-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation and downstream signal transducer and activator of transcription-1 (STAT-1) in LPS/IFN-gamma stimulated primary mixed glial cells. Taken together, our results suggest that naringenin may produce an anti-inflammatory effect in LPS/IFN-gamma stimulated glial cells that may be due to its interaction with p38 signalling cascades and the STAT-I transcription factor. (C) 2009 Elseiver Inc. All rights reserved.
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