The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury.
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-1 transcription factor.
Vafeiadou
Katerina
K
Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG2 6AP, UK.
Vauzour
David
D
Lee
Hung Yi
HY
Rodriguez-Mateos
Ana
A
Williams
Robert J
RJ
Spencer
Jeremy P E
JP
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D044950:Flavanones / Q000494:pharmacology*; D006569:Hesperidin / Q000494:pharmacology; D007249:Inflammation / Q000517:prevention & control*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009457:Neuroglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D044950:Flavanones; D008070:Lipopolysaccharides; D050794:STAT1 Transcription Factor; D007371:Interferon-gamma; D006569:Hesperidin; D048051:p38 Mitogen-Activated Protein Kinases; C005273:naringenin; C013015:hesperetin