title: The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury.
abstract: 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.
authors.affiliation: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG2 6AP, UK.
authors.forename: Katerina
authors.initials: K
authors.lastname: Vafeiadou
authors.forename: David
authors.initials: D
authors.lastname: Vauzour
authors.forename: Hung Yi
authors.initials: HY
authors.lastname: Lee
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez-Mateos
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Williams
authors.forename: Jeremy P E
authors.initials: JP
authors.lastname: Spencer
mesh_terms: 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
chemical_list: D044950:Flavanones; D008070:Lipopolysaccharides; D050794:STAT1 Transcription Factor; D007371:Interferon-gamma; D006569:Hesperidin; D048051:p38 Mitogen-Activated Protein Kinases; C005273:naringenin; C013015:hesperetin