Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study.
Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease. Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds, are able to influence myelin phagocytosis by macrophages in vitro. The flavonoids luteolin, quercetin and fisetin most significantly decreased the amount of myelin phagocytosed by a macrophage cell line without affecting its viability. IC(50) values for these compounds ranged from 20 to 80 microM. The flavonoid structure appeared to be essential for observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4 positions in combination with a C-2,3 double bond were most effective. The capacity of the various flavonoids to inhibit phagocytosis correlated well with their potency as antioxidant, which is in line with the requirement of reactive oxygen species for the phagocytosis of myelin by macrophages. Our results implicate that flavonoids may be able to limit the demyelination process during multiple sclerosis.
Hendriks
Jerome J A
JJ
Department of Molecular Cell Biology, VU Medical Centre, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. jja.hendriks.cell@med.vu.nl
de Vries
Helga E
HE
van der Pol
Susanne M A
SM
van den Berg
Timo K
TK
van Tol
Eric A F
EA
Dijkstra
Christine D
CD
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
D005419:Flavonoids; D017382:Reactive Oxygen Species