Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity
relationship study.
Hendriks JJ, de Vries HE, van der Pol SM, van den Berg TK, van Tol EA,
Dijkstra CD
Biochem Pharmacol 2003 Mar 65:877-85
Abstract
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.
Author Address
Department of Molecular Cell Biology, VU Medical Centre, Van der
Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
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