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Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study
Jerome J A Hendriks1, Helga E de Vries, Susanne M A van der Pol
1Department of Molecular Cell Biology, VU Medical Centre, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. jja.hendriks.cell@med.vu.nl
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.
Insights
Flavonoids like luteolin, quercetin, and fisetin were found to reduce myelin phagocytosis by macrophages. This suggests potential therapeutic benefits for limiting demyelination in multiple sclerosis.
Area of Science:
- Neuroimmunology
- Pharmacology
- Cell Biology
Background:
- Demyelination, a key feature of multiple sclerosis (MS), involves macrophages phagocytosing myelin and releasing inflammatory factors.
- This process exacerbates the neuro-inflammatory condition, highlighting a critical target for therapeutic intervention.
Purpose of the Study:
- To investigate the in vitro effects of flavonoids on myelin phagocytosis by macrophages.
- To identify specific flavonoid structures that modulate this process and explore their antioxidant properties.
Main Methods:
- Utilized a macrophage cell line to assess myelin phagocytosis in the presence of various flavonoids.
- Determined half-maximal inhibitory concentration (IC50) values and correlated flavonoid structure with inhibitory capacity.
- Assessed flavonoid antioxidant potency and its relation to myelin phagocytosis inhibition.
Main Results:
- Luteolin, quercetin, and fisetin significantly reduced myelin phagocytosis by macrophages without impacting cell viability.
- Effective flavonoids possessed specific structural features: hydroxyl groups at B-3 and B-4 positions with a C-2,3 double bond.
- Inhibitory capacity correlated strongly with antioxidant potency, suggesting a role for reactive oxygen species in myelin phagocytosis.
Conclusions:
- Flavonoids demonstrate potential in modulating macrophage-mediated myelin phagocytosis.
- Specific flavonoid structures and their antioxidant activity are key to inhibiting this process.
- These findings suggest flavonoids could be explored as a therapeutic strategy to limit demyelination in multiple sclerosis.