Modulatory Effects of Flavonoids on IL-4/IL-13 in Atopic Dermatitis and Their Structure-activity Relationships

Abstract:

[Objective] This study aims to explore the ameliorating effects of flavonoids on atopic dermatitis (AD) and their structure-activity relationships. [Method] Flavonoids were selected through network pharmacology with interleukin-4 (IL-4) and interleukin-13 (IL-13) as key targets. The immunoglobulin E (IgE)-induced RBL-2H3 cell model was employed to evaluate the effects of flavonoids on inflammatory factors, degranulation activities, and calcium ion influx, and the structure-activity relationships were analyzed. Finally, molecular docking was utilized to assist in exploring the action mechanism. [Result] All of the six flavonoids (luteolin, apigenin, chrysin, quercetin, kaempferol, and fisetin) screened by network pharmacology had significant inhibitory effects on the expression of IL-4, IL-13, tumor necrosis factor-α (TNF-α), cell degranulation, and calcium ion influx. Among them, flavonoids with a hydroxyl group at the C-5 position and without hydroxyl groups at the C-3 and C-3’ positions (apigenin and chrysin) exhibited the strongest inhibitory activities. Flavonoids without a hydroxyl group at the C-3 position of the C ring (luteolin, apigenin, and chrysin) had relatively strong binding energy with signal pathways such as PLCγ, Lyn, and ERK. [Conclusion] This study provided new ideas for the development of dietary therapies for preventing and ameliorating AD.