黄酮类化合物对特应性皮炎中IL-4/IL-13的调节作用及构效关系

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

摘要:

【目的】 探究黄酮类化合物对特应性皮炎（atopic dermatitis，AD）的改善作用及其构效关系。 【方法】 以白细胞介素-4（interleukin-4，IL-4）和白细胞介素-13（interleukin-13，IL-13）为关键靶点，通过网络药理学筛选黄酮类化合物。在免疫球蛋白 E（immunoglobulin E，IgE）介导的RBL-2H3细胞模型中，评价其对炎症因子、细胞脱颗粒活性和钙离子内流的影响，并分析构效关系，最后利用分子对接技术辅助探究其作用机制。 【结果】 网络药理学筛选出的6种黄酮类化合物（木犀草素、芹菜素、白杨素、槲皮素、山柰酚、漆黄素）均能够显著抑制IL-4、IL-13、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）的表达、细胞脱颗粒和钙离子内流。其中C-5位含有羟基、C-3和C-3’位无羟基的黄酮类化合物（芹菜素和白杨素）的抑制活性最强。C环的C-3位无羟基的黄酮类化合物（木犀草素、芹菜素、白杨素）与PLCγ、Lyn、ERK等信号通路有较强的结合能。 【结论】 该研究为开发具有预防和改善AD效果的膳食疗法开辟了新思路。

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.