7,4'-Dihydroxyflavone ,an orally active flavonoid isolated from Glycyrrhiza uralensis (licorice), functions as an inhibitor of eotaxin/CCL11 and carbonyl reductase 1 (CBR1) [1]. It persistently suppresses eotaxin production and prevents the rebound effect of dexamethasone (Dex) on eotaxin generation [2]. Furthermore,7,4'-Dihydroxyflavone inhibits MUC5AC gene expression, mucus production, and secretion by modulating the NF-κB, STAT6, and HDAC2 signaling pathways[3].
In human lung fibroblast-1 cells, 7,4'-Dihydroxyflavone (10μM; 24-72h) inhibited the enhancement of p-STAT6 in Dex LT culture and suppressed the expression of HDAC2. [2]. In NCI-H292 cells, 10µM of 7,4'-Dihydroxyflavone significantly inhibited PMA-induced MUC5AC production [3].
In an ovalbumin-sensitized/challenged mouse model, 7,4'-dihydroxyflavone inhibited MUC5AC secretion in vivo. Treatment with 6µg/mL of 7,4'-dihydroxyflavone for 4 weeks significantly reduced the levels of MUC5AC protein in the bronchoalveolar lavage fluid (BAL) of ovalbumin-sensitized/challenged mice [3].
References:
[1]. Liu C, Yang N, Robalino R P, et al. 7, 4'-Dihydroxyflavone isolated from Glycyrrhiza uralensis a constituent of ASHMITM prevents dexamethasone enhancement of Eotaxin-1 secretion by human lung fibroblasts[J]. Journal of Allergy and Clinical Immunology, 2014, 133(2): AB142.
[2]. Liu ChangDa L C D, Yang Nan Y N, Chen XiaoKe C X K, et al. The flavonoid 7, 4′-dihydroxyflavone prevents dexamethasone paradoxical adverse effect on eotaxin production by human fibroblasts[J]. 2017.
[3]. Liu C, Weir D, Chakrapani S, et al. The Flavonoid 7, 4'-Dihydroxyflavone Inhibits Human Airway Epithelial Cells MUC5AC Mucin Production Via Regulation of NF-êb, STAT6 and HDAC2[J]. Journal
7,4'-Dihydroxyflavone是一种从甘草（Glycyrrhiza uralensis）中分离得到的口服活性黄酮类化合物，可作为嗜酸性粒细胞趋化因子/CCL11和羰基还原酶1（CBR1）的抑制剂[1]。7,4'-Dihydroxyflavone可以持续抑制嗜酸性粒细胞趋化因子的产生，并阻止地塞米松（Dex）对嗜酸性粒细胞趋化因子产生的反弹效应[2]。此外，7,4'-Dihydroxyflavone通过调节NF-κB、STAT6和HDAC2信号通路，抑制MUC5AC基因表达、黏液生成和分泌[3]。
在人肺成纤维细胞-1细胞中，7,4'-Dihydroxyflavone（10μM；24-72h）抑制了地塞米松培养中p-STAT6的升高，并抑制了HDAC2的表达[2]。在NCI-H292细胞中，10μM的7,4'-Dihydroxyflavone显著抑制了PMA诱导的MUC5AC产生[3]。
在卵清蛋白致敏/激发的小鼠模型中，7,4'-二羟基黄酮可抑制体内MUC5AC的分泌。用6µg/mL的7,4'-Dihydroxyflavone治疗4周后，卵清蛋白致敏/激发小鼠支气管肺泡灌洗液（BAL）中MUC5AC蛋白的水平显著降低[]。