Lonicerin attenuates house dust mite-induced eosinophilic asthma through targeting Src/EGFR signaling

被引:11
作者
Deng, Zhenan [1 ]
Zhang, Xuefei [2 ]
Wen, Junjie [1 ]
Yang, Xiaojing [1 ]
Xue, Lingna [1 ]
Ou, Changxing [1 ]
Ma, Jianjuan [3 ]
Zhan, Hongrui [4 ]
Cen, Xiaomin [1 ]
Cai, Xuliang [1 ]
Zhang, Yu [5 ]
Chen, Riken [1 ]
Zhang, Qingling [1 ]
机构
[1] Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, Natl Ctr Resp Med,Affiliated Hosp 5,Dept Pulm & Cr, Guangzhou, Peoples R China
[2] Southern Med Univ, Zhujiang Hosp, Dept Rehabil Med, Guangzhou, Peoples R China
[3] Guizhou Med Univ, Dept Pediat Hematol, Affiliated Hosp, Guiyang, Peoples R China
[4] Sun Yat Sen Univ, Dept Rehabil, Affiliated Hosp 5, Zhuhai, Peoples R China
[5] Guangzhou Med Univ, Dept Crit Care Med, Affiliated Hosp 5, Guangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
asthma; eosinophil; lonicerin; network pharmacology; molecular docking; src; EGFR; EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; PHARMACOLOGY; INFLAMMATION; EXPRESSION; INHIBITOR; JAPONICA;
D O I
10.3389/fphar.2022.1051344
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Eosinophilic asthma is the predominant phenotype of asthma, and although these patients are sensitive to glucocorticoid therapy, they also experience many side effects. Lonicerin is a kind of bioflavonoid isolated from the Chinese herb Lonicera japonica Thunb, which has anti-inflammatory and immunomodulatory effects. The aim of this study was to elucidate the effects of lonicerin on eosinophilic asthma and its potential mechanisms. Here, we established a house dust mite (house dust mite)-induced eosinophilic asthma model in BALB/c mouse, and evaluated the effects of lonicerin on it. Our results showed that lonicerin significantly reduced airway hyperresponsiveness the number of inflammatory cells (especially eosinophils) and the elevation of interleukin (IL)-4, IL-5, IL-13 and eotaxin in bronchoalveolar lavage fluid (BALF) supernatants of mice. Additionally, lonicerin also eminently blunted inflammatory infiltration and mucus secretion, as well as mRNA levels of Mucin 5AC (MUC5AC) in lung tissue. Furthermore, results of network pharmacology and molecular docking revealed that Src kinase and epidermal growth factor receptor may be the potential targets responsible for the effects of lonicerin. Finally, in vivo experiments confirmed that lonicerin inhibited activation of the Src/EGFR pathway by decreasing their phosphorylation. Taken together, the present study demonstrated that lonicerin could suppress HDM-induced eosinophilic asthma in mice through inhibiting the activation of Src/EGFR pathway, which also provides a basis for further research as a new potentially therapeutic agent for eosinophilic asthma and its underlying mechanisms in the future.
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页数:14
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