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

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 immunom...

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Main Authors: Zhenan Deng, Xuefei Zhang, Junjie Wen, Xiaojing Yang, Lingna Xue, Changxing Ou, Jianjuan Ma, Hongrui Zhan, Xiaomin Cen, Xuliang Cai, Yu Zhang, Riken Chen, Qingling Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1051344/full
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author Zhenan Deng
Xuefei Zhang
Junjie Wen
Xiaojing Yang
Lingna Xue
Changxing Ou
Jianjuan Ma
Hongrui Zhan
Xiaomin Cen
Xuliang Cai
Yu Zhang
Riken Chen
Qingling Zhang
author_facet Zhenan Deng
Xuefei Zhang
Junjie Wen
Xiaojing Yang
Lingna Xue
Changxing Ou
Jianjuan Ma
Hongrui Zhan
Xiaomin Cen
Xuliang Cai
Yu Zhang
Riken Chen
Qingling Zhang
author_sort Zhenan Deng
collection DOAJ
description 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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spelling doaj.art-5e0b768a77ae48208b5337afb0e6b3522022-12-23T07:45:53ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-12-011310.3389/fphar.2022.10513441051344Lonicerin attenuates house dust mite-induced eosinophilic asthma through targeting Src/EGFR signalingZhenan Deng0Xuefei Zhang1Junjie Wen2Xiaojing Yang3Lingna Xue4Changxing Ou5Jianjuan Ma6Hongrui Zhan7Xiaomin Cen8Xuliang Cai9Yu Zhang10Riken Chen11Qingling Zhang12State Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Pediatric Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaDepartment of Rehabilitation, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, ChinaState Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Critical Care Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaEosinophilic 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.1051344/fullasthmaeosinophillonicerinnetwork pharmacologymolecular dockingsrc
spellingShingle Zhenan Deng
Xuefei Zhang
Junjie Wen
Xiaojing Yang
Lingna Xue
Changxing Ou
Jianjuan Ma
Hongrui Zhan
Xiaomin Cen
Xuliang Cai
Yu Zhang
Riken Chen
Qingling Zhang
Lonicerin attenuates house dust mite-induced eosinophilic asthma through targeting Src/EGFR signaling
Frontiers in Pharmacology
asthma
eosinophil
lonicerin
network pharmacology
molecular docking
src
title Lonicerin attenuates house dust mite-induced eosinophilic asthma through targeting Src/EGFR signaling
title_full Lonicerin attenuates house dust mite-induced eosinophilic asthma through targeting Src/EGFR signaling
title_fullStr Lonicerin attenuates house dust mite-induced eosinophilic asthma through targeting Src/EGFR signaling
title_full_unstemmed Lonicerin attenuates house dust mite-induced eosinophilic asthma through targeting Src/EGFR signaling
title_short Lonicerin attenuates house dust mite-induced eosinophilic asthma through targeting Src/EGFR signaling
title_sort lonicerin attenuates house dust mite induced eosinophilic asthma through targeting src egfr signaling
topic asthma
eosinophil
lonicerin
network pharmacology
molecular docking
src
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1051344/full
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