The mechanism of Sanzi Yangqin decoction for asthma treatment based on network pharmacology and experimental verification

Abstract Background Asthma is a chronic airway inflammatory disease characterized by airway inflammation, mucus hypersecretion, airway hyper-reactivity. Sanzi Yangqin Decoction (SZYQD) is widely prescribed for asthma treatment. Its anti-asthma activities have been reported in animal model, but the e...

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Main Authors: Yue Wu, Zhenhua Ni, Shiqiang Wang, Yipeng Sun, Xuming Luo, Xiongbiao Wang, Jinjin Liu
Format: Article
Language:English
Published: BMC 2023-12-01
Series:BMC Complementary Medicine and Therapies
Subjects:
Online Access:https://doi.org/10.1186/s12906-023-04272-6
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author Yue Wu
Zhenhua Ni
Shiqiang Wang
Yipeng Sun
Xuming Luo
Xiongbiao Wang
Jinjin Liu
author_facet Yue Wu
Zhenhua Ni
Shiqiang Wang
Yipeng Sun
Xuming Luo
Xiongbiao Wang
Jinjin Liu
author_sort Yue Wu
collection DOAJ
description Abstract Background Asthma is a chronic airway inflammatory disease characterized by airway inflammation, mucus hypersecretion, airway hyper-reactivity. Sanzi Yangqin Decoction (SZYQD) is widely prescribed for asthma treatment. Its anti-asthma activities have been reported in animal model, but the exact mechanism and targets of SZYQD in asthma treatment have not been fully elucidated. Methods A network pharmacological approach was used to predict the active components, targets, and signalling pathways of SZYQD in asthma, including potential target prediction, protein‒protein interaction (PPI) network construction and analysis, and Gene Ont (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The active ingredients were identified from the SZYQD, and were molecular docked according to the results of network pharmacology. A mouse model of asthma induced by ovalbumin (OVA) and lipopolysaccharide (LPS) was constructed to evaluate the therapeutic effect of SZYQD. Furthermore, the effects of SZYQD and its active ingredients were tested in vitro for regulating inflammation and MUC5AC expression (two main pathophysiologic abnormalities of asthma) in macrophages and airway epithelial cells by using Real-time PCR and western blotting. Results A total of 28 active ingredients and 111 HUB genes were screened in the relevant databases, including three key ingredients (luteolin, β-carotene, and Sinapine) and nine core target genes (JUN, CTNNB1, IL10, TP53, AKT1, STAT3, TNF, IL6 and EGFR). KEGG and GO analysis indicated that the potential anti-asthmatic mechanisms of SZYQD were related to PI3K-Akt signalling pathway and response to lipopolysaccharide, etc. In the in vivo asthmatic model, our findings demonstrated that SZYQD exerted a protective effect against asthmatic mice induced by OVA and LPS through the inhibition of inflammation and mucus overproduction. Consistently, cell experiments showed that the SZYQD extract or the key active ingredients luteolin significantly decreased lipopolysaccharide (LPS)-induced IL-6 expression and activation of the NF-κB pathway in macrophages. In addition, SZYQD extract or luteolin inhibited activation of the AKT pathway and expression of MUC5AC induced by EGF in airway epithelial cells. Conclusion The anti-asthmatic mechanism of SZYQD might be associated with inhibiting inflammation and airway mucus hypersecretion by regulating the NF-κB and AKT signalling pathways as predicted by network pharmacology, which provides more evidence for the application of SZYQD in asthma treatment.
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spelling doaj.art-f361ff746e414661b5a8585858b214ff2023-12-17T12:06:45ZengBMCBMC Complementary Medicine and Therapies2662-76712023-12-0123111410.1186/s12906-023-04272-6The mechanism of Sanzi Yangqin decoction for asthma treatment based on network pharmacology and experimental verificationYue Wu0Zhenhua Ni1Shiqiang Wang2Yipeng Sun3Xuming Luo4Xiongbiao Wang5Jinjin Liu6Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese MedicineAbstract Background Asthma is a chronic airway inflammatory disease characterized by airway inflammation, mucus hypersecretion, airway hyper-reactivity. Sanzi Yangqin Decoction (SZYQD) is widely prescribed for asthma treatment. Its anti-asthma activities have been reported in animal model, but the exact mechanism and targets of SZYQD in asthma treatment have not been fully elucidated. Methods A network pharmacological approach was used to predict the active components, targets, and signalling pathways of SZYQD in asthma, including potential target prediction, protein‒protein interaction (PPI) network construction and analysis, and Gene Ont (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The active ingredients were identified from the SZYQD, and were molecular docked according to the results of network pharmacology. A mouse model of asthma induced by ovalbumin (OVA) and lipopolysaccharide (LPS) was constructed to evaluate the therapeutic effect of SZYQD. Furthermore, the effects of SZYQD and its active ingredients were tested in vitro for regulating inflammation and MUC5AC expression (two main pathophysiologic abnormalities of asthma) in macrophages and airway epithelial cells by using Real-time PCR and western blotting. Results A total of 28 active ingredients and 111 HUB genes were screened in the relevant databases, including three key ingredients (luteolin, β-carotene, and Sinapine) and nine core target genes (JUN, CTNNB1, IL10, TP53, AKT1, STAT3, TNF, IL6 and EGFR). KEGG and GO analysis indicated that the potential anti-asthmatic mechanisms of SZYQD were related to PI3K-Akt signalling pathway and response to lipopolysaccharide, etc. In the in vivo asthmatic model, our findings demonstrated that SZYQD exerted a protective effect against asthmatic mice induced by OVA and LPS through the inhibition of inflammation and mucus overproduction. Consistently, cell experiments showed that the SZYQD extract or the key active ingredients luteolin significantly decreased lipopolysaccharide (LPS)-induced IL-6 expression and activation of the NF-κB pathway in macrophages. In addition, SZYQD extract or luteolin inhibited activation of the AKT pathway and expression of MUC5AC induced by EGF in airway epithelial cells. Conclusion The anti-asthmatic mechanism of SZYQD might be associated with inhibiting inflammation and airway mucus hypersecretion by regulating the NF-κB and AKT signalling pathways as predicted by network pharmacology, which provides more evidence for the application of SZYQD in asthma treatment.https://doi.org/10.1186/s12906-023-04272-6SZYQDAsthmaIL-6AKTNetwork pharmacology
spellingShingle Yue Wu
Zhenhua Ni
Shiqiang Wang
Yipeng Sun
Xuming Luo
Xiongbiao Wang
Jinjin Liu
The mechanism of Sanzi Yangqin decoction for asthma treatment based on network pharmacology and experimental verification
BMC Complementary Medicine and Therapies
SZYQD
Asthma
IL-6
AKT
Network pharmacology
title The mechanism of Sanzi Yangqin decoction for asthma treatment based on network pharmacology and experimental verification
title_full The mechanism of Sanzi Yangqin decoction for asthma treatment based on network pharmacology and experimental verification
title_fullStr The mechanism of Sanzi Yangqin decoction for asthma treatment based on network pharmacology and experimental verification
title_full_unstemmed The mechanism of Sanzi Yangqin decoction for asthma treatment based on network pharmacology and experimental verification
title_short The mechanism of Sanzi Yangqin decoction for asthma treatment based on network pharmacology and experimental verification
title_sort mechanism of sanzi yangqin decoction for asthma treatment based on network pharmacology and experimental verification
topic SZYQD
Asthma
IL-6
AKT
Network pharmacology
url https://doi.org/10.1186/s12906-023-04272-6
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