An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric Pneumonia
Xiebai San (XBS) is a traditional Chinese medicine (TCM) prescription that has been widely used to treat pediatric pneumonia since the Song dynasty. To reveal its underlying working mechanism, a network pharmacology approach was used to predict the active ingredients and potential targets of XBS in...
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.784729/full |
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| author | Zhuohui Luo Zhuohui Luo Jiawen Huang Ennian Li Xinqian He Qiqi Meng Xinan Huang Xiaoling Shen Changkai Yan |
| author_facet | Zhuohui Luo Zhuohui Luo Jiawen Huang Ennian Li Xinqian He Qiqi Meng Xinan Huang Xiaoling Shen Changkai Yan |
| author_sort | Zhuohui Luo |
| collection | DOAJ |
| description | Xiebai San (XBS) is a traditional Chinese medicine (TCM) prescription that has been widely used to treat pediatric pneumonia since the Song dynasty. To reveal its underlying working mechanism, a network pharmacology approach was used to predict the active ingredients and potential targets of XBS in treating pediatric pneumonia. As a result, 120 active ingredients of XBS and 128 potential targets were screened out. Among them, quercetin, kaempferol, naringenin, licochalcone A and isorhamnetin showed to be the most potential ingredients, while AKT1, MAPK3, VEGFA, TP53, JUN, PTGS2, CASP3, MAPK8 and NF-κB p65 showed to be the most potential targets. IL-17 signaling pathway, TNF signaling pathway and PI3K-Akt signaling pathway, which are involved in anti-inflammation processes, immune responses and apoptosis, showed to be the most probable pathways regulated by XBS. UPLC-Q/Orbitrap HRMS analysis was then performed to explore the main components of XBS, and liquiritin, quercetin, kaempferol, licochalcone A and glycyrrhetinic acid were identified. Molecular docking analysis of the compounds to inflammation-associated targets revealed good binding abilities of quercetin, kaempferol, licochalcone A and liquiritin to NF-κB p65 and of quercetin and kaempferol to Akt1 or Caspase-3. Moreover, molecular dynamics (MD) simulation for binding of quercetin or kaempferol to NF-κB p65 revealed dynamic properties of high stability, high flexibility and lowbinding free energy. In the experiment with macrophages, XBS markedly suppressed the (Lipopolysaccharides) LPS-induced expression of NF-κB p65 and the production of pro-inflammatory cytokines IL-6 and IL-1β, supporting XBS to achieve an anti-inflammatory effect through regulating NF-κB p65. XBS also down-regulated the expression of p-Akt (Ser473)/Akt, Bax and Caspase-3 and up-regulated the expression of Bcl-2, indicating that regulating Akt1 and Caspase-3 to achieve anti-apoptotic effect is also the mechanism of XBS for treating pediatric pneumonia. Our study helped to reveal the pharmacodynamics material basis as well as the mechanism of XBS in treating pediatric pneumonia. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-24T00:23:18Z |
| publishDate | 2022-02-01 |
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| spelling | doaj.art-dfe6fb04c2d74a70a24cf68ee7c246812022-12-21T17:24:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-02-011310.3389/fphar.2022.784729784729An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric PneumoniaZhuohui Luo0Zhuohui Luo1Jiawen Huang2Ennian Li3Xinqian He4Qiqi Meng5Xinan Huang6Xiaoling Shen7Changkai Yan8Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaHonz Pharmaceutical Co., Ltd., Haikou, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaArtemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaArtemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaHonz Pharmaceutical Co., Ltd., Haikou, ChinaXiebai San (XBS) is a traditional Chinese medicine (TCM) prescription that has been widely used to treat pediatric pneumonia since the Song dynasty. To reveal its underlying working mechanism, a network pharmacology approach was used to predict the active ingredients and potential targets of XBS in treating pediatric pneumonia. As a result, 120 active ingredients of XBS and 128 potential targets were screened out. Among them, quercetin, kaempferol, naringenin, licochalcone A and isorhamnetin showed to be the most potential ingredients, while AKT1, MAPK3, VEGFA, TP53, JUN, PTGS2, CASP3, MAPK8 and NF-κB p65 showed to be the most potential targets. IL-17 signaling pathway, TNF signaling pathway and PI3K-Akt signaling pathway, which are involved in anti-inflammation processes, immune responses and apoptosis, showed to be the most probable pathways regulated by XBS. UPLC-Q/Orbitrap HRMS analysis was then performed to explore the main components of XBS, and liquiritin, quercetin, kaempferol, licochalcone A and glycyrrhetinic acid were identified. Molecular docking analysis of the compounds to inflammation-associated targets revealed good binding abilities of quercetin, kaempferol, licochalcone A and liquiritin to NF-κB p65 and of quercetin and kaempferol to Akt1 or Caspase-3. Moreover, molecular dynamics (MD) simulation for binding of quercetin or kaempferol to NF-κB p65 revealed dynamic properties of high stability, high flexibility and lowbinding free energy. In the experiment with macrophages, XBS markedly suppressed the (Lipopolysaccharides) LPS-induced expression of NF-κB p65 and the production of pro-inflammatory cytokines IL-6 and IL-1β, supporting XBS to achieve an anti-inflammatory effect through regulating NF-κB p65. XBS also down-regulated the expression of p-Akt (Ser473)/Akt, Bax and Caspase-3 and up-regulated the expression of Bcl-2, indicating that regulating Akt1 and Caspase-3 to achieve anti-apoptotic effect is also the mechanism of XBS for treating pediatric pneumonia. Our study helped to reveal the pharmacodynamics material basis as well as the mechanism of XBS in treating pediatric pneumonia.https://www.frontiersin.org/articles/10.3389/fphar.2022.784729/fullnetwork pharmacologymolecular dockingmolecular dynamics simulationexperiment verificationXiebai Sanpediatric pneumonia |
| spellingShingle | Zhuohui Luo Zhuohui Luo Jiawen Huang Ennian Li Xinqian He Qiqi Meng Xinan Huang Xiaoling Shen Changkai Yan An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric Pneumonia Frontiers in Pharmacology network pharmacology molecular docking molecular dynamics simulation experiment verification Xiebai San pediatric pneumonia |
| title | An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric Pneumonia |
| title_full | An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric Pneumonia |
| title_fullStr | An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric Pneumonia |
| title_full_unstemmed | An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric Pneumonia |
| title_short | An Integrated Pharmacology-Based Strategy to Investigate the Potential Mechanism of Xiebai San in Treating Pediatric Pneumonia |
| title_sort | integrated pharmacology based strategy to investigate the potential mechanism of xiebai san in treating pediatric pneumonia |
| topic | network pharmacology molecular docking molecular dynamics simulation experiment verification Xiebai San pediatric pneumonia |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.784729/full |
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