Objective: Qingfei Tongluo Plaster(QFP), an improved Chinese medicine hospital preparation, is an attractive treatment option due to its well clinical efficacy, convenience, economy, and patient compliance in the trea...Objective: Qingfei Tongluo Plaster(QFP), an improved Chinese medicine hospital preparation, is an attractive treatment option due to its well clinical efficacy, convenience, economy, and patient compliance in the treatment of respiratory syncytial virus(RSV) pneumonia. The aim of this study was to investigate the efficacy mechanism of QFP on RSV rats from the perspective of alleviating lung inflammation and further explore the changes of serum metabolites and metabolic pathways in RSV rats under the influence of QFP.Methods: This study used network pharmacological methods and molecular docking combined with molecular biology and metabolomics from multi-dimensional perspectives to screen and verify the therapeutic targets. Open online databases were used to speculate the gene targets of efficient ingredients and diseases. Then, we used the String database to examine the fundamental interaction of common targets of drugs and diseases. An online enrichment analysis was performed to predict the functional pathways. Molecular docking was applied to discover the binding modes between essential ingredients and crucial gene targets. Finally, we demonstrated the anti-inflammatory ability of QFP in the RSV-evoked pneumonia rat model and explained the mechanism in combination with the metabolomics results.Results: There were 19 critical targets defined as the core targets: tumor necrosis factor(TNF), inducible nitric oxide synthase 2(NOS2), mitogen-activated protein kinase 14(MAPK14), g1/S-specific cyclin-D1(CCND1), signal transducer and activator of transcription 1-alpha/beta(STAT1), proto-oncogene tyrosine-protein kinase Src(SRC), cellular tumor antigen p53(TP53), interleukin-6(IL6), hypoxiainducible factor 1-alpha(HIF1A), RAC-alpha serine/threonine-protein kinase(AKT1), signal transducer and activator of transcription 3(STAT3), heat shock protein HSP 90-alpha(HSP90AA1), tyrosine-protein kinase JAK2(JAK2), cyclin-dependent kinase inhibitor 1(CDKN1A), mitogen-activated protein kinase 3(MAPK3), epidermal growth factor receptor(EGFR), myc proto-oncogene protein(MYC), protein c-Fos(FOS) and transcription factor p65(RELA). QFP treated RSV pneumonia mainly through the phosphatidylinositol 3-kinase(PI3K)/RAC AKT pathway, HIF-1 pathway, IL-17 pathway, TNF pathway, and MAPK pathway. Animal experiments proved that QFP could effectively ameliorate RSV-induced pulmonary inflammation. A total of 28 metabolites underwent significant changes in the QFP treatment, and there are four metabolic pathways consistent with the KEGG pathway analyzed by network pharmacology,suggesting that they may be critical processes related to treatment.Conclusion: These results provide essential perspicacity into the mechanisms of action of QFP as a promising anti-RSV drug.展开更多
基金supported by the National Natural Science Foundation of China (No. 81973906)。
文摘Objective: Qingfei Tongluo Plaster(QFP), an improved Chinese medicine hospital preparation, is an attractive treatment option due to its well clinical efficacy, convenience, economy, and patient compliance in the treatment of respiratory syncytial virus(RSV) pneumonia. The aim of this study was to investigate the efficacy mechanism of QFP on RSV rats from the perspective of alleviating lung inflammation and further explore the changes of serum metabolites and metabolic pathways in RSV rats under the influence of QFP.Methods: This study used network pharmacological methods and molecular docking combined with molecular biology and metabolomics from multi-dimensional perspectives to screen and verify the therapeutic targets. Open online databases were used to speculate the gene targets of efficient ingredients and diseases. Then, we used the String database to examine the fundamental interaction of common targets of drugs and diseases. An online enrichment analysis was performed to predict the functional pathways. Molecular docking was applied to discover the binding modes between essential ingredients and crucial gene targets. Finally, we demonstrated the anti-inflammatory ability of QFP in the RSV-evoked pneumonia rat model and explained the mechanism in combination with the metabolomics results.Results: There were 19 critical targets defined as the core targets: tumor necrosis factor(TNF), inducible nitric oxide synthase 2(NOS2), mitogen-activated protein kinase 14(MAPK14), g1/S-specific cyclin-D1(CCND1), signal transducer and activator of transcription 1-alpha/beta(STAT1), proto-oncogene tyrosine-protein kinase Src(SRC), cellular tumor antigen p53(TP53), interleukin-6(IL6), hypoxiainducible factor 1-alpha(HIF1A), RAC-alpha serine/threonine-protein kinase(AKT1), signal transducer and activator of transcription 3(STAT3), heat shock protein HSP 90-alpha(HSP90AA1), tyrosine-protein kinase JAK2(JAK2), cyclin-dependent kinase inhibitor 1(CDKN1A), mitogen-activated protein kinase 3(MAPK3), epidermal growth factor receptor(EGFR), myc proto-oncogene protein(MYC), protein c-Fos(FOS) and transcription factor p65(RELA). QFP treated RSV pneumonia mainly through the phosphatidylinositol 3-kinase(PI3K)/RAC AKT pathway, HIF-1 pathway, IL-17 pathway, TNF pathway, and MAPK pathway. Animal experiments proved that QFP could effectively ameliorate RSV-induced pulmonary inflammation. A total of 28 metabolites underwent significant changes in the QFP treatment, and there are four metabolic pathways consistent with the KEGG pathway analyzed by network pharmacology,suggesting that they may be critical processes related to treatment.Conclusion: These results provide essential perspicacity into the mechanisms of action of QFP as a promising anti-RSV drug.
