[Prediction of Pathogenesis and Potential Therapeutic Targets for Asthma Based on Proteomics of Mouse Lung Tissue].

Objective To predict the mechanism and potential therapeutic targets of asthma based on proteomic analysis and network pharmacology.Methods The mouse model of asthma was established via intraperitoneal injection of 200 µl suspension containing 100 µg ovalbumin(OVA)and 2 mg aluminum hydroxide and intranasal administration with 5% OVA.Maxquant system was used to retrieve the protein and gene data.The analysis of variance and t test were performed to obtain differential proteins,and then clustering map and target set of differential proteins were established.The protein-protein interaction network of differential proteins was constructed.The pathogenesis of asthma was investigated via gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Results A total of 5063 genes were identified,from which 904 differentially expressed genes were selected with the thresholds of fold change(model/control)≥2 and P≤0.05 as well as thresholds of fold change(model/control)≤1/2 and P≤0.05.The 904 genes were classified into 3 clusters.The 904 differentially expressed genes included 595 up-regulated genes and 309 down-regulated genes in the model group compared with the control group.The pathogenesis of asthma was associated with regulatory metabolism,Fc gamma-R mediated phagocytosis,leukocyte transendothelial migration,tumor necrosis factor signaling pathway,Toll-like receptor signaling pathway,B cell receptor signaling pathway,phosphoinositol 3-kinase/protein kinase B signaling pathway,vascular smooth muscle contraction and cell adhesion signaling pathway.ITGB3,CYBB,SYK,VWF,ITGB2,MYD88,COMP,VEGFA,and FCGR2B were identified as the therapeutic targets for asthma.Meanwhile,the biological processes such as signal transduction,redox process,immune response,inflammatory response,cell adhesion,positive regulation of GTPase activity,apoptosis,and extracellular matrix formation were the main participants in asthma.Conclusion This study systematically revealed the pathogenesis,biological processes,and 9 potential therapeutic targets of asthma.

A Systems Pharmacology Approach for Identifying the Multiple Mechanisms of Action for the Rougui-Fuzi Herb Pair in the Treatment of Cardiocerebral Vascular Diseases.

Cardiocerebral vascular diseases (CCVDs) are the main reasons for high morbidity and mortality all over the world, including atherosclerosis, hypertension, myocardial infarction, stroke, and so on. Chinese herbs pair of the Cinnamomum cassia Presl (Chinese name, rougui) and the Aconitum carmichaelii Debx (Chinese name, fuzi) can be effective in CCVDs, which is recorded in the ancient classic book Shennong Bencao Jing, Mingyibielu and Thousand Golden Prescriptions. However, the active ingredients and the molecular mechanisms of rougui-fuzi in treatment of CCVDs are still unclear. This study was designed to apply a system pharmacology approach to reveal the molecular mechanisms of the rougui-fuzi anti-CCVDs. The 163 candidate compounds were retrieved from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). And 84 potential active compounds and the corresponding 42 targets were obtained from systematic model. The underlying mechanisms of the therapeutic effect for rougui-fuzi were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, component-target-disease (C-T-D) and target-pathway (T-P) networks were constructed to further dissect the core pathways, potential targets, and active compounds in treatment of CCVDs for rougui-fuzi. We also constituted protein-protein in interaction (PPI) network by the reflect target protein of the crucial pathways against CCVDs. As a result, 21 key compounds, 8 key targets, and 3 key pathways were obtained for rougui-fuzi. Afterwards, molecular docking was performed to validate the reliability of the interactions between some compounds and their corresponding targets. Finally, UPLC-Q-Exactive-MSE and GC-MS/MS were analyzed to detect the active ingredients of rougui-fuzi. Our results may provide a new approach to clarify the molecular mechanisms of Chinese herb pair in treatment with CCVDs at a systematic level.