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Objective: To predict the action targets of anti-acute lung injury active ingredients of Xuebijing Injection, and investigate the “multi-components, multi-targets, and multi-pathways” mechanism. Methods: Reverse molecular docking was used to forecast its targets of 38 main active components of Xuebijing Injection. The relevant targets of acute lung injury were searched through literature mining and multiple databases and compared with the predicted component targets. The protein interaction network was constructed by Cytoscape software, and topological analysis was performed to screen the key targets of anti-acute lung injury of Xuebijing Injection. And GO enrichment analysis and KEGG analysis were carried out on the key targets through DAVID database. Results: The network analysis indicated that 38 active ingredients affected 143 key target proteins directly or indirectly, involved in 71 biological processes, 29 cellular components, 40 molecular function, and 25 KEGG pathways. These active compounds might participate in regulating the processes of gene, protein, external stimulus, and interfering the mitogen-activated protein kinase (MAPK), phosphatidyl inositol 3-kinase (PI3K)-Akt, and other signaling pathways to play a role in resisting to acute lung injury. Conclusion: The anti-acute lung injury effect of Xuebijing Injection showed the characteristics of traditional Chinese medicine in multi-components, multi-targets, and multi-pathways. This research provides a scientific basis for elucidation of the anti-acute lung injury pharmacological mechanism of Xuebijing Injection.
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Objective A “Compound-Target-Pathway-Disease” network of the anticancer effect of ailanthone was built through reverse molecular docking and network pharmacological technology to explore the underlying mechanism. Methods Ailanthone was submitted to PharmMapper and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatics software to predict the target proteins and related pathways respectively. The network of “Compound-Target-Pathway-Disease” was constructed and analyzed by using Cytoscape software. Results Data analysis showed that there were 102 potential targets of ailanthone for human target proteins, and 17 pathways are associated with tumors. Ailanthone played an anticancer role by acting MAP2K1, PI3KR1, EGFR, GRB2, MDM2, MET and other target genes, respectively. Among them, 18, 14, and 11 target genes were respectively enriched in pathways in cancer, proteoglycans cancer and prostate cancer pathway, and six target protein genes were enriched separately in the glioma, melanoma, endometrial cancer and non-small cell lung cancer pathways through regulating signaling pathways such as Cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, and PPAR signaling pathway. Conclusion Research suggests that ailanthone can be considered as a promising new potential drug for the treatment of some cancers such as prostate cancer, non-small cell lung cancer, glioma and melanoma, which also provides theoretical support for the research on the target of ailanthone in the treatment of cancer, pharmacological activity and clinical application.
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OBJECTIVE To construct a network of active components-effect target of xiangdan injection and the network of protein interaction,to analyze the functions and pathways involved in the targets,and to investigate its mechanism of multicomponent-multitarget-multipathway in the treatment of coronary heart disease. METHODS The main active components in xiangdan injection, such as danshensu, salvianolic acid A, salvianolic acid B, salvianolic acid D, tanshinone ⅡA, protocatechuic aldehyde,rosmarinic acid,and oxidated nerolidol were used as the research object to predict targets of active components in xiangdan injection on the basis of reverse docking server (PharmMapper),to screen the targets for the treatment of coronary heart disease through the human genome annotation database (GeneCards), to construct active ingredients-target disease network using Cytoscape 3.5.1 software, to construct target protein protein interaction(PPI) network using STRING platform,and to analyze the target GO biological process and KEGG metabolic pathway using biological information annotation database (DAVID). RESULTS Eight pharmacodynamic components of xiangdan injection act on ACE, HSP90AA1, AKT1, NOS3, F2, F7 and other 257 potential targets for coronary heart disease,which mainly related to the 13 signaling pathways and 12 biological processes. CONCLUSION The main active ingredient of xiangdan injection could treat the coronary heart disease by PPAR, complement and coagulation cascades, HIF-1, estrogen signaling pathway, play a role of anti-inflammatory, anticoagulant, anti-hypoxia, anti-apoptosis and regulating hormones.
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Objective: To predict the action targets of antidepressant active ingredients of Jiaotai Pills to understand the "multi-components, multi-targets, and multi-pathways" mechanism. Methods: ADME/T calculation method was used to filtrate the active components of Jiaotai Pills, and then forecast the targets of the main active ingredients according to Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), reverse molecular docking database (DRAR-CPI), and text mining tools (CooLGeN). Besides, the Gephi software was used to construct Jiaotai Pills ingredients-targets network, while Biological information annotation databases (DAVID) was used to analyze the molecular function and biological process of the action targets. Results: The network analysis indicated that total 28 active ingredients and their 38 targets were screened in Jiaotai Pills, which involved in regulation of actin cytoskeleton, MAPK signaling pathway, neurotrophin signaling pathway, Wnt signaling pathway, axon guidance, and ErbB signaling pathway. The antidepressant effect of Jiaotai Pills showed the features of traditional Chinese medicine in multi-components, multi-targets, and multi-pathways. Conclusion: This study provides new clues for further basic study on the antidepressant pharmacological mechanism of Jiaotai Pills.
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OBJECTIVE:To study the potential targets of Guizhi decoction regulating Ying and Wei based oncorrespondence between formulation and syndromerelationship and reverse molecular docking technology. METHODS:Active ingredients related to Guizhi decoction were obtained by literature retrievals,and PharmMapper Server was used for reverse molecular docking for ac-tive ingredients. The potential receptors of Guizhi decoction were found on the basis of docking scores,then AutoDock Vina was conducted for positive molecular docking test to observe the affinity between the ligand and the receptor molecule. 75 rats were ran-domly divided into normal group,model group,Guizhi decoction high-dose,medium-dose,low-dose groups(12,8,4 g/kg),15 in each group. Except for normal group,rats in other groups were induced for models with disharmony between Ying and Wei. Af-ter modeling,rats were intragastrically administrated once a day,for 5 d. After administration,11β-HSD1 expression levels in adi-pose tissue and muscle tissue of rats were detected. RESULTS:Reverse molecular docking for active ingredients of Guizhi decoc-tion found that 11β-HSD1 was the frequent receptor,and positive docking test confirmed that uralsaponin b,glycyrrhetnic acid and carbenoxolone and so on had higher affinity with 11β-HSD1. Results of animal test showed,compared with normal group,11β-HSD1 expression levels in adipose tissue and muscle tissue in model group were increased (P<0.05);and compared with model group,11β-HSD1 expression levels in adipose tissue and muscle tissue in Guizhi decoction high-dose group were decreased (P<0.05). CONCLUSIONS:Guizhi decoction regulating Ying and Wei has certain correlation with 11β-HSD1,while the reverse molec-ular docking technology can provide a feasible technical way to studycorrespondence between formulation and syndromerelation-ship.
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Traditional Chinese medicine(TCM) modernization has gradually become a worldwide trend. Reverse docking technology has also gradually become a useful tool for TCM modernization. It involves docking a small-molecule drug in the potential binding cavities of a set of clinically relevant macromolecular targets. Detailed analysis of the binding characteristics was used for the ranking of the targets according to the tightness of binding. This process can be used to potentially identify the novel molecular targets for the drug which may be relevant to its mechanism of action or side effect. In order to explore the action mechanism, screen the active ingredients and seek the treating target of TCM, reverse molecular docking technology has been widely used and has achieved remarkable results in recent years. In this review, we summarized the application of reverse molecular docking technology in the target seeking, active ingredients screening and potential mechanism exploration of TCM, which may provide more scientific basis for the clinical research and development of new herbal drugs.
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This study was designed to explore the mechanism of Yuanhu Zhitong Dropping Pills (YHZT) in the treatment of primary dysmenorrhea by pharmacological network technology and establish a research approach of "Compound-Target-Pathway-Disease" network. Twenty-eight compounds absorbed into blood including 22 prototype and 6 metabolites of YHZT were submitted to PharmMapper and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatics softwares to predict the target proteins and related pathways respectively. The network of "Compound-Target-Pathway-Disease" was constructed and analyzed using Cytoscape software. The in silico prediction results showed that the 28 constituents of YHZT affected 111 pathways through 109 target proteins. Among them, a total of 52 proteins and 31 pathways were related to the primary dysmenorrhea. The effect of YHZT on primary dysmenorrhea may be dependent on regulation of the proteins and pathways related with hormonal regulation, central analgesia, spasmolysis, inflammation and immunoregulation.