Mechanism Research of Chonglou as a Pain Killer by Network Pharmacology

Objective:The objective of this study is to screen the therapeutic targets of pain of traditional Chinese medicine Chonglou and explore the relevant mechanism by network pharmacology techniques and methods.Materials and Methods:The chemical components of Chonglou were collected according to chemistry database and related literature.SwissADME was used to collect the potential active ingredients from all the chemical components of Chonglou and SwissTarget Prediction was utilized to predict their targets.The genes related to pain were collected from GeneCards and Online Mendelian Inheritance in Man databases.Joint genes were uploaded to the online string database for the analysis and the PPI network was constructed.The"Chonglou-active component-target-pain"network was constructed by Cytoscape 3.7.1 software,Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for key target proteins.The top three active components with most targets in the network were docked with the target proteins by the molecular docking technique.Results:A total of nine potential active compounds of Chonglou,264 potential target genes,2385 targets of pain disorder,and 128 common targets for drug and disease were screened.One hundred and thirty-one GO items were identified by the GO enrichment analysis,and 23 related signaling pathways were identified by the KEGG pathway enrichment analysis.Molecular-docking results show that pennogenin is the optimal butt ligand of PIK3 CA,STAT3,mitogen-activated protein kinase 14,and ADORA1.Conclusion:It is preliminarily revealed that Chonglou might treat pain through multiple targets,multiple biology processes and multiple pain-related signaling pathways,providing reference for the subsequent experimental research.

An Exploration in the Potential Substance Basis and Mechanism of Chuanxiong Rhizoma and Angelicae Dahuricae Radix on Analgesia Based on Network Pharmacology and Molecular Docking

Objective:The objective was to study the potential substance basis and action mechanism of Chuanxiong Rhizoma(CX)and Angelicae Dahuricae Radix(AD)on analgesia through network pharmacology and molecular docking.Materials and Methods:The active components and targets of CX and AD and pain-related genes were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and GeneCards database.Then,the co-action targets were found,protein–protein interaction network was constructed by the String database.The Cytoscape 3.7.1 was used to construct"CX-AD-active components-pain"network.Further enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was carried out to predict its mechanism of action,the top four active components in the network were docked with the targets.Results:There are 26 compounds,45 targets in the network.Among them,(Z)-ligustilide and beta-sitosterol,respectively,have more potential targets in CX and AD,and prostaglandin-endoperoxide synthase(PTGS2),PTGS1 have more ligands.GO analysis shows that molecular functions of CX and AD mainly performed through the G protein-coupled amine receptor activity,adrenergic receptor activity,and catecholamine binding.KEGG analysis indicates that they could exert analgesic effect on the pathways of regulating neuroactive ligand-receptor interaction,serotonergic synapse,and cGMP-PKG signaling pathway.Molecular docking results show that the active compounds are highly compatible with the structure of the protein receptor,and they interact through the hydrogen bond andπ–πbond between the ligand and the active site residues.Conclusions:Through network pharmacology and molecular docking,this study preliminarily revealed the main active components,targets,and potential regulation network of CX and AD,providing a reference for the subsequent experimental research.