Study On The Mechanism Of Effects Of The Combination Of "Key Herbs" In Buzhong Yiqi Decoction On Gastrointestinal Motility Based On Computational Pharmacology

Objective:To explore the mechanism of effects of combination of Cimicifuga foetida and Radix Bupleuri,the “key herbs” in Buzhong Yiqi Decoction,on gastrointestinal motility.Methods: 1.Searching the main active ingredients of Cimicifuga foetida and Radix Bupleuri,the “key herbs” in Buzhong Yiqi Decoction,from Traditional Chinese Medicine Systems Pharmacology Datebase and Analysis Platform(TCMSP)and screening out the compounds with OB≥30% and DL≥ 0.18.2.Using DRAR-CPI server,Gene Cards and OMIM database to predict and screen out the targets for active ingredients of combination of Cimicifuga foetida and Radix Bupleuri to affect gastrointestinal motility and constructing the compound-target network with Cytoscape software.3.Using String database and Cytoscape software to draw a protein-protein interaction(PPI)network.4.Using DAVID database to analyze GO and KEGG pathways for important targets in PPI.5.Using Auto Dock software to verify the molecular docking between ingredients and targets.Results: 1.A total of 34 active ingredients in combination of Cimicifuga foetida and Radix Bupleuri were screened from TCMSP database,including 17 active ingredients in Cimicifuga foetida,16 active ingredients from Radix Bupleuri and 1 active ingredient in both,which may interact with 149 targets.2.A total of 148 possible targets through which the combination of Cimicifuga foetida and Radix Bupleuri would affect gastrointestinal motility were screened out by searching Uniprot database and comparing Gene Cards and OMIM database.3.The Compound-target network contained 20 compounds and 190 corresponding targets and the key targets included Prostaglandin G/H synthase 2,Coagulation factor Xa,and Prostaglandin G/H synthase 1,etc.The PPI network contained 121 proteins and the key proteins were TP53,JUN,TNF,IL-6,and VEGF-A,etc.The active small molecules in combination of Cimicifuga foetida and Radix Bupleuri,such as cimicifugoside,methylcicifugoside_qt and Baicalin 4,combined with the key proteins well.There were 1,126 Gene ontology (GO)items,including 1,012 items related to biological processes concerning regulation of signal transduction and biosynthesis processes as well as regulation of cell metabolism and cell proliferation,etc;87 items related to molecular functions,concerning protein binding,neurotransmitter binding,acetylcholine binding,transcription factor activity,etc;27 items related to cell composition,concerning intracellular organ cavity,extracellular space,plasma membrane,etc.A total of 103 pathways including cancer signaling pathway,focal adhesion signaling pathway,mitogen-activated protein kinase signaling pathway,calcium signaling pathway and Toll-like receptor signaling pathway were screened out with Kyoto Encyclopedia of Genes and Genomes(KEGG).4.The binding activity of the active ingredients of the combination of Cimicifuga foetida and Radix Bupleuri with the important targets was calculated and the results showed that 23 active ingredients had good binding activity and the binding between Cimicifugatin or Baicalin with the important targets was stable.Conclusion: 1.Cimicifuga foetida and Radix Bupleuri can influence gastrointestinal motility by regulating cell metabolism,biosynthesis,signal transduction,cell proliferation and stress response.2.The main compounds of Cimicifuga foetida and Radix Bupleuri would affect gastrointestinal motility through regulating the signaling pathways,such as Pathways in cancer,Calcium signaling pathway,Focal adhesion,MAPK signaling pathway and Toll-like receptor signaling pathway,etc.3.The binding activity of 23 active components of Cimicifuga foetida and Radix Bupleuri with the important targets of TP53,JUN,TNF,IL-6 and VEGF-A is good.