System Analysis of the Synergistic Mechanisms Between Salvia Miltiorrhiza and Panax Notoginseng in Combination
丹参与三七配伍协同分子机制的系统分析

This work adopted systems biology approaches to predict the functional networks for the synergistic mechanisms of the Salvia miltiorrhiza and Panax notoginseng combination. For text mining, TCMGeneDIT was used to retrieve association information regarding genes, Salvia miltiorrhiza and Panax notoginseng; protein-protein interaction information for these genes from databases and Literature data was searched and visualized using Cytoscape; differences between networks were identified by Merge program; highly-connected regions were detected by the IPCA algorithm to infer the significant complexes or pathways in this network; the most relevant functions and pathways were extracted from subnetworks by BiNGO tool. 21 and 41 genes were found to respectively associate with Salvia miltiorrhiza and Panax notoginseng, including 9 genes overlapping both drugs, indicating that 53 genes are associated with drug combination. Protein-protein interaction networks comprised hundreds to thousands of proteins. The subnetworks made up of overlapping proteins between Salvia miltiorrhiza and Panax notoginseng networks were more than the subnetworks reconstituted by protein-protein interaction information concerning the 9 overlapping genes. A new subnetwork emerged by the network about drug combination removed the Salvia miltiorrhiza and Panax notoginseng networks. The most relevant functions and pathways extracted from 4 highly-connected regions in the subnetworks were related to apoptosis, proliferation and small G protein signaling pathways. Taken together, the protocol developed in this study may lead to a deeper understanding of a system as a whole in the mechanism of drug combination and help analyze emergence in a system; Salvia miltiorrhiza and Panax notoginseng combination may have synergistic effects against coronary heart disease in terms of apoptosis, proliferation and small G protein signaling pathways.