Network analysis of primary active compounds in Danqi analogous formulas for treating cardiovascular disease

Used extensively to treat cardiovascular disease, Danqi analogous formulas (DQAF) include prescriptions for Danqi (DQ), Fufang Danshen (FFDS) and Qishen Yiqi (QSYQ). Differences in prescription compatibility result in varying emphases of DQAF in clinical application.

Based on network analysis in this study, common and distinct mechanisms of DQAF actions on cardiovascular disease were analyzed at a systemic level. Components–targets–pathways models were developed by Cytoscape (http://www.cytoscape.org/); whereby, target information for active compounds was obtained based on the PharmMapper database (http://59.78.96.61/pharmmapper/), which was further used to search pathways using the Kyoto Encyclopedia of Genes and Genomes database (http://www.genome.jp/kegg/). Based on target and network analyses, we discovered RBP4 is a potential common target of DQAF, while mitogen-activated protein kinase 1 (MAPK1) and glutathione S-transferase P were potential targets of FFDS and QSYQ, respectively. Furthermore, the potential of DQAF to treat cardiovascular disease occurs through effects on the endocrine, immune, and digestive systems, in addition to lipid, sugar and amino acid metabolic pathways. Whereas FFDS exhibits effects on Toll-like receptor, transforming growth factor beta and MAPK signaling pathways; QSYQ exerts effects on cyclic adenosine monophosphate signaling, as well as metabolism of glutathione and arachidonic acid.

This study not only reflects the formulas-effect modality of multiple compounds, targets and pathways, but also provides clues to better understand physiological mechanisms of DQAF.