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OBJECTIVE:To investigating the molecular mechanism of herbal pairs in three types of Chinese medicinals:Qi-tonifying,blood activation,blood-stasis breaking in treatment of coronary heart disease(CHD).METHODS:The components of six herbs were searched in Chinese medicine dictionary and their target proteins were found in PubChem.CHD genes were obtained from PubMed gene database.Ingenuity Pathways Analysis was used to build the pharmacological network of three herbal pairs and CHD molecular network.The canonical pathways between each herbal pair network and CHD network was compared to decipher the molecular mechanism on three herbal pairs in treating CHD.RESULTS:The network analysis showed that there were the common signal pathways of three herbal pairs in treating CHD including hypoxia signaling in the cardiovascular system,Hypoxia-inducible factor 1-alpha signaling,glucocorticoid receptor signaling,G-Protein coupled receptor signaling and pregnane X receptor/retinoid X receptor (PXR/RXR)activation.Further to analyze cardiovascular signaling,cytokine signaling and cytokine signaling,the effective molecules for three herbal pairs in treating CHD included HIF1a and estrogen receptor 1,Qi-tonifying herbal pair included albumin and matrix metallopeptidase 2,and blood-activation herbal pair included estrogen receptor 2 and peroxisome proliferator-activated receptor-γ.CONCLUSION:Each herbal pair can affect some respective CHD-related functions and pathways,meanwhile three herbal pairs exert some mutual effects on CHD-related functions and pathways.Mutual effects of three herbal pairs may be the key components of their total molecular mechanismsand respective effects of each herbal pair may be the characteristic components of their respective molecular mechanism.