A Network Study of Chinese Medicine Xuesaitong Injection to Elucidate a Complex Mode of Action with Multicompound, Multitarget, and Multipathway

Chinese medicine has evolved from thousands of years of empirical applications and experiences of combating diseases. It has become widely recognized that the Chinese medicine acts through complex mechanisms featured as multicompound, multitarget and multipathway. However, there is still a lack of systematic experimental studies to elucidate the mechanisms of Chinese medicine. In this study, the differentially expressed genes (DEGs) were identified from myocardial infarction rat model treated with Xuesaitong Injection (XST), a Chinese medicine consisting of the total saponins from Panax notoginseng (Burk.) F. H. Chen (Chinese Sanqi). A network-based approach was developed to combine DEGs related to cardiovascular diseases (CVD) with lines of evidence from the literature mining to investigate the mechanism of action (MOA) of XST on antimyocardial infarction. A compound-target-pathway network of XST was constructed by connecting compounds to DEGs validated with literature lines of evidence and the pathways that are functionally enriched. Seventy potential targets of XST were identified in this study, of which 32 were experimentally validated either by our in vitro assays or by CVD-related literatures. This study provided for the first time a network view on the complex MOA of antimyocardial infarction through multiple targets and pathways.