Pathway-pathway network-based study of the therapeutic mechanisms by which salvianolic acid B regulates cardiovascular diseases

Investigation of the potential therapeutic mechanisms of drug candidates is an essential step in the process of new drug discovery. With the rapid development of systems biology, recent network analyses of proteins, drugs, and diseases have enabled great progress in delineating the molecule mechanisms of drug candidates. However, most analyses perform a direct association between gene/protein and disease levels without considering the intermediate biological pathways regulated by the drugs. Given that a protein performs its biological roles through pathways, we propose using a novel pathway-pathway network analysis to investigate the potential therapeutic functions of the drug candidates. Many studies have demonstrated that salvianolic acid B (Sal B) of Salvia miltiorrhiza is an effective therapy for cardiovascular diseases (CVD). Using molecular docking methods to identify direct interacting targets of Sal B, we collected all Sal B-regulated proteins with supporting experimental evidence in PubMed abstracts. FDA-approved CVD drugs and their corresponding targets were also collected. From a traditional drug-protein network analysis, we found that Sal B could affect ACE and REN of the renin-angiotensin-aldosterone system to relax vessels and alleviate hypertension. Subsequent pathway-pathway network analysis was attempted to study the mechanisms of Sal B in treating CVD, and demonstrated that Sal B regulates immunity/inflammation, apoptosis, ion transport and basic metabolism processes in the treatment of CVD. Regulating the immune/inflammation process may be the major mechanism of Sal B. We believe that pathway-pathway network analysis is a novel method for studying the therapeutic mechanisms of herbal ingredients.