Serum Pharmacochemistry And Metabolomic Studies Of Compound Danshen Tablets

Compound Danshen Tablets (CDTs), an herbal compound preparation consisting of Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum, which was officially recorded in the 2005's edition of Chinese pharmacopoeia, holding the functions of promoting blood circulation and removing blood stasis and regulating qi-flowing to relieve pain. It has been wildly used for the treatment of cardiovascular diseases (myocardial infarction, coronary heart disease…) via decreasing blood lipids and inhibiting thrombosis since 1970s. However, mechanisms of action of CDTs are not completely understood. In addition, there are many chemical compositions in the formula, what is important, not all the compounds are active components. During the last years, the study of Chinese medicine was limited for the lack of effective methodology. In our study, we aimed to find the active components of CDTs and explore mechanisms of action of CDTs.As we known, formulas play complex therapeutic effects through roles of multi-component on multi-target under special conditions. The efficacy of Chinese medicine attaches great importance to systematic and holistic actions. Therefore, the study of active components mechanism of Chinese medicine should start with a whole. Among the various methods, the serum pharmacochemistry and metabolomics studies are very holistic, which happens to coincide with Chinese medicine as a whole concept. Serum pharmacochemistry study aimed to explore the active components of drugs by analyzing the serum after administration to explain the whole process of drugs in vivo; metabolomics approach aimed to judge the state of body's metabolic network by analyzing endogenous metabolites to diagnose diseases and study mechanisms of action of drugs.Based on theories of serum pharmacochemistry and metabolomics, with the help of advanced LC-MS and other modern analytical techniques, we carried out the study of pharmacodynamic material basis of CDTs and investigation of mechanisms of action for the treatment of myocardial ischemia through the animal experiment. The main content is as follows:(1) Based on serum pharmacochemistry theory, RRLC-Q-TOF/MS analysis method was established to detect components and metabolites of CDTs in rat serum after administration, which meaned to discover novel compounds in dosed rat serum by comparing the metabolic fingerprinting between the control and dosed groups.(2) Based on metabolomics theory, UPLC-Q-TOF/MS analysis method was established to explore the biomarkers of myocardial ischemic, which meaned to detect and identify significant changed metabolites by comparing the metabolic fingerprinting between the sham and myocardial ischemic model groups.(3) Based on the results of metabolomic study, we further studied the protections of five western medicines with different mechanismes of action (Verapamil, Captopril, Propranolol,Isosorbide Dinitrate and Trimetazidine) and Chinese medicines (CDTs and its active components). Finally, mechanisms of CDTs and its active components (TanshinoneIIA and Salvianolic acid B) for the treatment of myocardial ischemia were explained by comparison with western medicines.In summary, 14 components and 8 metabolites of CDTs were detected in dosed rat serum; 22 metabolites were identified as the biomarkers of myocardial ischemia; after comparative study of Chinese medicine and western medicine, CDTs has unique characteristics for the treatment of myocardial ischemia, TanshinoneIIA is a calcium antagonist and Salvianolic acid B is a beta-adrenergic blocker.