Establishment pharmacological research platform for "Concurrent treatment of the brain and heart" and its application on dissecting mechanism of Danhong injection / 中国中药杂志

ABSTRACT

The Concurrent treatment of the brain and heart (CTBH) theory is proposed based on traditional Chinese medical theory and clinical practice. In this study, a framework for the pharmacological research platform was established to investigate the principles of concurrent treatment of the brain and heart. The platform for CTBH includes several key techniques for network modeling, discovery of active substances, dissecting mechanism of action and investigation of pharmacokinetic property of TCM. Taking network modeling of CTBH as an example, using database search, literature mining, network construction and module analysis, the that network modules closely associated with the pathological progress of cardiovascular and cerebrovascular diseases were identified, while further functional enrichment analysis of these modules indicated that the key biological processes included oxidative stress, metabolism and inflammation. GSK3B, NOTCH1, CDK4 were identified as key nodes in these network modules. The above-mentioned platform was applied to construct component-biomolecules network of Danhong injection for the identification of common targets and pathways. Among them, GSK3B had the highest correlation with the composition of Danhong injection in the network, and the biological function of whose cluster was related to cell oxidative stress. Based upon results of network analysis, validation experiments suggested that Danhong injection significantly improved the survival rate of oxidative injured myocardial cells and nerve cells, and the protective effect was related to the increase of phosphorylated GSK3β protein expression. Moreover, extracts of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos exerted the synergisticcytoprotective effect. The results indicated that the mechanism of treatment of cardiovascular and cerebrovascular diseases of Danhong injection could be studied through network modeling and other methods. In summary, the proposed pharmacological platform provided a feasible way for revealing the mechanism of CTBH by using modern scientific methods.