Construction And Utilization Of Traditional Chinese Medicine Systems Pharmacology Database And Analysis Platform

Identified as a treasure of natural herbal products, traditional Chinese medicines(TCMs) have attracted extensive attention around the world due to their moderate treatment effects and lower side effects in some complex chronic disorders. However, compared with modern medicine, owing to multi-component and multi-function features in herbal concoctions, the investigations of TCMs in understanding the underlying mechanisms of action of TCM pose big challenges in an understanding of action mechanisms of the herbs in systems-level, which hamper the ‘‘modernization’’ and “globalization’’ of TCMs. Systems pharmacology(SP), an emerging discipline which has drawn an increasing awareness in recent years, opens up a new horizon to address the problems of TCMs investigation. Through computational and/or mathematical modeling and experimentation, it achieves a quantitative analysis of the dynamic interactions between drugs and a biological organism to understand the behavior of the organism in a multi-scale levels which from molecules to networks, cells and organs, and makes it possible to understand the mechanism of the TCM therapy. Based on the methods of systems pharmacology for herbal medicines,the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was built integrating pharmacokinetics and physicochemical properties with a drugs-targets-diseases network, bridging the investigations of modern medicine and traditional medicine for drugs(http://lsp.nwsuaf.edu.cn/tcmsp.php). The database collects all the 500 Chinese herbs registered in the Chinese pharmacopoeia with more than 30,069 ingredients through data mining and database integrating. The pharmacokinetics and physicochemical properties of all the chemical compounds, which consist of compound oral bioavailability(OB), drug-likeness(DL), blood brain barrier(BBB), human colon adenocarcinoma(Caco2) permeability, drug half-life(HL) and Lipinski’s rule of five, were provided for the screening and analysis of the bioactive components. In addition, while the targets and diseases data directly collected from the database of DrugBank, TTD, HIT and so on, the potential target proteins of the active compounds were also identified by constructing the predicted model and collecting the available experimental data. TCMCP is more than a data repository and all the collected data was used to establish the drugs-targets-diseases networks automatically by the tools provided online, which could let users view and further analyze the drug action mechanisms easily. TCMCP, with large number of data, will not only provide the basics to uncover the potential targets and the underlying mechanisms of TCM therapy, but also bring novel approaches for the investigation of TCM.