Abstract
Multi-herb therapy has been widely used in Traditional Chinese medicine and tailored to meet the specific needs of each individual. However, the potential molecular or systems mechanisms of them to treat various diseases have not been fully elucidated. To address this question, a systems pharmacology approach, integrating pharmacokinetics, pharmacology and systems biology, is used to comprehensively identify the drug-target and drug-disease networks, exemplified by three representative Radix Salviae Miltiorrhizae herb pairs for treating various diseases (coronary heart disease, dysmenorrheal and nephrotic syndrome). First, the compounds evaluation and the multiple targeting technology screen the active ingredients and identify the specific targets for each herb of three pairs. Second, the herb feature mapping reveals the differences in chemistry and pharmacological synergy between pairs. Third, the constructed compound-target-disease network explains the mechanisms of treatment for various diseases from a systematic level. Finally, experimental verification is taken to confirm our strategy. Our work provides an integrated strategy for revealing the mechanism of synergistic herb pairs, and also a rational way for developing novel drug combinations for treatments of complex diseases.
Highlights
Based on research and experience in the context of multicomponent therapeutics, some experiments in a case-by-case method are usually proposed[5]
In our previous work, we have developed a robust multiple drug-target interactions prediction (DTpre) model to identify the potential targets for a given molecule based on support vector mechanic (SVM) and random forest methods (RF)[23]
These methods only focus on the prediction of drug-target or drug-disease interactions individually, they ignored the concept that Traditional Chinese medicine (TCM) emerged and were considered as a holistic view of the human being which included the integration and dissection of pharmacokinetics profiles, pharmacological features and underlying synergistic mechanisms of action associated with drugs, as well as the investigation of various complex relationships, such as drug-target interactions, drug-disease connections, target-disease associations, drug-pathway connections and from molecular to system level
Summary
Based on research and experience in the context of multicomponent therapeutics, some experiments in a case-by-case method are usually proposed[5]. These methods only focus on the prediction of drug-target or drug-disease interactions individually, they ignored the concept that TCM emerged and were considered as a holistic view of the human being which included the integration and dissection of pharmacokinetics profiles, pharmacological features and underlying synergistic mechanisms of action associated with drugs, as well as the investigation of various complex relationships, such as drug-target interactions, drug-disease connections, target-disease associations, drug-pathway connections and from molecular to system level In comparison with these approaches, systems pharmacology is likely to be a comprehensive method in providing a wealth of information for integrated multi-scale analysis of synergistic mechanisms of multi-component drugs and interrelationships of complex networks by using both computational and experiments techniques[24,25,26]. Knowledge of the molecular mechanism of the synergistic combinations of herb pairs based on systems pharmacology facilitates the development of novel drug combinations that are individually subtherapeutic but efficacious in combination, and opens up new ideas to fundamentally elucidate the scientific connotation of multiple systems of TCM, so as to better explore the complex therapeutic mechanism at the systems level
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