Systems pharmacology strategies for drug discovery and combination with applications to cardiovascular diseases

Abstract Ethnopharmacological relevance Multi-target therapeutics is a promising paradigm for drug discovery which is expected to produce greater levels of efficacy with fewer adverse effects and toxicity than monotherapies. Medical herbs featuring multi-components and multi-targets may serve as valuable resources for network-based multi-target drug discovery. Materials and methods In this study, we report an integrated systems pharmacology platform for drug discovery and combination, with a typical example applied to herbal medicines in the treatment of cardiovascular diseases. Results First, a disease-specific drug–target network was constructed and examined at systems level to capture the key disease-relevant biology for discovery of multi-targeted agents. Second, considering an integration of disease complexity and multilevel connectivity, a comprehensive database of literature-reported associations, chemicals and pharmacology for herbal medicines was designed. Third, a large-scale systematic analysis combining pharmacokinetics, chemogenomics, pharmacology and systems biology data through computational methods was performed and validated experimentally, which results in a superior output of information for systematic drug design strategies for complex diseases. Conclusions This strategy integrating different types of technologies is expected to help create new opportunities for drug discovery and combination.