Journal
JOURNAL OF ETHNOPHARMACOLOGY
Volume 151, Issue 1, Pages 93-107Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2013.07.001
Keywords
Cardiovascular diseases; Drug discovery and combination; Systems pharmacology; Systems biology
Categories
Funding
- Northwest AF University
- National Natural Science Foundation of China [31170796]
- China Academy of Chinese Medical Sciences [ZZ0608]
- National 973 Program of China [2013CB531805]
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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. (C) 2013 Published by Elsevier Ireland Ltd.
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