Abstract
As a rich natural resource for drug discovery, Traditional Chinese Medicine (TCM) plays an important role in complementary and alternative medical systems. TCM shows a daunting complexity of compounds featuring multi-components and multi-targets to cure diseases, which thus always makes it extremely difficult to systematically explain the molecular mechanisms adequately using routine methods. In the present work, to reveal the systematic mechanism of herbal formulae, we developed a pathway-based strategy by combining the pathways integrating, target selection, reverse drug targeting and network analysis together, and then exemplified it by Reduning injection (RDN), a clinically widely used herbal medicine injection, in combating inflammation. The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated. More importantly, our predicted results were also experimentally validated. Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.
Highlights
Traditional Chinese Medicine (TCM) plays an important role in human health through thousands of years of clinical practice [1]
Due to the multi-target drugs that modulate these essential proteins on parallel pathways or similar functional pathways may produce enhanced effect [4,14], these results indicate that Reduning injection (RDN) may enhance the therapeutic efficacy by collective regulation of targets in the signaling networks
MAPK1 and MAPK14 are the hubs with the highest degree of nine, demonstrating that these proteins may act as the major therapeutic targets for RDN, whereas, the downstream targets of the inflammatory pathways have relative lower degrees (e.g. TNF-α with the degree of 3), indicating that RDN cure inflammation mainly through the modulation of these signaling pathways
Summary
Traditional Chinese Medicine (TCM) plays an important role in human health through thousands of years of clinical practice [1]. The molecular mechanisms involved in TCM still remain somewhat unclear. Herbal medicines are normally designed and featured as multicomponent systems that target multi-targets [2], which makes it hard to decipher the mechanisms of action like those single target drugs by traditional pharmacological methods. Systems pharmacology is increasingly gaining acceptance as a promising way to address the complex problems for herbal medicines [3]. We have successfully built an integrated platform of systems pharmacology and applied it into the discovery of PLOS ONE | DOI:10.1371/journal.pone.0123109. We have successfully built an integrated platform of systems pharmacology and applied it into the discovery of PLOS ONE | DOI:10.1371/journal.pone.0123109 April 1, 2015
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