Abstract
BackgroundCompared with the traditional oral administration form, injection administration is basically superior in terms of both biological availability and therapeutic effects. However, few researches have focused on the traditional Chinese medicinal injection due to the complicated constituents and the intricate mechanism of action.MethodsIn the present work, a novel systems pharmacology model, integrating ADME (absorption, distribution, metabolism, and excretion) filtering such as half-life evaluation, network targeting, pathway and systems analyses, is specifically developed for the identification of active compounds and the study of the mechanism of action of TCM injection, which is exemplified by Reduning injection confronting the influenza.ResultsThe ADME filter successfully identifies 35 bioactive compounds (31 molecules and 4 metabolites) from the Reduning injection. The systems analysis and experimental validation further reveal a new way of confronting influenza disease of this injection: 1) stimulating the immunomodulatory agents for immune response activation, and 2) regulating the inflammatory agents for anti-inflammation.ConclusionsThe novel systems pharmacology method used in this study has the potential to advance the understanding of the molecular mechanisms of action of multicomponent herbal injections, and provide clues to discovering more effective drugs against complex diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-430) contains supplementary material, which is available to authorized users.
Highlights
Compared with the traditional oral administration form, injection administration is basically superior in terms of both biological availability and therapeutic effects
The term systems pharmacology describes a field of study that applies the systems biology and PK/PD to provide a quantitative frame-work for understanding the dynamic interplay among variables of complex biological systems through iteration between computational and/or mathematical modelling and experimentation [5,6]
An effective method which is developed for the study of herbal injection is still lacking at the present time
Summary
Chemical database for reduning injection Reduning injection consists of three herbs including Artemisiae annuae L. (genus Artemisia, Asteraceae), Gardenia jasminoides J.Ellis (genus Gardenia, Rubiaceae) and Lonicera japonica Thunb. (genus Lonicera, Caprifoliaceae). Generation of ADME filters To ensure a continuous pipeline of new drugs with reasonable PK, one pivotal activity is the evaluation of ADME parameters for a given compound A total of 169 drugs (injection formulation) with their half-life values, DrugBank ID, chemical name, CAS number were collected from Drugbank database (http://www.drugbank.ca/) [33] (Additional file 2: Table S2). The final score is expressed as an expectation value (E-value), that is, the structural similarity of each drug to each target’s ligand set; and (3) STITCH 4.0 (Search Tool for Interacting Chemicals, http:// stitch.embl.de/), a combined data repository that captures the publicly available knowledge on chemical-protein interactions derived from experiments, expert-curated databases and literature by means of text mining [40]. The level of NO production was monitored by Griess method and according to the indication on the NO assay kit (Beyotime Biotechnology, China)
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