A novel systems pharmacology model for herbal medicine injection: a case using reduning injection

Background: Compared 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. Methods: In 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. Results: The 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. Conclusions: The 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.