Pharmacological network-based study on interventional mechanism of Gu-Chang-Zhi-Xie pills for treatment of irritable bowel syndrome / 药学学报

ABSTRACT

This study was designed to explore the interventional mechanism involving "multi-components, multi-targets and multi-pathways" of Gu-Chang-Zhi-Xie pills (GCZX) for treatment of irritable bowel syndrome (IBS) using pharmacological network technology. Firstly, 96 active ingredients from GCZX pills were screened by ADME parameter filtration and chemical space principal component analysis, and the targets of anti-IBS function were predicted using PharmMapper online database. Secondly, AutoDock Vina was used to validate the docking between the active ingredients and predicted disease targets, and to establish the corresponding relationship between "pharmacodynamic molecules and target proteins". Finally, the target elements were mapped into the KEGG biological pathway by CluoGO plug-in, which further elucidates the potential relationship between the key targets and the mechanism of action of Gu-Chang-Zhi-Xie pills for treatment of IBS. The results showed that most of the top 11 key pharmacodynamic molecules were isoquinoline alkaloids, which mainly acted on inflammatory or pain targets, with different degrees of anti-inflammatory and analgesic effects. A total of 39 key targets were identified, including TPH1, TNF-α, IL-6, IFN-γ, MAO-A and IL-10. These targets were mapped to 29 KEGG pathways, of which the P-value of 5-HT signaling pathway was the smallest. Therefore, the pharmacodynamic molecules mainly act on 6 core targets and may play a major role in the regulation of 5-HT signal synthesis or transport pathway. This study sets an example for drug development and mechanistic investigation using innovative technology.