Integrated metabolomics, network pharmacology, and molecular docking to reveal the mechanisms of Isodon excisoides against drug‐induced liver injury

Abstract Isodon excisoides (Y.Z.Sun ex C.H.Hu ) H. Hara has been often used to treat liver diseases in folk medicine. However, the potential hepatoprotective mechanism of I. excisoides remains unclear. In this study, the mechanism of I. excisoides in alleviating drug‐induced liver injury (DILI) was explored using a strategy combining metabolomics with network pharmacology for the first time. First, serum metabolomics was applied to identify differential metabolites and enrich metabolic pathways. The potential targets of I. excisoides for the treatment of DILI were investigated by network pharmacology. Subsequently, a comprehensive network of network pharmacology and metabolomics was established to find the key genes. Finally, molecular docking technology was used to further verify the key targets. As a result, four key genes including TYMS , IMPDH2 , DHODH , and ASAH1 were identified. The proteins produced by these genes had high affinity with the corresponding diterpenoids. These results indicate that the components of I. excisoides play a liver‐protective role by affecting the aforesaid key genes and key proteins. Our results offer a novel strategy for determining the pharmacological effects and potential targets of natural compounds.