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

Isodon excisoides (Y.Z.Sun ex C.H.Hu) H. Hara has been often used to treat liver diseases in folk. But the potential hepatoprotective mechanism of Isodon excisoides was unclear. In this paper, the mechanism of Isodon excisoides in alleviating drug induced liver injury (DILI) was explored by a strategy of combining metabolomics with network pharmacology for the first time. Firstly, serum metabolomics was applied to identify differential metabolites and enrich metabolic pathways. The potential targets of Isodon 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, 4 key genes including TYMS, IMPDH2, DHODH and ASAH1 were found. The proteins produced by these genes had high affinity with the corresponding diterpenoids. It indicated that the components of Isodon excisoides play a liver protective role by affecting these key genes and key proteins. These results offered a novel strategy for determining the pharmacological effects and potential targets of natural compounds.