The study aimed to identify the key active components in Silybum marianum (S. marianum) and determine how they protect against nonalcoholic fatty liver disease (NAFLD).

The KEGG pathway and GO biological process enrichment, biological annotation, as well as the identified hepatoprotective core gene targets were analyzed using the Metascape database.

The effect of silymarin on NAFLD was determined using H&E on pathological alterations in liver tissues.

Liver function level was evaluated using biochemical tests. Western blot experiments were used to observe the proteins that were expressed in the associated signaling pathways on the hepatoprotective effect, which the previous network pharmacology predicted.

The present study provided new sights and a possible explanation for the molecular mechanisms of S. marianum against NAFLD.