This study, taking the foundational efficacy of AS against DKD and its active compounds as the starting point, combined bioinformatics analysis with experimental validation, elucidates the mechanism by which AS regulates podocyte apoptosis and ECM metabolism in DKD mice via the mitogen-activated protein kinase/FOS (MAPK/FOS) signaling pathway. Here, WNK2 is linked to diabetic kidney disease.