Haizao Yuhu Decoction Inhibits Goiter via p53 Pathway-Induced Apoptosis: Metabolomic and Cellular Assay Analysis

Haizao Yuhu Decoction (HYD), a classic Traditional Chinese Medicine (TCM) formula, is used to treat Yingbing, which corresponds to goiter in modern medicine. Although HYD has been extensively studied for goiter, its specific active components and the underlying mechanisms of action remain to be fully elucidated. This study investigated the effects and mechanisms of HYD in goiter using untargeted LC-MS metabolomics (comparing HYD decoction and HYD-containing serum), network pharmacology for target prediction, and in vitro validation with a TSHR human monoclonal antibody M22 (TSHR hMAb M22)-induced thyroid cell proliferation model, followed by Western blotting to verify key pathway proteins. The comparison of metabolomic profiles between HYD decoction and HYD-containing serum revealed that 2091 metabolites (90.05%) were downregulated, while 231 were upregulated in medicated serum. Network pharmacology predicted targets including AKT1, PIK3CA, ESR2, ESR1, and TP53. HYD-containing serum exhibited pro-apoptotic effects on the cell proliferation model. The underlying mechanism may primarily involve the upregulation of the p53/PUMA/p21 pathway, which subsequently affects caspase-3 activity. Furthermore, the action of HYD may involve non-p53 multiple signaling pathways. HYD may exert its effects by modulating multiple signaling pathways, including p53/PUMA/p21, leading to apoptosis in thyroid cells.