Elucidating the Therapeutic Mechanism of Danggui Liuhuang Decoction in Hyperthyroid Kidney Disease: An Integration of Network Pharmacology and Metabolomics

<b>Background and Objective:</b> Danggui Liuhuang decoction (DLD) demonstrates pharmacological efficacy in the treatment of hyperthyroid kidney disease (HKD). However, the underlying therapeutic mechanism remains inadequately understood. This study aims to elucidate the therapeutic mechanism of DLD in HKD rats by integrating the determination of effective component content, network pharmacology, in vivo verification, and metabolomics, with a focus on the alterations in metabolites and metabolic pathways. <b>Methods:</b> The concentrations of 12 components, including berberine, in DLD were quantified using high-performance liquid chromatography. Network pharmacology was utilized to investigate the interactions between drug targets and disease targets and to predict functional pathways. A rat model of HKD was established to verify the therapeutic mechanism of DLD, which was further elucidated through metabolomics analysis. <b>Results:</b> The quantification of 12 components, including berberine, in DLD was successfully achieved. Key targets such as TNF and AKT1, along with the PI3K/AKT and MAPK signaling pathways, were identified as critical pathways through network pharmacology analysis. Animal experiments robustly demonstrated the therapeutic efficacy of DLD on HKD, corroborating the network pharmacology findings via histopathological analysis, ELISA, and Western blot (WB). Metabolomics studies revealed significant alterations in 49 metabolites pre- and posttreatment, with notable changes in linoleic acid metabolism and arachidonic acid metabolism pathways. Linoleic acid, arachidonic acid, and 5-HETE were identified as potential biomarkers. <b>Conclusion:</b> The therapeutic efficacy of DLD in HKD rats was substantiated, and the underlying mechanisms were preliminarily elucidated, thereby providing a foundation for further investigation into the pharmacodynamic substances and mechanisms of action.