Discovery of the pharmacodynamic material basis of Danggui Buxue Decoction in the treatment of diabetic kidney disease based on lipidomics regulation

BACKGROUND: Danggui Buxue Decoction (DBD) is a formula used for treating diabetic kidney disease (DKD). However, the pharmacodynamic material basis of DBD in DKD therapy remains unclear, hindering its industrial development and innovation in drug formulations. PURPOSE: Lipid metabolism disorder is a key pathological mechanism in DKD progression. This study employs lipidomics to elucidate and validate the pharmacodynamic material basis of DBD in treating DKD. METHODS: Forty-eight male SD rats were used in the experiment, with 8 rats per group. The DKD model was constructed with a diet high in fat and sugar, together with intraperitoneal administration of low-dose STZ and unilateral nephrectomy. DBD was administered continuously for 10 weeks to assess its therapeutic efficacy on DKD. Lipid biomarkers in the DKD models were analyzed using lipidomics, while the transitional components in the blood of DBD-treated rats were characterized through UPLC-QE-Orbitrap MS. Potential pharmacodynamic substances were identified by correlating lipid biomarkers with active ingredients in vivo, followed by molecular docking and in vitro experiments to validate key pharmacodynamic components. RESULTS: DBD significantly improved blood glucose, blood lipid levels, and renal function in DKD model rats. Lipidomics identified 37 lipid biomarkers in the DKD models, and DBD demonstrated a marked corrective effect on these biomarkers. In the therapeutically effective state, 91 blood transitional components of DBD were identified. Correlation analysis revealed 44 pharmacodynamic substances associated with DKD treatment, with ferulic acid, calycosin, astragaloside IV, and ligustilide being the key components. These substances acted by increasing the levels of SIRT1, PPARG, and ABCA1 proteins in lipid-deposited podocytes. CONCLUSION: In conclusion, this study explained the scientific connotation of DBD treatment of DKD with modern scientific language from three aspects: pharmacodynamic evaluation, pharmacodynamic material basis and mechanism of action from the perspective of lipid metabolism balance for the first time, and provided an empirical basis for the modern application of traditional Chinese medicinal prescriptions.