Background: Diabetic kidney disease (DKD), a common complication of diabetes, increasingly threatens patients. Approximately 20%-40% of diabetic patients develop DKD, with 30%-50% progressing to end-stage renal disease. QingReYiQiHuoXue Formula (QRF) has demonstrated clinical efficacy in treating DKD, yet its underlying mechanisms remain unclear. Purpose: This study aimed to explore the mechanisms of QRF in treating DKD and to validate its effects on lipid abnormalities and ferroptosis in a DKD mouse model.
Methods: An integrated approach, encompassing network pharmacology, molecular biology, pharmacodynamics, and lipidomics, was employed to elucidate the mechanisms of QRF in treating DKD. Network pharmacology was initially used to predict potential pathways and targets of QRF in treating DKD, along with potential targets for ferroptosis from the ferroptosis database. The efficacy was then validated in a DKD mouse model induced by HFD and STZ injection, including blood and urine tests, histopathological analysis, ferroptosis level measurement, and lipidomic analysis.
Results: Through network pharmacology, we discovered that QRF may regulate both the PI3K/AKT/GSK3β signaling pathway and ferroptosis. In vivo experiments confirmed QRF's renal protective effects in HFD/STZ-induced DKD mice, significantly reducing blood glucose levels, ameliorating blood lipid abnormalities, and reducing renal tissue damage. Lipidomic analysis revealed QRF's regulatory effects on renal lipid metabolism, particularly in reducing levels of polyunsaturated fatty acids (PUFAs) associated with ferroptosis. Further validation showed QRF's potential in modulating ferroptosis and the PI3K/AKT/GSK3β signaling pathway.
Conclusion: QRF alleviates renal damage in a diabetic mouse model by modulating the PI3K/AKT/GSK3β signaling pathway, improving lipid metabolism disorders, and suppressing ferroptosis. This study offers preliminary insights into the mechanisms of QRF in treating DKD.
Y. Wei: None. L. Zhang: None.
