Exploring the mechanism of Bushen KaiXuan Tongluo formula in ameliorating diabetic kidney disease based on transcriptomics and animal experiments

BACKGROUND: Diabetic kidney disease (DKD) is a major microvascular complication of diabetes Mellitus (DM), characterized by insulin resistance and renal cell apoptosis. Bushen Kai Xuan Tongluo Formula (BKT), a traditional Chinese medicine compound based on the theory of "kidney deficiency, blood stasis, and obstruction of Xuan Fu," shows nephroprotective potential, but its molecular mechanisms remain unclear. This study employed transcriptomic profiling to investigate BKT's renoprotective effects, focusing on the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in regulating glucolipid metabolism and apoptosis. METHODS: Transcriptomic analysis was performed on renal tissues from db/db mice to identify key pathways post-BKT intervention. Mice were divided into normal control, model, BKT low-/medium-/high-dose, and irbesartan groups. Renal function, glycolipid metabolism, and histopathology were assessed. Protein expression of PI3K/AKT pathway components (p-PI3K, PI3K, p-AKT, AKT, p-CREB, CREB, FOXO1, GSK-3β) and apoptosis markers (BCL-2, BAX, Caspase-3) was evaluated by Western blot and immunohistochemistry (IHC). mRNA levels of PI3K, AKT, CREB, BCL-2, and BAX were measured by reverse transcription quantitative real-time PCR (RT-qPCR). RESULTS: BKT significantly improved glycolipid metabolism, renal function, and histopathological lesions in db/db mice. Transcriptomic analysis identified the PI3K/AKT pathway as the most enriched. BKT upregulated mRNA expression of PI3K, AKT, and CREB, and downregulated BAX. Mechanistically, BKT activated the PI3K/AKT/CREB cascade, modulated FOXO1 and GSK-3β, and suppressed apoptosis by increasing BCL-2 and decreasing BAX and Caspase-3 expression. CONCLUSION: BKT protects against DKD by activating the PI3K/AKT pathway, regulating downstream factors (CREB, FOXO1, GSK-3β), and inhibiting renal cell apoptosis. This study provides molecular evidence supporting BKT's potential clinical application.