Compound Analysis and Mechanistic Exploration of Shen-Yan-Fang-Shuai Formula in Diabetic Kidney Disease: An...

Diabetic kidney disease (DKD) is significantly impacting both quality of life and survival rates. The Shen-Yan-Fang-Shuai (SYFS) formula is a traditional Chinese medicine (TCM) compound widely used in the clinical treatment of DKD with proven efficacy, though its potential mechanism of action remains unclear. This study attempts to elucidate the therapeutic efficacy, mechanisms of action, and active compounds of the SYFS formula in the treatment of DKD.

The components of SYFS formula were identified by UHPLC-MS/MS. Differentially expressed genes (DEGs) and key module genes were selected based on the GEO database to obtain intersection targets. Protein-protein interaction (PPI) network and component-target network were constructed. Machine learning (ML) was employed to screen for hub genes, which were validated through nomogram, immune infiltration analysis, molecular docking and molecular dynamics (MD) simulation. Subsequently, our findings were validated through a combination of transcriptomic sequencing of renal tissue from animal models and real-time quantitative PCR (qPCR) analyses performed on both the animal tissues and HK-2 cells.

154 chemical components and 994 targets were identified in the SYFS formula. Intersection with DEGs and WGCNA module genes identified 39 potential targets. Five hub genes (MMP3, MMP12, PTGES, SST, and DUSP1) were selected through ML and used to construct a nomogram. Multiple immune cell infiltration levels were significantly elevated in DKD, with hub genes showing correlations with specific immune cell types. Molecular docking and MD simulation validated the binding capacity between components of the SYFS formula and key targets. In addition, it has been further verified in animal experiments and cell experiments.

The core components of the SYFS formula, including naringenin chalcone, palmatine, oleanonic acid, β-elemonic acid, and Naringenin, likely exert their effects through the MMP3, MMP12, PTGES, SST, and DUSP1 targets. This research offers empirical support for the application of the SYFS formula in DKD, establishing a crucial groundwork for subsequent clinical investigations.