Erzhi pill for diabetic nephropathy: validation of integrated network pharmacology, molecular docking, proteomics, and transcriptomics

OBJECTIVE: The study aimed to investigate the mechanism of Erzhi Pill in treating diabetic nephropathy (DN) using network pharmacology and molecular docking, with animal experiments providing additional validation. METHODS: Initially, the molecular basis and potential mechanisms of Erzhi Pill were examined through network pharmacology, followed by molecular docking between its core components and key potential targets to corroborate the network pharmacology findings. These results were then validated through experimental approaches. RESULTS: Network pharmacology analysis and HPLC fingerprinting identified Specnuezhenide and wedelolactone as primary components, demonstrating effective binding between the core components and key targets, thus confirming the predictions. In vivo experiments revealed that Erzhi Pill markedly improved blood glucose, lipid profiles, insulin resistance, and kidney function in db/db mice, while also reversing renal cell pathological changes. Transcriptomics and proteomics analyses of KEGG-enriched differential proteins suggested that the preventive and therapeutic effects of Erzhi Pill on DN may operate through AGE-RAGE, PPAR, and other related signaling pathways. CONCLUSION: Overall, the combined findings from network pharmacology, molecular docking, and experimental validation elucidate the mechanism by which Erzhi Pill inhibits renal fibrosis in DN.