To explore the potential mechanism of the rhubarb-Salvia miltiorrhiza herb pair in the intervention of diabetic kidney disease (DKD) by integrating Gene Expression Omnibus (GEO) data mining, network pharmacology, and molecular docking techniques.

Active ingredients and potential targets of rhubarb-Salvia miltiorrhiza were obtained through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database combining with the Chinese Pharmacopoeia and relevant literature. The glomerular dataset GSE30528 and the tubular dataset GSE30529 related to DKD were retrieved from the GEO database, and differential analysis was performed in the two types of tissues to screen exploratory candidate targets. Protein-protein interaction analysis was performed using the STRING database, and the target network was constructed with Cytoscape software, while GO functional annotation and KEGG pathway enrichment analysis of key targets were conducted via R language. Finally, molecular docking verification was carried out using AutoDock Vina.

From rhubarb-Salvia miltiorrhiza, a total of 90 active ingredients, 150 potential targets, and 3, 592 candidate differential targets for DKD were screened out, yielding a total of 43 intersecting targets. Topological analysis identified the core targets as EGFR, CASP3, ICAM1, KDR, and MAPK1, and the core components as emodin, aloe-emodin, danshensu, and tanshinone ⅡA. Go enrichment involved epithelial cell proliferation and apoptosis, ERK1/2 cascade reaction, and collagen-containing extracellular matrix. KEGG enrichment was mainly observed in PI3K/Akt, MAPK, integrin, and HIF-1 signaling pathway. Molecular docking showed that the binding energies of emodin and tanshinone ⅡA to the core target EGFR were -9.32 and -9.59 kcal/mol, respectively, both exhibiting favorable theoretical binding activity.

The rhubarb-Salvia miltiorrhiza herb pair may participate in the pathological processes associated with DKD through a multi-component, multi-target, and multi-pathway network. The signal networks related to emodin, tanshinone ⅡA, and EGFR can serve as candidate directions for subsequent in-vivo and in-vitro verification.