A Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of Shuilu Erxian Dan in Treating Diabetic Kidney Disease

Background and objective: Recent years, some Chinese scholars have applied Shuilu Erxian Dan (SED) to the treatment of treating diabetic kidney disease (DKD) and achieved well curative effect. However, these studies are mostly limited to clinical observation. This study aimed to explore the molecular mechanisms of SED in treating DKD. Methods The active components of SED were retrieved in TCMSP database and BATMAN-TCM database, and the herbal targets were obtained by drugbank database and SwissTargetPrediction platform. The gene expression data of DKD patients were downloaded from GEO database and analyzed to obtain DKD-related targets. The ingredient-target network and the PPI network were constructed by Cytoscape software. The clusterProfiler package of R software is used for bioinformatic analysis. Molecular docking was further applied to verify the interaction between compounds and targets by Autodock Vina software. Results 610 differential expressed genes of DKD patients were obtained, and 29 potential targets of SED against DKD were screened out (including PPTGS2, FABP3, HSD17B2, FABP1, HSD11B2, CYP27B1, JUN, UGT2B7, VCAM1, CA2, MAOA, MMP2, CXCR1, SLC22A6, EPHX2, SLC47A1, FOS, EGF, CCL2, COL3A1, GSTA1, GSTA2, HSPA1A, DAO, ALDH2, ALB, GPR18, FPR2, and LPL). All the active ingredients in SED can act on the DKD-related targets, among which quercetin, Ellagic acid, and kaempferol may be the key active compounds. SED may play a therapeutic role in DKD by regulating pathways including “Fluid shear stress and atherosclerosis”, “AGE − RAGE signaling pathway in diabetic complications” and “IL-17 signaling pathway”. Conclusion This study suggests that the mechanism of SED treating DKD is a complex network with multi-target and multi-pathway, which provides a reference for future experimental studies.