Based on Network Pharmacology and Molecular Docking: Exploring the Mechanism of Salvia Miltiorrhiza - Tripterygium Wilfordii Combination Therapy for Diabetic Nephropathy

Abstract

Objective: To explore the mechanism of Salvia miltiorrhiza-Tripterygium wilfordii Hook. f. in the treatment of diabetic nephropathy based on network pharmacology and molecular docking. Methods: Effective components of the drug pair Salvia miltiorrhiza and Tripterygium wilfordii were screened from the TCMSP database. Relevant targets of the drug pair components were obtained from SwissTargetPrediction. Diabetic nephropathy (DN) targets were acquired through GeneCards, OMIM, and DisGeNET databases. The relevant targets of the drug pair components and the disease targets were uploaded to an online Venn diagram to obtain their intersection targets. The intersection targets were uploaded to the STRING database to construct a protein-protein interaction (PPI) network diagram. Cytoscape 3.9.1 software was used to filter core targets and construct a "drug pair-effective components-intersection targets" network diagram. GO and KEGG enrichment analysis were performed in the Metascape database, and the results were visualized using the online graphing website, "VennDiagram". The core targets predicted by network pharmacology and components were validated using molecular docking technology. Results: A total of 56 effective components of Salvia miltiorrhiza and 34 effective components of Tripterygium wilfordii were collected from the databases. There were 682 related targets for Salvia miltiorrhiza components and 654 for Tripterygium wilfordii components. A total of 1653 DN targets were obtained from the disease database. After the intersection of disease targets and drug pair component targets, 129 potential action targets were obtained. The key targets for the treatment of DN through PPI network were identified as TNF, AKT1, PPARG, and SRC, with key components such as luteolin and kaempferol. GO and KEGG enrichment analysis showed that the treatment of DN with Salvia miltiorrhiza-Tripterygium wilfordii mainly involves pathways related to cancer, lipid and atherosclerosis, IL-17 signaling pathway, and diabetic complications AGE/RAGE, among others. Molecular docking results showed that active components have good binding ability with core targets. Conclusion: Salvia miltiorrhiza-Tripterygium wilfordii mainly exerts its therapeutic effect on DN through active components such as luteolin and kaempferol, targeting related targets such as TNF, AKT1, PPARG, and SRC, and participating in multiple signaling pathways such as cancer-related pathways, lipid and atherosclerosis, IL-17 signaling pathway, and diabetic complication AGE/RAGE.