Exploring the mechanisms underlying the therapeutic effect of the drug pair Rhubarb-Coptis in diabetic nephropathy using network pharmacology and molecular docking analysis.

Abstract

To use network pharmacology to explore the mechanism of the drug pair Rhubarb-Coptis in the treatment of diabetic nephropathy (DN). The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of drug pair Rhubarb-Coptis. Targets were obtained using the TCMSP and SwissTargetPrediction databases. DN disease targets were extracted from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and Therapeutic Target database (TTD) databases. A "drug-compound-target" network and protein-protein interaction (PPI) network were constructed and analyzed through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape software. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed using AutoDock Vina and PyMOL software. A total of 30 active components and 609 targets of Rhubarb-Coptis were screened out, and 98 common targets of DN and Rhubarb-Coptis were obtained. Quercetin, berberine, epiruberine, epautin, and moupinamide were the main active components in the treatment of DN. The STAT3, CTNNB1, PIK3R1, PIK3CA, and TP53 genes were identified as the potential 5 key targets. The GO enrichment analysis showed that these 5 key targets mainly involved in inflammation, oxidative stress, and apoptosis. KEGG enrichment analysis showed that the pathways were mainly enriched in the AGE-RAGE and HIF-1 signaling pathways. Molecular docking revealed that the 5 key targets could combine well with their corresponding active compounds. This study expounds the therapeutic effect of Rhubarb-Coptis on DN from a holistic perspective, and provides a valuable basis for clinical application and academic research.