Abstract

Cnidium monnieri (L.) Cuss, belonging to the Umbelliferae family, is a widely used traditional herbal medicine in ameliorating nephritis. This study was to identify key targets and investigate the molecular mechanism of Cnidium, an extract of Cnidium monnieri that treats diabetic kidney disease, using network pharmacology and bioinformatics. Cnidium's active ingredients and target profiles were extracted from the traditional Chinese medicine systems pharmacology database and analysis platform database. The GEO2R online tool was utilized to mine the differentially expressed genes associated with diabetic kidney disease from the gene expression omnibus database. The diabetic kidney disease-related genes were also obtained from the GeneCards database and compared with the gene expression omnibus databases. Differentially expressed genes and drug targets were mapped to obtain common targets. The Cnidium-active ingredient-target-diabetic kidney disease network was constructed with the help of Cytoscape 3.7. As a result, we found that Cnidium has 19 compounds and 98 targets, among which beta-sitosterol and ostruthin played major roles in treating diabetic kidney disease. The key targets comprised prostaglandin-endoperoxide synthase 2, caspase-3, estrogen receptor 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), mammalian target of rapamycin, matrix metallopeptidase 9. The protein-protein interaction network of common targets was constructed using the search tool for the retrieval of interacting genes/proteins database. The David database was used for gene ontology and kyoto encyclopedia of genes and genomes pathway enrichment analysis for key targets. Gene ontology analysis revealed that these key targets regulated apoptosis and protein serine/threonine/tyrosine kinase activity. The kyoto encyclopedia of genes and genomes analysis indicated that the calcium signaling pathway, interleukin-17 signaling pathway, cyclic adenosine 3′,5′-monophosphate signaling pathway, and advanced glycation end products receptor for advanced glycation end products signaling pathway were involved in diabetic complications treatment. The key targets were verified by molecular docking with active ingredients. The results showed that beta-sitosterol and ostruthin bind to caspase-3 and estrogen receptor 1. From the perspective of network pharmacology, we found that the possible mechanism of Cnidium in treating diabetic kidney disease involves the interaction between beta-sitosterol and caspase-3, ostruthin and estrogen receptor 1.