The Mechanism of Plantaginis Semen in the Treatment of Diabetic Nephropathy based on Network Pharmacology and Molecular Docking Technology

Background: Diabetic nephropathy (DN) is one of the common complications of diabetes. Plantaginis Semen (PS) has a variety of therapeutic effects, however its mechanism on DN is unclear. Objective: This paper aims to find the ingredients, the key targets, and the action pathways of PS on DN from the perspective of network pharmacology. Methods: The databases of network pharmacology, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Pharmmapper, OMIM, DrugBank, Gene-Cards, TTD, Disgenet, STRING, and Cytoscape software, were used to find the main ingredients and targets. Gene Ontology (GO) function and Kyoto Encyclopedia of Genome and Genomes (KEGG) pathway enrichment analysis were used to reveal the potential pathways of the PS on DN. The GEO database was used to find the targets of DN based on valid experimental research. The molecular docking technology was used to evaluate the combination between ingredients of PS and the targets. Results: A total of 9 active ingredients and 216 potential therapeutic targets were obtained for PS on DN. Hub targets were discovered by the Cytoscape software analysis. CASP3 was screened by Venn diagram by making intersection between GSE30529 and hub genes. Moreover, CASP3 was combined with one of the nine active ingredients, quercetin, by molecular docking analysis. The KEGG pathways were mainly involved in diabetic nephropathy, and were simultaneously associated with CASP3 as followed: AGE-RAGE signaling pathway in diabetic complications, apoptosis, lipid and athero-sclerosis, MAPK signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and p53 signaling pathway. Conclusion: PS can have the treatment on DN through CASP3. Quercetin, as one of the nine active ingredients, can be bounded to CASP3 to inhibit apoptosis in DN. PS can also take action on DN probably through many pathways. The role of PS on DN through other pathways still needs to be further elaborated.