Predicting prospective therapeutic targets of Bombyx batryticatus for managing diabetic kidney disease through network pharmacology analysis.

Abstract

We conducted network pharmacology and molecular docking analyses, and executed in vitro experiments to assess the mechanisms and prospective targets associated with the bioactive components of Bombyx batryticatus in the treatment of diabetic kidney disease (DKD). The bioactive components and potential targets of B batryticatus were sourced from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Using 5 disease databases, we conducted a comprehensive screening of potential disease targets specifically associated with DKD. Common targets shared between the bioactive components and disease targets were identified through the use of the R package, and subsequently, a protein-protein interaction network was established using data from the STRING database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses pertaining to the identified common targets were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Molecular docking simulations involving the bioactive components and their corresponding targets were modeled through AutoDock Vina and Pymol. Finally, to corroborate and validate these findings, experimental assays at the cellular level were conducted. Six bioactive compounds and 142 associated targets were identified for B batryticatus. Among the 796 disease targets associated with DKD, 56 targets were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed the involvement of these shared targets in diverse biological processes and signaling pathways, notably the PI3K-Akt signaling pathway. Molecular docking analyses indicated a favorable binding interaction between quercetin, the principal bioactive compound in B batryticatus, and RAC-alpha serine/threonine-protein kinase. Subsequently, in vitro experiments substantiated the inhibitory effect of quercetin on the phosphorylation level of PI3K and Akt. The present study provides theoretical evidence for a comprehensive exploration of the mechanisms and molecular targets by which B batryticatus imparts protective effects against DKD.