Study of molecular mechanisms underlying the medicinal plant Tripterygium wilfordii-derived compound celastrol in treating diabetic nephropathy based on network pharmacology and molecular docking

Background: Diabetic nephropathy (DN) is a serious complication of diabetes with rising prevalence worldwide. We aimed to explore the anti-DN mechanisms compound celastrol derived from medicinal plant Tripterygium wilfordii. Methods: Celastrol-related targets were obtained Herbal Ingredients’ Targets (HIT) and GeneCards databases. DN-related retrieved GeneCards, DisGeNET, Therapeutic Database (TTD). A Protein-protein interaction (PPI) network was established using Search Tool for Retrieval Interacting Genes (STRING) database. Gene Ontology (GO) Kyoto Encyclopedia Genomes (KEGG) enrichment analyses performed ClusterProfiler. The cytoHubba plugin used select top 10 hub targets. Molecular docking employing PyMOL AutoDock software. Cell counting kit-8 (CCK-8) flow cytometry assays detect viability apoptosis NRK-52E cells, respectively. mRNA expression levels mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), AKT serine/threonine 1 (AKT1) in cells assessed quantitative real-time polymerase chain reaction (qRT-PCR). Results: sixty-six overlapping DN. GO KEGG demonstrated that core DN mainly involved inflammatory immune response, oxidative stress, advanced glycation end products (AGEs) their receptors (RAGEs) (AGE-RAGE), TNF, interleukin 17 (IL-17), MAPK signaling pathways. Finally, based on good binding activity celastrol, MAPK3, AKT1 identified as foremost celastrol. observed enhanced high glucose (HG)-treated inhibited in vitro assays. Moreover, decreased cells. Conclusion: Celastrol may treat by targeting APK3, regulating responses stress through AGE-RAGE, IL-17,