Mechanism of action of Buqing Granule against Diabetic retinopathy based on network pharmacology and animal experiments

Abstract

ObjectiveFor this study, network pharmacology and animal experiments were used together to get a better idea of how BQKL works at the molecular level to treat DR. MethodsIn this study, we obtained the relevant action target information of BQKL from the TCMSP and also combined the GeneCards, OMIM, TTD, and PharmGKB databases with the GEO database to obtain the relevant target information of DR. The intersection of these targets was determined using a Venn diagram to identify the target of action for the treatment of DR with BQKL. The target proteins of BQKL for DR were then uploaded to the String database. The resultant data were imported into Cytoscape 3.9.0 to construct PPI networks and identify key targets of action. The DAVID database was used to do a GO and KEGG pathway enrichment analysis of target genes for treating DR with BQKL. Molecular docking was performed to validate the core action targets with the core compounds of BQKL. In addition, we induced DR production in rats by a high-fat, high-sugar diet and intraperitoneal injection of STZ and validated the results obtained from the network pharmacological analysis by changes in body weight and blood glucose, serum levels of biochemical markers, HE staining, immunohistochemistry, qRT-PCR, and Western blot experiments in rats. ResultsIn this study, quercetin, kaempferol, {beta}-sitosterol, lignanserin, and stigmasterol were identified as the key components, TP53, AKT1, JUN, CASPASE3, MAPK3, and MAPK1 as the key targets, and PI3K-Akt, AGE-RAGE, and MAPK signaling pathways as the main pathways involved. The results of animal experiments showed that BQKL could not only effectively reduce the degree of blood glucose, blood lipids, and oxidative damage in diabetic rats but also slow down the development process of DR. At the same time, it can significantly up-regulate the expression of AKT1, MAPK1, and MAPK3 and down-regulate the expression of CASPASE3, c-JUN, and TP53 in retinal tissue. ConclusionBQKL ameliorates oxidative stress, apoptosis, and inflammation due to hyperglycemia-related stress by regulating key targets of CASPASE3, AKT1, c-JUN, TP53, MAPK1, and MAPK3, thereby delaying the onset and progression of DR.