Exploring the Protective Effect and Mechanism of Buddlejae Flos on Sodium Selenite-Induced Cataract in Rats by Network Pharmacology, Molecular Docking, and Experimental Validation

Objective. Buddlejae Flos has a long history of utilization by humans to treat ophthalmic diseases. Although in vitro study revealed that it can be used for treating cataract, the bioactive components and the mechanism of efficacy remained unclear. This study aims to discover the bioactive components and mode of efficacy of Buddlejae Flos in cataract treatment. Methods. Several databases were screened for bioactive components and corresponding targets, as well as cataract-related targets. Using the String database, common targets were determined and utilized to construct protein-protein interactions (PPI). The drug-component-target-disease network map was drawn using Cytoscape software. R language was utilized to execute Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analysis. Molecular docking was done through Schrodinger Maestro software utilization. Luteolin's (LUT) effect on cataract induced by sodium selenite in rat pups was evaluated. Results. Six bioactive components with 38 common targets were identified as being associated with cataract. TP53, AKT1, EGFR, CASP3, TNF, ESR1, INS, IL6, HIF1A, and VEGFA were identified as core targets in PPI analysis, and the binding energy of LUT with AKT was the lowest. LUT has been demonstrated to significantly lower MDA levels, raise glutathione (GSH) levels, and boost the activity of antioxidant enzymes like GST, SOD, GPx, and CAT. After LUT treatment, TNF-a, IL-2, and IL-6 levels were significantly lowered. Bcl-2 mRNA expression levels and p-PI3K and p-AKT protein expression were significantly elevated. In contrast, caspase-3 and Bax mRNA expression levels were significantly decreased. Conclusion. This study demonstrates that LUT is a possible bioactive component that may be utilized for cataract treatment. Its mode of action includes oxidative stress suppression, reducing inflammation, and inhibiting apoptosis via regulating the PI3K/AKT single pathway.