Abstract
Background: Diabetic retinopathy (DR) is a microvascular complication of diabetes characterized by damage to the retina's neurons and blood vessels. Ginkgo biloba extract (GBE) has demonstrated neuroprotective properties, however, its specific mechanisms in DR remain incompletely understood. This research aims to elucidate the underlying mechanisms of GBE in DR. Methods and results: A diabetic rat model was induced with streptozotocin (STZ) and divided into control, diabetic, and GBE-treated groups. Retinal tissues of each group were analyzed using histology, TUNEL staining, and immunofluorescence. Bioinformatics identified potential GBE targets for DR, and protein-protein interaction network analysis prioritized core targets. Western blot and immunoprecipitation assays were used to detect protein expression and ubiquitination status. We successfully constructed the DR rat models and observed that GBE intervention effectively reverses diabetes-induced hyperglycemia and mitigates retinal ganglion cell (RGC) damage in the DR rat model. TUNEL staining indicates GBE's protective role against RGC apoptosis induced by DR. Bioinformatics identified 135 GBE targets in DR, with a focus on apoptosis pathways. Critically, we demonstrated an upregulation of TP53 expression in the retinal tissues of the DR rat model, an effect that was successfully reversed following GBE intervention. Notably, GEB increased TP53 ubiquitination, suggesting a potential modulation of TP53 stability and function. Conclusions: GBE attenuates DR progression by modulating TP53 ubiquitination in a rat model. The findings highlight the potential therapeutic benefits of GBE in DR and suggest further investigation into its mechanisms and broader bioactivity pathways.