Integrating network pharmacology, transcriptomics, and molecular simulation to reveal the mechanism of tert-butylhydroquinone for treating diabetic retinopathy

Diabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, is a significant cause of blindness. As one of the crucial factors in the pathogenesis of DR, oxidative stress provides new insights for the treatment of DR. Tert-butylhydroquinone (TBHQ), an efficient phenolic antioxidant, has been proved to inhibit diabetic retina injury. However, the mechanism of TBHQ for DR treatment is still unclear. The present study was designed to investigate the potential mechanism of TBHQ for treating DR. Firstly, the potential targets of TBHQ and DR were selected to construct protein-protein interaction network, which was applied to illustrate the potential mechanism of TBHQ against DR. Combined with transcriptomics and molecular simulation, the potential mechanisms were systematically verified. The results showed that TBHQ inhibited retinal microvascular injury by regulating oxidative stress, inflammation, cell proliferation-death regulation, and vascular system development. The mechanisms of these activities were associated with hypoxia-inducible factor-1 (HIF-1), nuclear factor-erythroid 2 related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), forkhead box O (FoxO), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), and rhoptry-associated protein1 (Rap1) signaling pathways and their related targets nitric oxide synthase 3 (NOS3), mitogen-activated protein kinase 8 (MAPK8), prostaglandin-endoperoxide synthase 2 (PTGS2), and heme oxygenase 1 (HMOX1). In conclusion, a systematic perspective for the mechanism of TBHQ against DR was revealed by present study which lays a foundation for the application of TBHQ in treating DR.