Deciphering the Role of Honey in Ocular Diseases by Integrating Network Pharmacology and Molecular Modeling Approaches for Retinal Therapy

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of vision impairment globally. Limitations of conventional therapies highlight the need for alternative treatments. Honey-derived bioactive compounds are known for their antioxidant,antiinflammatory, and antidiabetic properties. This study employs a systems pharmacology approach combined with molecular modeling to explore the efficacy of honey bioactives in targeting key molecular pathways associated with DR and AMD. A total of 170 honey-based bioactives were retrieved through literature mining. Absorption, distribution, metabolism, excretion and toxicity (ADMET) profiling identified five promising compounds, taxifolin, morin, epicatechin, rhamnetin and quercetin, based on drug-likeness and oral bioavailability. Gene expression datasets from gene expression omnibus (GEO) revealed 588 common disease-associated genes, which were subjected to functional enrichment (DAVID) and network construction (Cytoscape). Key signaling pathways, including HIF-1 and inflammatory responses, were enriched. Hub genes such as STAT3, EGFR, HSP90AA1, SRC, AKT1, TNF, HIF1A, EP300, BCL2 and MAPK1 were identified via protein–protein interaction (PPI) analysis. Molecular docking evaluated the binding potential of selected compounds with EP300, HIF1A and BCL2. Structural stability was assessed using density functional theory (DFT), and dynamic behavior was validated through molecular dynamics (MD) simulations. Results: The selected honey constituents exhibited strong binding affinities with key retinal disease proteins and modulated multiple pathological pathways, including oxidative stress, angiogenesis and inflammation. DFT analysis confirmed structural stability, while MD simulations validated the robustness of protein–ligand interactions. Conclusion: Taxifolin, morin, epicatechin, rhamnetin and quercetin demonstrate promising therapeutic properties for the treatment of DR and AMD. These findings support the potential of honey bioactives as multi-target agents; however, further in vitro and in vivo studies are warranted to confirm their clinical applicability.