Integrative network pharmacology and molecular modeling approaches reveal the therapeutic potential of Syzygium samarangense phytocompounds against diabetes retinopathy

Abstract

Introduction Diabetes retinopathy (DR) is a progressive microvascular complication of diabetes mellitus characterized by oxidative stress, inflammation, and neurovascular dysfunction. Current therapies provide limited efficacy, highlighting the need for multi-targeted, natural therapeutic alternatives. Syzygium samarangense (SS) is a phytochemical-rich medicinal plant with potential anti-Diabetes properties. Methodology A data-driven systems pharmacology approach was employed to explore the anti-DR potential of S. samarangense phytochemicals. Twenty-nine active compounds were screened for drug-likeness using Lipinski’s Rule of Five. Overlapping targets between SS and DR were identified, yielding 403 shared targets. Network pharmacology analysis highlighted ten core proteins, including SRC, ALB, GAPDH, and TNF. Gene Ontology (GO) and KEGG pathway enrichment analyses identified key pathways such as AGE-RAGE and HIF-1 signaling. Molecular docking was performed to evaluate ligand–target interactions, followed by 500 ns molecular dynamics (MD) simulations and MM-GBSA binding free energy analysis for validation. Results and Discussion Docking studies identified Pinocembrin (SS5) and Stercurensin (SS4) as top-ranked ligands, with strong binding affinities toward SRC and ALB, respectively. MD simulations demonstrated superior structural stability for the SS5–SRC complex, whereas SS4–ALB exhibited moderate stability. MM-GBSA calculations further confirmed favorable binding energies, supporting their drug-like behavior. These multi-target interactions suggest that S. samarangense phytochemicals can modulate key DR-associated pathways. Conclusion S. samarangense exhibits promising multi-target activity against Diabetes retinopathy. Pinocembrin (SS5) and Stercurensin (SS4) emerge as potential lead compounds for further experimental validation and drug development.