Exploration of Neuroprotective and Retinoprotective Mechanisms of Plumbagin Using Network Pharmacology and Molecular Docking

Research Article

Abstract

Plumbagin, a naturally occurring naphthoquinone, reported to have significant potential in mitigating neuronal and retinal damage. Study of its pharmacokinetic properties reveals favorable drug-likeness and toxicity profiles, supporting its viability as a therapeutic lead. Target prediction and disease-specific gene retrieval identified 50 common targets at the intersection of plumbagin bioactivity and neurodegenerative pathways. Protein-protein interaction networks highlight STAT3, NFKB1, ITGB1, and HDAC2 as primary hub proteins. These targets are intrinsically linked to cellular survival, inflammatory modulation, and oxidative stress management. Functional enrichment indicated that plumbagin primarily operates via the PI3K-Akt, HIF-1, AGE-RAGE, and Toll-like receptor signaling cascades. Molecular docking simulations further validated these findings, showing good binding affinities for plumbagin with STAT3 (-89.86 kcal/mol) and NFKB1 (-88.86 kcal/mol). These interactions indicate a regulatory role in transcriptional activities essential for neuroprotection. The integration of systems-level network pharmacology with site-specific molecular docking characterizes plumbagin as a multi-target phytochemical scaffold capable of stabilizing neuronal integrity. Such evidence provides a computational foundation for developing novel interventions for neurodegenerative and retinopathic conditions.