Glycosylation Matters: Network Pharmacology-Based and Molecular Docking Analysis of Resveratrol Glycosylated Derivatives on Parkinson's Disease.

Resveratrol (RV), a natural polyphenol, has been extensively studied for its neuroprotective potential in Parkinson's Disease (PD), but its clinical translation is limited by poor bioavailability and rapid metabolism. Glycosylated derivatives, including polydatin and resveratrol-3-α-glucoside, have been proposed to improve the solubility and stability. This study compared the pharmacokinetic properties of RV and its derivatives and examined their molecular interactions with PD-related targets. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis showed that, despite improved solubility, RV retained a more favorable overall pharmacokinetic profile. Target prediction combined with Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network construction identified 50 potential targets, with 11 prioritized for molecular docking. Glycosylated derivatives exhibited binding affinities for all targets stronger than those of RV, with TNF-α, PPARγ, and ERBB2 highlighted as key candidates. These findings indicate that RV glycosylation may enhance therapeutic potential for PD treatment by promoting stronger molecular interactions with critical targets, though in vivo validation remains necessary.