Background
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss driven by oxidative stress, neuroinflammation, and protein misfolding. Natural products like ginger (Zingiber officinale) contain neuroprotective sesquiterpenes that may modulate these processes. This study aimed to evaluate the neuroprotective potential of ginger extract and its key bioactive compounds, α-santalol and β-eudesmol, using integrated computational approaches.
Methods
Ginger extract was profiled using GC-MS and LC-MS to identify major constituents. Network pharmacology tools (STRING, Metascape) were used to identify PD-related targets and construct protein-protein interaction networks. Pharmacokinetic and ADMET properties of α-santalol and β-eudesmol were predicted using SwissADME and pkCSM. Molecular docking was performed against PD-associated targets, including LRRK2, to explore potential binding interactions.
Results
Chemical profiling identified major bioactive compounds, including sesquiterpenes like α-santalol and β-eudesmol, with significant neuroprotective properties. Pharmacokinetic analysis revealed favorable BBB permeability, intestinal absorption, and low toxicity. Molecular docking demonstrated strong interactions with PD-related targets, particularly LRRK2, with binding energy values indicating effective target engagement. Pathway enrichment analysis highlighted the involvement of key pathways including NF-κB and Nrf2/ARE in mitigating oxidative stress and neuroinflammation. Biomolecule-target-pathway (B-T-P) networks confirmed the therapeutic relevance of the identified compounds.
Conclusion
Using a fully computational framework, this study identifies α-santalol and β-eudesmol as promising natural molecules with potential relevance to PD-associated pathways. These results are hypothesis-generating, and future biological validation through neuronal survival assays, oxidative-stress and inflammation models, and LRRK2-related functional studies is warranted.
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