HS-SPME-GC-MS-Based Network Pharmacology Analysis of Major Natural Products in Panax ginseng Hydrosol

Panax ginseng hydrosol, a water-distilled coproduct of ginseng extraction, contains diverse volatile and semi-volatile terpenoids beyond the well-studied ginsenosides. We applied HS-SPME-GC-MS semiquantitative analysis-based network pharmacology approach to systematically characterize the multi-target and multi-pathway potential of 30 principal hydrosol constituents. In silico target prediction (BATMAN-TCM) identified 78 human protein targets, which were integrated with high-confidence protein-protein interactions. Ginsenol is the main volatile component in Panax ginseng hydrosol, followed by sandaracopimarinol, (+)-spathulenol, (-)-spathulenol, isospathulenol, (+)-cycloisolongifol-5-ol, and rosifoliol. Minor components include monoterpenes such as alpha-terpineol and menthol, alcohols, ketones, and hydrocarbons like (-)-globulol and ferruginol. For the top 5 diseases and indications, most strongly supported as target gene explanations based on main components and robust database-backed evidence, pain modulation, neurodegenerative diseases, breast cancer, androgen receptor-related disorders, and autoimmune-metabolic genetic disorders emerge as leading categories. These findings validate a multicomponent, multi-target mechanism underlying Panax ginseng hydrosol's traditional uses and highlight synergistic interactions that extend the pharmacological landscape beyond ginsenoside-centric models. Our study provides a molecular framework for future experimental validation and rational development of hydrosol-based therapeutics.