Molecular recognition and protein interaction mechanisms of volatile organic compounds from Cornus officinalis leaves: a network pharmacology and multiscale validation study centered on β-ionone.

Background: This study investigated the pharmacological potential of volatile organic compounds (VOCs) extracted from the leaves of Cornus officinalis, with the aim of elucidating their interactions with human olfactory receptors and transport proteins, and assessing their applicability in functional foods and aroma-based therapies. Using solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS), 22 representative VOCs were identified from age-stratified samples. Seven small bioactive molecules were selected for integrated analysis involving absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction, network pharmacology, molecular docking, and spectroscopic validation. Network pharmacology analysis identified 243 predicted targets, with β-ionone emerging as a key compound interacting with multiple olfactory receptors - olfactory receptor 1A1 (OR1A1), olfactory receptor 2W1 (OR2W1), and olfactory receptor 10S1 (OR10S1) - as well as transport proteins including human serum albumin (HSA), α-lactalbumin (α-La), and β-lactoglobulin (β-LG).

Results: Functional enrichment analysis highlighted that β-ionone-related targets were involved significantly in olfactory transduction, cytochrome P450 metabolism, and neuroactive ligand-receptor interaction pathways. Molecular docking demonstrated the highest binding affinities for β-ionone across multiple protein classes, which was further validated by fluorescence and ultraviolet-visible (UV-visible) spectroscopy. Thermodynamic analysis confirmed that the binding process was spontaneous, mainly driven by hydrophobic and electrostatic forces. The novel contribution of this study lies in its systematic investigation of C. officinalis leaf VOCs and their interactions with human olfactory and transport proteins, an area not previously explored.

Conclusion: This study elucidated the mechanisms of VOC-protein interactions and highlighted their potential applications in functional foods and aroma therapies. The integrated computational and experimental approach established a solid scientific basis for future screening of natural bioactive compounds with high bioavailability and sensory modulation potential. © 2025 Society of Chemical Industry.