An In Vivo Volabolomic Approach to Evaluate a Volatile-Rich Gardenia jasminoides Formulation with potential application in neuro application fields

The skin functions as a complex sensory and neuroimmunological interface capable of detecting chemical stimuli and transmitting signals to the nervous system through peripheral neural pathways and olfactory-like receptors. This emerging understanding supports the development of neuroactive topical systems designed to modulate physiological and emotional responses through the skin–brain axis. Plant-volatile molecules represent a particularly promising class of bioactive compounds for this purpose. Among them, Gardenia jasminoides contains a rich spectrum of aromatic constituents including monoterpenes, sesquiterpenes and benzoate derivatives that are known to influence sensory perception and emotional regulation. [1] A topical oil-in-water formulation was developed as a model system to explore how formulation microstructure can influence the stability, retention and controlled release of neuroactive plant volatiles. Two oil-in-water cream systems were developed as comparative models: a base cream and a formulation enriched with Gardenia jasminoides extract. To evaluate the influence of the extract on formulation structure and stability, key critical quality attributes (CQAs) were assessed, including pH, density, and conductivity, and droplet size distribution (Mastersizer 3000+) to determine dispersion uniformity. Microstructural organization was examined using optical and polarized-light microscopy, while rheological behavior (Thermo Scientific™HAAKE™ MARS™ iQ Air Rheometer) was analyzed through amplitude and frequency sweep tests to evaluate viscoelastic properties and mechanical stability of the systems at different temperatures. Volatile metabolomic behavior was assessed in vivo using an iAQ-2000 MOS sensor capable of detecting broad-spectrum VOCs as CO₂-equivalent ppm. Volabolomic analysis revealed clear formulation- dependent differences in volatile emission patterns. The Gardenia jasminoides formulation produced a markedly higher and more dynamic volatile profile characterized by an initial burst release followed by sustained emission over prolonged periods. This behavior indicates that the formulation microstructure plays a crucial role in regulating the diffusion of aromatic molecules and in maintaining prolonged interaction between plant-derived volatiles and the cutaneous sensory interface. [2] Overall, the results highlight the importance of formulation design in controlling the delivery of volatile phytochemicals and demonstrate how structured topical systems can serve as carriers of neuroactive molecules that interact with the skin–brain axis. The integration of physicochemical characterization with volabolomic analysis provides a valuable framework for understanding the relationship between formulation architecture, volatile dynamics and neurosensory responses. Such an approach opens new avenues for developing innovative plant- based neuroproducts that enhance sensory experience and holistic well-being through controlled volatile delivery. [3]