Indirect Skin Homeostasis Modulation by an Essential Oil Blend in Mice with Insomnia Comorbid Anxiety: Sensitivity of Dermal Fibroblasts to Exogenously Applied Circulating Molecules

Background/Objectives: Studies have confirmed that essential oils extracted from aromatic plants exert mood-regulating and skin-beneficial effects. Although the concept of “emotional skincare” has attracted growing research interest, experimental evidence supporting the indirect skin-protective effects of essential oils through emotional regulation remains limited. This study investigates the indirect effect of an essential oil blend (EOB) on skin homeostasis in mice with insomnia comorbid anxiety (ICA, a pharmacologically validated emotional stress model induced by para-chlorophenylalanine) and aims to profile the sensitivity of dermal fibroblasts to candidate circulating molecules identified from EOB-treated ICA mice, thereby laying a mechanistic foundation for emotional skincare research. Methods: An essential oil blend (EOB) comprising lavender, Kushui rose, sweet orange, Roman chamomile, sandalwood, and clary sage essential oils was prepared. An ICA mouse model was established using para-chlorophenylalanine. Behavioral phenotypes, as well as neurotransmitter and hormonal indices, were measured to validate the anxiolytic and sleep disturbance-alleviating effects of EOB administered via intraperitoneal injection at 300 mg/kg per injection (two injections overall). Skin histological alterations and circulating biomarker profiles were evaluated, and selected differentially altered circulating molecules were exogenously applied to cultured dermal fibroblasts in vitro to assess their effects on fibroblast functions. Results: EOB significantly alleviated ICA-like behaviors and ameliorated abnormal levels of brain neurotransmitters and hormones in mice. Although only mild histological variations were observed in the skin after EOB intervention, significant alterations in cortisol, melatonin, 5-hydroxytryptamine, interleukin-10, and type I collagen were detected in serum or skin tissues. Exogenous application of these circulating molecules elicited differential responses in dermal fibroblasts, affecting oxidative stress, inflammatory responses, and extracellular matrix synthesis in a molecule-specific manner. Notably, these fibroblast assays only demonstrate cellular sensitivity in vitro and do not prove that these circulating molecules directly mediate the in vivo effects observed in mice. Conclusions: EOB intervention ameliorates insomnia- and anxiety-related behaviors and concurrent favorable changes in skin-associated molecular profiles in ICA mice. These changes are accompanied by alterations in circulating bioactive molecules to which dermal fibroblasts exhibit measurable sensitivity in vitro. These observations are consistent with, but do not definitively establish, a brain–skin axis-mediated mechanism. These findings provide preliminary experimental evidence for the emotional skincare concept and identify candidate circulating molecules for future causal validation; the in vivo regulatory roles of these molecules and the precise signaling pathways involved remain to be established in dedicated mechanistic studies.