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ABSTRACT Objective Skin xerosis and xerostomia are partially associated with decreased expression and molecular activity of aquaporins 3 and 5 types (AQP3 and AQP5) in skin epidermal cells. While cosmetic occlusive agents and emollients are effective in improving symptoms of skin dryness, maintaining intensive water transport and physiological mechanisms of hydration is also crucial for long‐term skin health. This study aimed to investigate novel skin benefits of caryophyllene (CP) from Eugenia caryophyllata leaves by regulation of AQP3 and AQP5 in human keratinocytes and its preliminary dermatological safety. Methods Various experimental techniques, including MTT assay (cell viability) and ELISA analysis, were used to assess the molecular mechanisms of skin hydration effects of CP individually and in the cosmeceutical formulation on human keratinocytes. The quantitative and qualitative analysis of CP was performed using gas chromatography–mass spectrometry (GC–MS). Affinity scores and targeted action of CP were predicted using a complex of molecular modeling of DiffDock with GNINA, molecular dynamics, and MM/PBSA analysis. To evaluate dermatological tolerance and allergenic potential, the clinical semi‐occlusive patch test of the cosmeceutical formulation containing CP was used. Results According to the cell viability assay, CP showed a good cytotoxicity profile in a concentration range from 0.001 to 0.03 mg/mL on HaCaT keratinocytes, despite being a concentrated substance with polypharmacological activities on skin. The CP in a concentration of 0.01 mg/mL promoted an increase of AQP3 and AQP5 in skin keratinocytes by 99.97% and 332.26%, respectively, compared to basal control ( p < 0.01). Its effect was comparable to that of the Aloe barbadensis leaf extract at 2.5 mg/mL on AQP5, with an increase of 345.24% ( p < 0.01). Moreover, the cosmeceutical formulation with CP in a concentration of 0.1 mg/mL was able to increase AQP3 amount by 100.15% in HaCaT keratinocytes, confirming promising skin hydration potential. It was clinically confirmed that the formulations with CP revealed good dermatological tolerance without negative skin reactions on the group of healthy volunteers. Conclusion CP exerts promising hydration benefits through AQP3 and AQP5 modulation in keratinocytes in vitro and could be safely used in cosmetic formulations. These findings support application as a novel phytochemical for skin and oral conditions, while underscoring the need for further clinical investigation into dermal efficiency and penetration, optimized dosing strategies, and broader biochemical pathways to consider all aspects of use.
Yarovaya et al. (Mon,) studied this question.