Structure-function relationship between a natural cosmetic active ingredient and the olfactory receptor OR2AT4.

OBJECTIVE: Although the olfactory receptor OR2AT4 was described as involved in epidermal renewal, there is no data about a cosmetic active ingredient activating this receptor. The aim of this research work was thus to identify a natural molecule binding to this receptor in order to stimulate keratinocyte migration. METHODS: For this purpose, natural molecules were extracted from Cocos nucifera flour. Then, efficacy of this natural extract was evaluated on keratinocyte migration in vitro. Molecules of the Cocos nucifera flour extract were then identified by UPLC-MS/MS. Molecular docking was finally conducted to investigate the potential interaction between identified molecules and the olfactory receptor OR2AT4. RESULTS: The Cocos nucifera flour extract significantly increased keratinocyte migration and results demonstrated that this effect was mediated by the olfactory receptor OR2AT4. Metabolomic analysis revealed two molecules, nonioside D and butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, as significantly present in the Cocos nucifera flour extract compared to both Cocos nucifera oil and water. Finally, molecular docking revealed that butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside could interact with the extracellular domain 2 of the OR2AT4. CONCLUSION: This study highlighted for the first time a natural molecule, extracted from Cocos nucifera flour, able to interact with the olfactory receptor OR2AT4 and promote the keratinocyte migration and thus the epithelialization.

OBJECTIF: Bien que le récepteur olfactif OR2AT4 a été décrit comme étant impliqué dans le renouvellement de l'épiderme, il n'y a à ce jour aucune donnée concernant un ingrédient actif cosmétique activant ce récepteur. Le but de cette étude est donc d'identifier une molécule naturelle capable de se fixer au récepteur OR2AT4 afin de stimuler la migration des kératinocytes. METHODE: L'efficacité de cet extrait naturel sur la migration des kératinocytes in vitro a ensuite été évaluée. Les molécules présentes dans l'extrait de farine de Cocos nucifera ont ensuite été identifées par UPLC-MS/MS. Enfin, des expérimentations de docking moléculaire ont été réalisées afin d'identifier une potentielle interaction entre les molécules précédemment identifiées et le récepteur olfactif OR2AT4. RESULTATS: L'extrait de farine de Cocos nucifera augmente significativement la migration des kératinocytes via l'activation du récepteur olfactif OR2AT4. Les analyses métabolomiques ont révélées deux molécules, le nonioside D et le butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, comme étant significativement présentes dans l'extrait de farine de Cocos nucifera en comparaison avec l'huile et l'eau de coco. Enfin, le docking moléculaire révèle que le butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, présent dans l'extrait de farine de Cocos nucifera peut interagir avec le domaine extracellulaire 2 du récepteur olfactif OR2AT4. CONCLUSION: Cette étude a identifié pour la première fois une molécule naturelle, extraite de la farine de Cocos nucifera, capable d'interagir avec le récepteur olfactif OR2AT4, afin de stimuler la migration kératinocytaire et ainsi favoriser le processus de ré-épithélialisation.

Lipid organization in xerosis: the key of the problem?

OBJECTIVE: Although xerosis is a common skin disorder among the population, there is no in vivo global study focusing on xerotic skin. Hence, the objective of this study was to characterize xerotic skin from the surface to the molecular scale with in vivo and non-invasive approaches. METHODS: For this purpose, 15 healthy volunteers with normal skin and 19 healthy volunteers with xerotic skin were selected by a dermatologist, thanks to a visual scorage. Firstly, the skin surface was characterized with biometric measurements. Then, the state of skin dryness was assessed by in vivo confocal microscopy. The molecular signature of xerotic skin was then determined by in vivo confocal Raman microspectroscopy. Finally, an identification of stratum corneum (SC) lipids was performed using Normal phase liquid chromatography (NP-LC) coupled to two detectors: Corona and High Resolution/Mass Spectroscopy (HR/MS). RESULTS: Results obtained at the skin surface displayed an increase in the transepidermal water loss (TEWL) and a decrease in the hydration rate in xerotic skin. Confocal microscopy revealed an alteration of the cell shape in xerotic skin. Moreover, confocal Raman microspectroscopy demonstrated directly in vivo and non-invasively the lack of organization and conformation of lipids in this skin. Finally, HPLC analyses revealed that the three ceramide sub-classes (NdS, NS and EOP) significantly decrease in xerosis. Altogether, these results identify parameters for the characterization of xerotic skin compared to normal. CONCLUSION: This study highlighted discriminative parameters from the surface to the molecular level in vivo and non-invasively between xerotic and normal skins. These results will be useful for the development of new cosmetic active ingredients dedicated to xerotic skin.