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New Insights in the Biodegradability and the Ecotoxicological Effects of Solar Products Containing Mineral and Chemical UV-Filters on Marine Zoo- and Phytoplanktons: An in silico and in vitro Study

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Journal of Cosmetics, Dermatological Sciences and Applications 2024年第1期14卷 98-111页

作者： Jean-Claude Hubaud Karim Mekideche Jean-Eric Branka luc lefeuvre HELIOSCIENCE Cité de la cosmétique 2 rue Odette Jasse Marseille France EPHYSCIENCE 498ter route de Saint Joseph de Porterie Nantes France Laboratoires Dermatologiques d’Uriage Neuilly-sur-Seine France

Background: Cosmetic formulations, and particularly solar products which contain mineral and chemical UV-filters, are often suspected of causing harmful effects on marine fauna and flora. After the publication of our work in 2019 concerning the ecotoxicological effects of such formulations on corals (Seriatopora hystrix), we here provide some new information about the biodegradability and the ecotoxicological effects of these products on marine zoo- and phytoplankton. Therefore, we choose to realize in silico and in vitro studies of the biodegradability of several solar products but also to evaluate the ecotoxicological effects of these products on one phytoplankton, i.e. Phaeodactylum tricornutum, and one zooplankton, i.e. Acartia tonsa, of a great importance for sea species survival (notably as sources of food). Materials and methods: Two different approaches were used to study the biodegradability of the tested products: One in silico method and an in vitro one. 2 solar products were involved in the in silico study which consisted in the determination of the degradation factor (DF) of each ingredient of the tested formulas in order to finally obtain their estimated biodegradability percentage. Already available data concerning each ingredient coupled to a computer model developed with one of our partners were used to achieve this study. The in vitro study involved 8 formulas containing UV-filters and was led by following the OECD 301 F guidelines. Ecotoxicological studies of 7 of the formulas containing UV-filters were for their part realized by following the ISO 10253 guidelines for the experiments led with Phaeodactylum tricornutum, and the ISO 14669 guidelines for the experiments led with Acartia tonsa. In these studies, the effect of each tested product on crustaceans’ mortality and algal growth inhibition was assessed. Results: The in silico study predicted that formulas containing chemical UV-filters display a high biodegradability (superior to the threshol

关键词： UV-Filters Chemical UV-Filter Biodegradability Ecotoxicology in silico in vitro Zooplankton Phytoplankton Phaeodactylum tricornutum Acartia tonsa

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TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation： pro-inflammatory response induced by their activation and their sensitization

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Protein & Cell 2017年第9期8卷 644-661页

作者： Olivier Gouin Killian L'Herondelle Nicolas Lebonvallet Christelle Le Gall-lanotto Mehdi Sakka Virginie Buhe Emmanuelle PIee-Gautier Jean-luc Carre luc lefeuvre Laurent Misery~,Raphaele Le Garrec Laboratory on Interaction Neurons-Keratinocytes (LINK) University of Western Brittany 29200 Brest France Uriage Dermatological Laboratories 92400 Courbevoie France

Cutaneous neurogenic inflammation （CNI） is inflammation that is induced （or enhanced） in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 （TRPV1 and TRPA1, respectively） are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neu- ronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.

关键词： sensory nervenflammation inflammatory geneneurogenic skinregulation pruritus

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Thermal Water from Uriage-les-Bains Exerts DNA Protection, Induction of Catalase Activity and Claudin-6 Expression on UV Irradiated Human Skin in Addition to Its Own Antioxidant Properties

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Journal of Cosmetics, Dermatological Sciences and Applications 2014年第2期4卷 99-106页

作者： Francine Joly Jean-Eric Branka luc lefeuvre EPHYSCIENCE Nantes France Laboratoire SEPhRAPHARMA Puteaux France Laboratoires Dermatologiques d’Uriage Neuilly sur Seine France

Aim: In order to decipher the mechanisms underlying the known protective effects of the thermal water from Uriage-les-Bains (TWFULB) on the skin barrier function, we studied its antioxidant properties as well as its effect on the expression of the tight-junctional protein claudin-6, a candidate tumor suppressor factor. Study Design/Methods: In a first step, TBARS and SOD activity assays were performed in an in vitro model of human dermal fibroblasts treated by hypoxanthine/xanthine oxidase (HO/XO) mixture, in order to evaluate the own antioxidant effect of the thermal water. In a second step, human keratinocytes irradiated or not by UVB were used to evaluate the protective role of TWFULB on nuclear DNA damage using a comet assay. In a third step, an ex vivo model of human skin explants irradiated or not by UVA and UVB was used to evaluate the effect of TWFULB on the intracellular catalase activity and on the cutaneous claudin-6 expression. Results: TWFULB showed significant protective effects against oxidative stress induced by HO/XO: the cell viability was improved and the lipid peroxidation was reduced. The tested thermal water also showed significant SOD-like activity and protective effect on the UVB-stressed DNA. Considering the ex vivo models of skin explants, TWFULB was able to counterbalance the “negative” effect of UVB on the intracellular catalase activity and on the cutaneous claudin-6 ***: This multiparametric approach shows the antioxidant activity of TWFULB and emphasizes its role in the DNA protection of the cutaneous tissue in front of the UV irradiations, and finally suggests that some effects could involve the candidate suppressor functions of claudin-6.

关键词： Human Skin UVA-UVB Thermal Water from Uriage-les-Bains Claudin-6 Antioxidant Effect SOD-Like Effect Catalase

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Modulation of Sodium-Dependent Transporters Expression in Normal Human Keratinocytes by a Sodium Rich Isotonic Thermal Water

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Journal of Cosmetics, Dermatological Sciences and Applications 2012年第4期2卷 254-262页

作者： Clotilde Verdy Jean-Eric Branka luc lefeuvre Effiscience Immeuble Bio Ouest Nantes France Laboratoires Dermatologiques d’Uriage Siège Social Courbevoie France

Background/Aim: In order to show that water can participate to the skin defense in front of different stress, we investigated the effect of an isotonic thermal water notably rich in Sodium (i.e. the Uriage thermal water) on 1) The taurine transporter (TauT) expression in human normal keratinocytes irradiated or not by UVB;and 2) the Sodium-dependent vitamin C transporter 1 (SVCT1) expression in human normal keratinocytes issued from two “young” and two “aged” subjects, irradiated or not by UVB. Methods and Results: Using sensible and specific TAUT and SVCT1 ELISA assays developed in house, we provide 1) the unambiguous demonstration that the Uriage thermal water is able to help the epidermis to maintain its taurine content under UVB irradiation;2) the first example of an altered SVCT1 expression in “aged” keratinocytes and of a significant positive effect of the Uriage thermal water on this altered SVCT1 production;and 3) arguments showing that Uriage thermal water is also able to participate to the regulation of the SVCT1 production in UVB-irradiated keratinocytes. Conclusion: Taking together, these results suggest that the Uriage thermal water could act to efficiently protect the skin from dehydration through its effect on TauT and SVCT1 expression, and furthermore, to allow a more efficient taurine and ascorbic acid supplying to the epidermis in order to protect him from other aggressions such as oxidant stress for example.

关键词： TauT SVCT1 Thermal Water Young and Aged Keratinocytes UVB

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Telomere Protective Effects of a Cyanobacteria Phycocyanin against Blue Light and UV Irradiations: A Skin Anti-Aging and Photo-Protective Agent

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Journal of Cosmetics, Dermatological Sciences and Applications 2019年第4期9卷 336-345页

作者： Francine Joly Jean-Eric Branka Eric Darnis luc lefeuvre Sephra 87 rue Voltaire Puteaux France Ephyscience 21 rue La Noue Bras de Fer Nantes France Gynecology-Obstetrics Hospital “Mère et Enfant” Nantes France Laboratoires Dermatologiques d’Uriage Neuilly-sur-Seine France

Background: Cyanobacteria phycocyanins (Cps) have already shown powerful antioxidant properties. In human cells submitted to oxidative stress the telomeres length decrease, the expression of progerin and the activity of mTOR are increased. At our knowledge, there is no published data on Cps correlated with ultraviolet radiation (UV) and blue light effects in human cells regarding telomeres’ length, progerin expression or mTOR1 complex activity. Objectives: In this study, we sought to assess 1) telomeres’ length in newborn human fibroblasts exposed to UV and blue light;2) progerin production in mature human normal fibroblasts exposed to UV;3) mTOR1 activation in adult human normal keratinocytes exposed to UV, analyzing the activity of a Cyanobacteria phycocyanin (Cp) in these in vitro models. Materials and Methods: Human skin fibroblasts or human normal keratinocytes were cultured—in the absence or in the presence of Cp and submitted to UVB + UVA and blue light irradiations. Telomeres’ length, progerin expression and mTOR1 activity were then assessed by molecular biology and immuno-enzymatic methods. Results: In cultured fibroblasts exposed to irradiations and treated by Cp, telomeres’ shortage and progerin expression were lower compared to irradiated untreated cells. In cultured keratinocytes treated by Cp and exposed to irradiations, the mTOR activity was lower compared to irradiated untreated cells. Conclusions: In these in vitro studies on human skin fibroblasts and on normal human keratinocytes, the cyanobacteria phycocyanin (Cp) showed a decrease of damages induced by UV and blue light expressed by telomeres preservation and downregulation of progerin expression and of mTOR activity, thus showing skin anti-aging and photo-protective potential.

关键词： Cyanobacteria Phycocyanins UVA UVB Blue Light Telomere Length Telomere Shortage Progerin Production mTOR1 Activity Human Skin Cells Aging/Photo-Aging

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Beneficial Effect of a Thermal Spring Water on the Skin Barrier Recovery after Injury: Evidence for Claudin-6 Expression in Human Skin

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Journal of Cosmetics, Dermatological Sciences and Applications 2012年第4期2卷 273-276页

作者： Francine Joly Cécile Gardille Eric Barbieux luc lefeuvre Laboratoire SEPhRAPHARMA Puteaux France Laboratoires Dermatologiques d’Uriage Siège Social Courbevoie France

Aim: To evaluate the possible advantages of dermo-cosmetic products formulated with thermal spring water instead of deionized water. We studied the effect of a dermo-cosmetic product on skin barrier recovery after injury. In one test the product was formulated with de-ionized water and again using the identical product formulated with thermal spring water. Study Design/Methods: Stratum corneum of human skin explants was removed (and not removed for the control) with an ether/acetone mixture. A cosmetic product, either formulated with de-ionized or thermal spring water, was then topically applied on the explants. After a 5-day incubation period, epidermal expression of aquaporine-3, filaggrin, claudin-4 and claudin-6 was studied by using immunohistochemical techniques. Results: The formulation containing de-ionized water seemed to act on the epidermal expression of filaggrin and claudin-4. When thermal spring water was used to make the formulation, we noted that this expression was greatly enhanced. The formulation containing thermal spring water also acted to increase aquaporin-3 and claudin-6 expression. Conclusion: The use of thermal spring water in cosmetic formulations would appear to contribute to the cosmetic product’s efficacy. It was also interesting to note that this study revealed claudin-6 expression in human skin for the first time.

关键词： Keratinocyte Differentiation Thermal Spring Water Barrier Repair Claudin-4 Claudin-6 Aquaporine 3 Filaggrin

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Effect of a Thermal Spring Water on Carbohydrate-Protein Interactions in In-Vitro Models Implicating Normal Human Keratinocytes and Recombinant Lectins

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Journal of Cosmetics, Dermatological Sciences and Applications 2023年第4期13卷 269-276页

作者： Benoît Roubinet Ludovic Landemarre Karim Mekideche Jean-Eric Branka luc lefeuvre GLYcoDiag 2 rue du cristal Orléans France EPHYSCIENCE 498ter route de Saint Joseph de Porterie Nantes France Laboratoires Dermatologiques d’Uriage Neuilly-sur-Seine France

Background: Sugar moiety of macromolecules is today very well known for its implications in many biological recognition mechanisms including cell-cell, extracellular matrix-cell and/or bacteria-cell interactions. In this context lectins, which are carbohydrate-binding proteins displaying a high affinity for sugar groups of other molecules, are of a great importance, notably in immune response involving bacteria, viruses and fungi. As protein-carbohydrate interactions are often mediated by ions such as calcium, zinc or magnesium, we were prompted to study the effect of a thermal spring water (which contains this type of component) on interactions existing between: 1) osidic receptors of human normal keratinocytes and 2) two lectins greatly implicated in the immune response mechanisms (i.e. the dectin-1 and the langerin), and their ligands. Materials and Methods: In a first series of experiments, we studied the effect of increasing concentrations of a thermal spring water on interactions existing between glycosylated molecules and the osidic receptors expressed at the normal human keratinocytes surface. In a second step, and in order to better understand the putative effect of our thermal spring water on the immune response, we analyzed its effect on the interactions existing between the dectin-1 (implicated in the recognition of bacteria, viruses and fungi) and the langerin (expressed by Langerhans cells, the immune cells of the cutaneous tissue), and their ligands in a model using recombinant human lectins and appropriate binding molecules. Results: We showed here that our thermal spring water was able to reinforce interactions between keratinocytes osidic receptors and some of their ligands, in a dose-related manner: From 8% to 55% of increase with 10% to 30% (v/v) of thermal spring water. In the second part of our studies, we also showed that our thermal spring water was able to modulate interactions between dectin-1 and langerin and their ligands through a biphas

关键词： Carbohydrate-Protein Interaction Lectin Dectin-1 Langerin Normal Human Keratinocytes Immune System

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Ecotoxicological Effects of Cosmetic Formulas Containing Chemical and Mineral UV Filters on Seriatopora hystrix Fragments

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Journal of Cosmetics, Dermatological Sciences and Applications 2019年第3期9卷 228-234页

作者： Marius Anton Ionescu Marius Anton Ionescu Catherine Le Breton Jean-Claude Hubaud Jean-Eric Branka luc lefeuvre Laboratoires Dermatologiques d’Uriage Neuilly-sur-Seine France Dermatology University Hospital “Saint-Louis” Paris France Helioscience Marseille France Ephyscience Nantes France

Background: Over the last few years sunscreen products have been suspected to be harmful to corals, especially because of their putative negative impact on symbiotic microalgae housed by these cnidarians. Previous publications reported that minerals or chemical UV filters could induce the release of microalgae from corals inducing their bleaching. The study of the ecotoxicity of finished cosmetic products containing these filters is important. Objectives: We sought to assess ex vivo the toxicity of five emulsions containing UV-filters on coral cuttings of Seriatopora hystrix. Materials and Methods: Coral cuttings were put in contact with 5 different emulsions containing UV-filters. The toxicity readout was the ability to induce polyp retraction and/or fragment bleaching of the coral cuttings of Seriatopora hystrix. Results: In our experimental conditions, none of the five tested formulas neither induced any significant polyp retraction nor triggered fragment bleaching of the coral. Conclusions: The five tested emulsions containing UV-filters did not modify coral cuttings. In vivo, larger tests are necessary to verify the results of this ex vivo pilot study.

关键词： Sunscreens Chemical UV Filters Mineral UV Filters Coral Polyp Retraction Coral Bleaching Seriatopora hystrix Ecotoxicology

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<i>In Vitro</i>and <i>in Vivo</i>Anti-Inflammatory Effect of a Biotechnologically Modified Borage Seed Extract: Evidence for Lipid Pro-Resolving Mediators’ Implication in the Enhancement of Psoriatic and Atopic Dermatitis Lesions

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Journal of Cosmetics, Dermatological Sciences and Applications 2015年第2期5卷 151-160页

作者： Gérald Chene Vincent Baillif Emeline Van Goethem Jean-Eric Branka Toni Ionescu Géraldine Robert luc lefeuvre Ambiotis SAS Cana Biotech 2 Toulouse France EPHYSCIENCE Nantes France Laboratoires Dermatologiques d’Uriage Siège Social Courbevoie France

Aim: Resolvins, maresins and lipoxins are lipid mediators issued from essential polyunsaturated fatty acids which are the first anti-inflammatory and pro-resolving signals identified during the resolution phase of inflammation. As borage oil and/or borage seed extracts have shown beneficial action in treatment of atopic dermatitis or eczema in human and canine, we have modified a borage oil component by using biotechnology in order to get a compound structurally related to a polyunsaturated fatty acid, and we have studied its ability to reduce inflammation mediators production through the generation of resolvins, maresins and/or lipoxins. Additionally, we have demonstrated the potent anti-inflammatory effect of this new compound which consists in borage seed oil aminopropanediol amides, through an in vivo study concerning subjects suffering from psoriasis or atopic dermatitis. Study Design/Methods: For the in vitro study, inflammation was induced in co-cultures of human dendritic cells and normal keratinocytes by the addition of PMA and the calcium ionophore A23187. Ability of our borage seed oil aminopropanediol amides to increase resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis was then measured. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8) and PGE2 productions were also quantified. For the in vivo study, 36 subjects suffering from psoriasis or atopic dermatitis have used twice a day during 30 days, a formulation containing borage seed oil aminopropanediol amides. Before the beginning of the study and after 30 days’ treatment, the severity of psoriasis and of atopic dermatitis was evaluated by using the PGA and the SCORAD scoring scales, respectively. Results: Borage seed oil aminopropanediol amides were able to significantly increase the resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis. Concomitantly, they were also able to significantly inhibit the production of IL-1β, IL-6, IL-8 and PGE2 induced by the PMA and the calcium ionophore A23187 in the

关键词： Human Skin Biotechnologically Modified Borage Extract Interleukins Inflammation Psoriasis Atopic Dermatitis Resolvins Maresins Lipoxins

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