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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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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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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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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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New Insights in the Skin Protective Activity of a Dexpanthenol Containing Formula (BEPANTHEN®) in a Diaper Rash-Like Model

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Journal of Cosmetics, Dermatological Sciences and Applications 2020年第2期10卷 76-84页

作者： Erwan Peltier Karim Mekideche jean-eric branka Sonja Trapp Bayer Consumer Care AG Research & Development Consumer Health Medical Category Dermatology Basel Switzerland Ephyscience Nantes France

Background: Dexpanthenol containing formula (BEPANTHEN®), formulated as a water in oil preparation, is currently widely marketed as a diaper care product aiming to protect baby’s buttocks and repair diaper dermatitis. Dexpanthenol is a well-known moisturizer with barrier-improving properties and the oily phase of the water in oil preparation forms a lipophilic film on the skin surface that isolates the skin from irritants (feces and urine). Prolonged contact with irritants triggers a local inflammation cascade responsible for the cutaneous erythema. To further investigate the protective properties of skin barrier preparations, we took advantage of an ex vivo model of healthy human skin discs especially designed to evaluate protective and/or repairing effects of topical preparations recommended for baby’s buttocks through the measurement of interleukin-1 alpha release (a cytokine considered as the Primum movens of the skin inflammatory reaction), following the application of different irritants. Methods: Healthy human skin discs have been incubated in the absence (control) or in the presence of two irritants, i.e. a “urine like + urease” preparation and sodium dodecyl sulfate, and in the presence of three ointments, one containing dexpanthenol, but not the other two. At the end of the incubation period, interleukin-1 alpha (IL-1α) was quantified in the explants culture media. Results: “Urine like + urease” preparation (ULU) and sodium dodecyl sulfate (SDS) both increased IL-1α production of skin explants by 181.1% (p α release by 67.42% (p α

关键词： Dexpanthenol BEPANTHEN® Human Skin Protection Interleukin-1 Diaper-Rash

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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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Development of an in Vitro Assay to Evaluate the Biological Impact of 5G Technology on Human Skin—Shield Effect of a Tannin-Rich Plant Extract

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Journal of Cosmetics, Dermatological Sciences and Applications 2022年第2期12卷 100-108页

作者： Katharina Kappler Franziska Wandrey jean-eric branka Stéphane Poigny Fred Zülli Mibelle Group Biochemistry Mibelle AG Buchs Switzerland Ephyscience Nantes France

Background: The new 5G telecommunication technology has stirred concerns about potential negative effects on human health by radiofrequency electromagnetic fields. As to whether skin biology can be affected by 5G waves has remained an unsolved challenge despite recent studies dealing with this issue. In particular, a strategy for rational design of an assay allowing to 1) reproducibly evaluate and decipher the 5G effects on skin as well as 2) test the potential protective effects of cosmetic active ingredients, has yet to be found. Here we describe an in vitro model of human normal keratinocytes irradiated by 5G waves and show their impact on two biomarkers of inflammatory stress, i.e. interleukin-1β (IL-1β) and reactive oxygen species (ROS) production. In addition, the capacity of a tannin-rich plant extract to protect against 5G impact is evaluated. Materials and Methods: In the first series of experiments, monolayers of human normal keratinocytes were irradiated or not (control) by 5G waves (3.5 MHz) in an anechoic chamber and were incubated at 37˚C for 24 hours. At the end of the incubation period, extracellular IL-1β and intracellular ROS were quantified using specific ELISA and colorimetric assays, respectively. In the second series of experiments, the effect of an overnight pre-incubation with increasing concentrations of a tannin-rich plant extract was evaluated. Additionally, we studied in a prospective way the expression of a set of 88 genes selected for their relevance to keratinocyte homeostasis, in relation to the 5G challenge as well as the protective effect of a tannin-rich plant extract. Results: 5G waves significantly increased IL-1β production by 48.4% (p β and ROS production. Finally, the expression of 47 genes was modified by 5G waves and/or by the tannin-rich plant extract. Conclusion: This is to our knowledge the first evaluation of the impact of 5G technology on inflammatory biomarkers of human normal skin cells. Here we provide an innova

关键词： 5G waves Human Normal Keratinocytes Inflammation ROS Interleukin-1 mRNA

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Real Facts about Safety and Efficacy of Zinc Oxide and Titanium Dioxide in Solar Products

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Journal of Cosmetics, Dermatological Sciences and Applications 2021年第3期11卷 253-262页

作者： jean-Claude Hubaud Didier Guerin Morgane Di Salvo jean-eric branka Karim Mekideche Philippe Piccerelle Pr Helioscience Cité de la Cosmétique Marseille France Inavive Lab ZA du val d’Huisne Nogent Le Rotrou France Ephyscience 498 ter Route de Saint Joseph de Porterie Nantes France School of Pharmacy Aix-Marseille University 27 Boulevard Jean Moulin Marseille France

Background: Titanium dioxide and zinc oxide were often criticized over the last decade because of their supposed noxious effects on human health. Moreover, these compounds which are frequently introduced in sunscreen products as UV filter, are sometimes associated with poor UVA protection factors. So, in order to clarify the real efficacy and safety status of these products, we provide here some bibliographic and experimental data regarding 1) their “real” protective effect against UVA rays and 2) their real harmful effects on human skin notably by studying their capability to penetrate through the human cutaneous tissue. Materials and Methods: We studied here 4 sunscreen products containing titanium dioxide and zinc oxide for 3 of them. First, because the UVA-PF values obtained for these compounds by using the “classical” in vitro ISO 24443 procedure seem to be significantly different from to those obtained by using the in vivo method ISO 24442, we chose to develop a new in vitro methodology in order to more precisely define the UVA-PF of titanium and zinc oxides. This new methodology was then used to lead UVA-PF studies with the 4 selected solar products. We also provide here an evaluation of the toxicological effects of titanium and zinc oxides on human skin based on the SCCS reports and analysis of recent and relevant bibliographic studies. Moreover, as the harmful effects of this type of products are closely linked to their ability to penetrate cutaneous tissue, we tested 7 sunscreen products to precise the skin penetration profiles of titanium dioxide and zinc oxide by using human skin explants mounted on Franz cells. Results: We here demonstrated that our new in vitro methodology gave some UVA-PF values very close to those obtained with in vivo methods and we took advantage of it to define more realistic UVA-PF for titanium dioxide and zinc oxide. Additionally, we

关键词： TiO2 ZnO UV-Radiations Human Skin UVA-PF Resorption Cutaneous Penetration Franz Cell New in Vitro Methodology

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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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In Vitroand in VivoAnti-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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