Trihydroxybenzoic acid glucoside as a global skin color modulator and photo-protectant

Hanane Chajra,1 Gérard Redziniak,2 Daniel Auriol,3 Kuno Schweikert,1 Fabrice Lefevre1 1Induchem AG, Volkestwil, Switzerland; 2Cosmetic Invention, Antony, 3Libragen SA, Toulouse, France Background: 3,4,5-Trihydroxybenzoic acid glucoside (THBG), a molecule produced by an original biocatalysis-based technology, was assessed in this study with respect to its skin photoprotective capacity and its skin color control property on Asian-type skin at a clinical level and on skin explant culture models. Methods: The double-blinded clinical study was done in comparison to a vehicle by the determination of objective color parameters thanks to recognized quantitative and qualitative analysis tools, including Chroma-Meter, VISIA-CR™, and SIAscope™. Determination of L* (brightness), a* and b* (green–red and blue–yellow chromaticity coordinates), individual typology angle, and C* (chroma) and h* (hue angle) parameters using a Chroma-Meter demonstrated that THBG is able to modify skin color while quantification of ultraviolet (UV) spots by VISIA-CR™ confirmed its photoprotective effect. The mechanism of action of THBG molecule was determined using explant skin culture model coupled to histological analysis (epidermis melanin content staining). Results: We have demonstrated that THBG was able to modulate significantly several critical parameters involved in skin color control such as L* (brightness), a* (redness), individual typology angle (pigmentation), and hue angle (yellowness in this study), whereas no modification occurs on b* and C* parameters. We have demonstrated using histological staining that THBG decrease epidermis melanin content under unirradiated and irradiated condition. We also confirmed that THBG molecule is not a sunscreen agent. Conclusion: This study demonstrated that THBG controls skin tone via the inhibition of melanin synthesis as well as the modulation of skin brightness, yellowness, and redness. Keywords: skin color, UV spots, pigmentation, sun damage, melanin&nbsp

Combination of new multifunctional molecules for erythematotelangiectatic rosacea disorder

Hanane Chajra,1 Mahdi Nadim,2 Daniel Auriol,3 Kuno Schweikert,1 Fabrice Lefevre1 1Induchem AG, Volkestwil, Switzerland; 2CBM-CNRS, Orléans Cedex, 3Libragen SA, Toulouse, France Background: Rosacea, a common chronic skin disorder, is currently managed by patient education, pharmacological drugs, medical devices (laser and light therapies), and use of proper skin cares. Unfortunately, none of these actual treatments used alone or in combination is curative, and so we proposed a dermocosmetic active ingredient to mitigate some aspects of the rosacea and particularly for erythematotelangiectatic rosacea. Methods: Dermocosmetic active ingredient is composed of three glucosylated derivatives of natural plants hydroxybenzoic acid and hydroxycinnamic acids (rosmarinic acid, gallic acid, and caffeic acid). Anti-inflammatory, anti-angiogenesis, and anti-degranulation studies were done on cellular models (keratinocytes, mast cells, and endothelial cells). Efficiency of the active ingredient in comparison to placebo was assessed clinically on human volunteers having erythematotelangiectatic rosacea. The active and placebo were applied topically twice a day for 28 days. Biometrical analyses were done using a siascope tool. Results: We found that the active ingredient decreases inflammation (inhibition of interleukin-8 and tumor necrosis factor release), decreases degranulation of mast cells (inhibition of histamine release), and controls angiogenesis mechanism (inhibition of the production of vascular endothelial growth factor and neovessel formation) on cellular models. Study on human volunteers confirmed macroscopically the efficiency of this active ingredient, as we observed no neovessel formation and less visible vessels. Conclusion: Although rosacea is a skin condition disorder that is difficult to heal, the studies have shown that this active ingredient could be a dermocosmetic support, especially for erythematotelangiectatic rosacea armamentarium. The active ingredient was topically applied on the face for 28 days and improved erythematotelangiectatic rosacea symptoms either by decreasing them (vessels are less visible) or by limiting their development (any neovessels). The active ingredient decreases inflammation (inhibition of interleukin-8 and tumor necrosis factor release), decreases degranulation of mast cells (inhibition of histamine release), and limits the angiogenesis process (inhibition of vascular endothelial growth factor production and neovessel formation). Keywords: rosacea, erythema, gallic acid, rosmarinic acid, caffeic acid, glucosylatio

Reactivating the extracellular matrix synthesis of sulfated glycosaminoglycans and proteoglycans to improve the human skin aspect and its mechanical properties

Hanane Chajra,1 Daniel Auriol,1 Francine Joly,2 Aurélie Pagnon,3 Magda Rodrigues,4 Sophie Allart,4 Gérard Redziniak,5 Fabrice Lefevre1 1Libragen, Induchem (Givaudan Active Beauty), Toulouse, 2Sephra Pharma, Puteaux, 3Novotec, Bron, 4Centre de Physiopathologie de Toulouse-Purpan, Toulouse, 5Cosmetic Inventions, Antony, France Background: The aim of this study was to demonstrate that a defined cosmetic composition is able to induce an increase in the production of sulfated glycosaminoglycans (sGAGs) and/or proteoglycans and finally to demonstrate that the composition, through its combined action of enzyme production and synthesis of macromolecules, modulates organization and skin surface aspect with a benefit in antiaging applications. Materials and methods: Gene expression was studied by quantitative reverse transcription polymerase chain reaction using normal human dermal fibroblasts isolated from a 45-year-old donor skin dermis. De novo synthesis of sGAGs and proteoglycans was determined using Blyscan™ assay and/or immunohistochemical techniques. These studies were performed on normal human dermal fibroblasts (41- and 62-year-old donors) and on human skin explants. Dermis organization was studied either ex vivo on skin explants using bi-photon microscopy and transmission electron microscopy or directly in vivo on human volunteers by ultrasound technique. Skin surface modification was investigated in vivo using silicone replicas coupled with macrophotography, and the mechanical properties of the skin were studied using Cutometer. Results: It was first shown that mRNA expression of several genes involved in the synthesis pathway of sGAG was stimulated. An increase in the de novo synthesis of sGAGs was shown at the cellular level despite the age of cells, and this phenomenon was clearly related to the previously observed stimulation of mRNA expression of genes. An increase in the expression of the corresponding core protein of decorin, perlecan, and versican and a stimulation of their respective sGAGs, such as chondroitin sulfate and heparan sulfate, were found on skin explants. The biosynthesis of macromolecules seems to be correlated at the microscopic level to a better organization and quality of the dermis, with collagen fibrils having homogenous diameters. The dermis seems to be compacted as observed on images obtained by two-photon microscopy and ultrasound imaging. At the macroscopic level, this dermis organization shows a smoothed profile similar to a younger skin, with improved mechanical properties such as firmess. Conclusion: The obtained results demonstrate that the defined cosmetic composition induces the synthesis of sGAGs and proteoglycans, which contributes to the overall dermal reorganization. This activity in the dermis in turn impacts the surface and mechanical properties of the skin. Keywords: cosmetic composition, decorin, dermis, polysaccharid

The effect of Ethylene Oxide Sterilisation, Beta Irradiation and Gamma Irradiation on Collagen Fibril-Based Scaffolds.

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BMP-2, hypoxia, and COL1A1/HtrA1 siRNAs favor neo-cartilage hyaline matrix formation in chondrocytes

cited By 10International audienceOsteoarthritis (OA) is an irreversible pathology that causes a decrease in articular cartilage thickness, leading finally to the complete degradation of the affected joint. The low spontaneous repair capacity of cartilage prevents any restoration of the joint surface, making OA a major public health issue. Here, we developed an innovative combination of treatment conditions to improve the human chondrocyte phenotype before autologous chondrocyte implantation. First, we seeded human dedifferentiated chondrocytes into a collagen sponge as a scaffold, cultured them in hypoxia in the presence of a bone morphogenetic protein (BMP), BMP-2, and transfected them with small interfering RNAs targeting two markers overexpressed in OA dedifferentiated chondrocytes, that is, type I collagen and/or HtrA1 serine protease. This strategy significantly decreased mRNA and protein expression of type I collagen and HtrA1, and led to an improvement in the chondrocyte phenotype index of differentiation. The effectiveness of our in vitro culture process was also demonstrated in the nude mouse model in vivo after subcutaneous implantation. We, thus, provide here a new protocol able to favor human hyaline chondrocyte phenotype in primarily dedifferentiated cells, both in vitro and in vivo. Our study also offers an innovative strategy for chondrocyte redifferentiation and opens new opportunities for developing therapeutic targets. Copyright 2015, Mary Ann Liebert, Inc