High molecular weight hyaluronic acid vectorised with clay provides long-term hydration and reduces skin brightness.

BACKGROUND: Hyaluronic acid (HA) is a widely used active cosmetic ingredient. Its multiple skin care benefits are modulated by its molecular weight. Low molecular weight (LMW) HA can penetrate the skin, but high molecular weight (HMW) HA remains at the surface. Here, we assessed how vectorization of HMW HA with bentonite clay-achieved with an innovative technology-enhances its cosmetic and hydrating properties. MATERIALS AND METHODS: The two HA forms were applied to skin explants; their penetration and smoothing effects were monitored by Raman spectroscopy and scanning electron microscopy. The two forms were biochemically characterised by chromatography, enzyme sensitivity assays, and analysis of Zeta potential. Cosmetics benefits such as, the smoothing effect of vectorised-HA was assessed in ex vivo experiments on skin explants. A placebo-controlled clinical study was finally conducted applying treatments for 28 days to analyse the final benefits in crow's feet area. RESULTS: Raman spectroscopy analysis revealed native HMW HA to accumulate at the surface of skin explants, whereas vectorised HMW HA was detected in deeper skin layers. This innovative vectorisation process changed the zeta potential of vectorised HMW HA, being then more anionic and negative without impacting the biochemical structure of native HA. In terms of cosmetic benefits, following application of vectorised HMW HA ex vivo, the skin's surface was visibly smoother. This smoothing was clinically confirmed, with a significant reduction in fine lines. CONCLUSION: The development of innovative process vectorising HMW HA allowed HMW HA penetration in the skin. This enhanced penetration extends the clinical benefits of this iconic cosmetic ingredient.

Targeting SDF-1 as an efficient strategy to resolve skin hyperpigmentation issues with Himanthalia elongata extract.

BACKGROUND: During aging, human skin is facing hyperpigmentation disorders: senile lentigo (chronobiologic aging) leads to loss of melanogenesis' control while solar lentigo (UV exposure) promotes an increase of oxidized proteins, melanogenesis, and lipofuscin. AIMS: Stromal-cell-derived-factor-1 (SDF-1) was identified as key regulator of hyperpigmentation and its expression is reduced in senescent fibroblasts, highlighting this protein as new target for skin hyperpigmentation. MATERIALS: We developed two skin explant models mimicking of senile and solar lentigo, based on H2 O2 systemic treatment and UV irradiation, respectively. We evaluated Himanthalia elongata extract (HEX) on these models after 5 days of treatment and analyzed SDF-1 expression and skin pigmentation. For solar lentigo, we also analyzed oxidized proteins and lipofuscin accumulation. Finally, we evaluated HEX in vivo on nearly 100 multi ethnicities' volunteers. RESULTS: SDF-1 expression decreased in senile lentigo model, associated with hyperpigmentation. HEX application restored SDF-1 expression, leading to skin pigmentation decrease. For solar lentigo, we showed an impact of UVs on SDF-1 expression linked to hyperpigmentation, while the application of HEX restored SDF-1 expression and reduced skin pigmentation. On same model, HEX reduced oxidized proteins quantity and lipofuscin which increased after UV exposure. Clinically, HEX reduced dark spot pigmentation on Caucasian volunteers' hands and on Asian and African volunteers' face after 28 days. DISCUSSION: We have developed ex vivo models mimetic of senile and solar lentigo and showed for a very first time that SDF-1 can be also a key regulator for UV-induced hyperpigmentation. CONCLUSION: Our ex vivo and clinical studies highlighted the power of HEX with strong reduction of dark spots regardless of volunteers' ethnicities.

Action of Mangifera indica Leaf Extract on Acne-Prone Skin through Sebum Harmonization and Targeting C. acnes.

(1) Background: Preclinical studies report that the ethanolic fraction from Mangifera indica leaves is a potential anti-acne agent. Nevertheless, the biological activity of Mangifera indica leaves has scarcely been investigated, and additional data are needed, especially in a clinical setting, for establishing the actual effectiveness of Mangifera indica extract as an active component of anti-acne therapy. (2) Methods: The evaluation of the biological activity of Mangifera indica extract was carried out through different experimental phases, which comprised in silico, in vitro, ex vivo and clinical evaluations. (3) Results: In silico and in vitro studies allowed us to identify the phytomarkers carrying the activity of seboregulation and acne management. Results showed that Mangifera indica extract reduced lipid production by 40% in sebocytes, and an improvement of the sebum quality was reported after the treatment in analyses performed on sebaceous glands from skin explants. The evaluation of the sebum quantity and quality using triglyceride/free fatty acid analysis conducted on Caucasian volunteers evidenced a strong improvement and a reduction of porphyrins expression. The C. acnes lipase activity from a severe acne phylotype was evaluated in the presence of Mangifera indica, and a reduction by 29% was reported. In addition, the analysis of the skin microbiota documented that Mangifera indica protected the microbiota equilibrium while the placebo induced dysbiosis. (4) Conclusions: Our results showed that Mangifera indica is microbiota friendly and efficient against lipase activity of C. acnes and supports a role for Mangifera indica in the therapeutic strategy for prevention and treatment of acne.

Bacterial taxa predictive of hyperpigmented skins.

Background and Aims: Dark spots, brown spots, or hyperpigmented spots (HPS) are oval or irregular brown areas of skin. Their emergence is associated with dysregulation of the immune system, and may also be caused by a deficiency in stromal cell-derived factor-1, leading to perturbed melanogenesis and accumulation of melanosomes within neighboring keratinocytes. The skin microbiota (living microorganisms present on the surface of the skin) is known to play essential roles in maintaining skin homeostasis and in regulating the immune system. Here, we investigated whether the microbiota could play a role in the emergence of HPS. Methods: The clinical study involved 38 European women, selected from among 74 volunteers. Participants were divided into two groups depending on the spot areas measured on their faces. The study was designed to avoid conflicting factors: both groups presented similar skin pH, hydration, transepidermal water loss, and sebum levels. The two cohorts were also age-matched, with a mean of 29-years-old for both. Results: Alpha-diversity of the microbiota was similar for the two groups. On skins with more HPS, seven bacterial genera were identified in significantly higher proportions and included opportunistic pathogens and inflammatory bacteria. Six bacterial genera, including bacteria showing antioxidant and anti-UV properties, were identified in significantly higher proportions on less spotted skins. Cross-domain association networks revealed distinct co-occurrences of genera between the two groups, suggesting nonidentical community structures and exchanges, depending on the HPS status. Conclusion: Our results reveal specific microbiota composition and networks on skins based on HPS status. Changes could alter communication with the immune system, leading to the emergence of dark spots. As an essential part of the overall skin ecosystem, and through its interaction with the skin matrix, the skin microbiota and its maintenance could be considered a new target for skincare applications.

The anti-wrinkles properties of sodium acetylated hyaluronate.

BACKGROUND: Intrinsic aging promotes wrinkles formation by an imbalance between matrix synthesis/degradation in favor of degradation. This is accelerated by the exposome leading to overproduction of protease and fewer remodeling. OBJECTIVE: Protecting the integrity of extracellular matrix appears as the most efficient anti-aging solution. We developed a grafted HA specifically designed to get anti-aging property due to a specific molecular weight and acetylation degree. METHODS: A transcriptomic analysis was performed on fibroblasts, followed by a measurement of MMP secretion and subsequent effect on collagen degradation. MMP expression in skin explants concerned by chronobiological and extrinsic aging was analyzed by immunostaining. A clinical study was conducted on volunteers presenting wrinkles on face to evaluate flash reduction of wrinkles after 6 h of application by profilometry and anti-aging efficacy after 2 months by VISIA® CR2.3. RESULTS: Transcriptomic analysis evidenced an inhibition of MMP gene expression with acetylated HA, confirmed by an inhibition of MMPs release by fibroblasts, and a protection of type I collagen against degradation. We confirmed the reduction of MMPs in mature skin and in skin explants exposed to UV and urban dust. We demonstrated during clinical studies the flash reduction effect of acetylated HA on crow's feet wrinkles and a filling of nasogenian areas 6 h after application, and a wrinkles number reduction on nasogenian area up to 2 months of application. CONCLUSION: We developed a new grafted HA owing protective properties against ECM degradation induced by chronobiological and extrinsic aging, leading to a significant and efficient anti-wrinkles effect.

Mannose-6-phosphate complex and improvement in biomechanical properties of the skin.

BACKGROUND: The dermis is composed of a tangle of macromolecules that provides the skin its biomechanical properties. During chronological aging, fibroblasts lose their ability to synthesize collagen and an accumulation of matrix metalloproteinases leads to an increase in collagen degradation. As a result, there is a decline in the biomechanical properties of the skin. Skin aging is accelerated by external factors such as UV radiation and pollution, which induce accumulation of oxidants, and so of oxidized proteins in the skin. AIMS: Atomic force microscopy (AFM) has emerged as an alternative method for studying the biomechanical properties of skin cells and tissues. METHODS/RESULTS: Thus, we identified mannose-6-phosphate complex as a new powerful molecule capable of reversing the visible signs of aging by reorganizing the collagen network of the dermis and by improving the skin biomechanical properties. This effect was correlated with clinical studies that showed a marked antiaging effect through a reduction in the number of crow's feet and in the depth and size of neck wrinkles. CONCLUSION: Mannose-6-phosphate complex appeared to be able to protect proteins in the dermis scaffold against oxidation and degradation, allowing an improvement in the skin biomechanical properties.

Overall renewal of skin lipids with Vetiver extract for a complete anti-ageing strategy.

OBJECTIVE: Skin lipids are essential in every compartment of the skin where they play a key role in various biological functions. Interestingly, their role is central in the maintenance of hydration which is related to skin barrier function and in the skin structure through adipose tissue. It is well described today that skin lipids are affected by ageing giving skin sagging, wrinkles and dryness. Thereby, developing cosmetic actives able to reactivate skin lipids would be an efficient ant-ageing strategy. Due to the strong commitment of our scientists to innovate responsibly and create value, they designed a high value active ingredient named here as Vetiver extract, using a ground-breaking upcycling approach. We evidenced that this unique extract was able to reactivate globally the skin lipids production, bringing skin hydration and plumping effect for mature skin. METHOD: In order to demonstrate the global renewal of lipids, we evaluated the lipids synthesis on cutaneous cells that produce lipids such as keratinocytes, sebocytes and adipocytes then on Reconstructed Human Epidermis and skin explants. We evaluated the expression of proteins involved in ceramides transport and barrier cornification. We then evaluated hydration and sebaceous parameters on a panel of mature volunteers. RESULTS: We firstly demonstrated that Vetiver extract induced sebum production from human sebocytes cells lines but also improved its quality as observed by the production of specific antimicrobial lipids. Secondly, we demonstrated that Vetiver extract was able to restore skin barrier with the increase of skin lipids neosynthesis on Reconstructed Human Epidermis and skin explants. We also evidenced that Vetiver extract stimulated the lipids transport and epidermal cornification. Finally, Vetiver extract showed a significant effect on adipogenesis and maturation of adipocytes at in vitro and ex vivo models. We confirmed all these activities by showing that Vetiver extract improved sebum production and brought hydration through an increase of lipids content and their conformation. Vetiver extract induced an improvement of skin fatigue and a plumping effect by acting deeply on adipose tissue. CONCLUSION: In conclusion, we developed an active ingredient able to bring anti-ageing effect for mature skin by a global increase of skin lipids.

OBJECTIF: Les lipides de la peau sont essentiels dans chaque compartiment de la peau où ils jouent un rôle clé dans diverses fonctions biologiques. Il est intéressant de noter que leur rôle est central dans le maintien de l'hydratation, liée à la fonction de barrière cutanée, mais aussi dans la structure même de la peau, par le biais du tissu adipeux. Il est bien décrit aujourd'hui que les lipides de la peau sont affectés par le vieillissement, ce qui entraîne un relâchement de la peau, des rides et une sécheresse. Ainsi, le développement d'actifs cosmétiques capables de réactiver les lipides de la peau serait une stratégie efficace de lutte contre le vieillissement. En raison de l'engagement fort de nos scientifiques à innover de manière responsable et à créer de la valeur, ils ont conçus un ingrédient actif à forte valeur ajoutée, appelé ici extrait de Vétiver, en utilisant une approche révolutionnaire de « up-cycling ¼. Nous avons démontré que cet extrait unique était capable de réactiver globalement la production de lipides de la peau, apportant une hydratation de la peau et un effet repulpant pour les peaux matures. MÉTHODES: Afin de démontrer le renouvellement global des lipides, nous avons évalué la synthèse des lipides sur les cellules cutanées qui produisent des lipides tels que les kératinocytes, les sébocytes et les adipocytes, puis sur un modèle d'Epiderme Humain Reconstruit et les explants de peau. Nous avons évalué l'expression des protéines impliquées dans le transport des céramides et la kératinisation de la barrière cutanée. Nous avons ensuite évalué l'hydratation et les paramètres sébacés sur un panel de volontaires matures. RÉSULTATS: Nous avons tout d'abord démontré que l'extrait de Vétiver induit la production de sébum à partir de lignées cellulaires de sébocytes humains mais améliore également sa qualité comme l'indique la production de lipides antimicrobiens spécifiques. Ensuite, nous avons démontré que l'extrait de Vétiver était capable de restaurer la barrière cutanée grâce à l'augmentation de la néosynthèse lipidique sur un modèle d'Epiderme Humain Reconstruit et sur des explants de peau. Nous avons également démontré que l'extrait de Vétiver stimulait le transport des lipides et la kératinisation de l'épiderme. Enfin, l'extrait de Vétiver a montré un effet significatif sur l'adipogenèse et la maturation des adipocytes dans des modèles in vitro et ex vivo. Nous avons confirmé à l'échelle clinique toutes ces activités en montrant que l'extrait de Vétiver améliorait la production de sébum et apportait une hydratation grâce à une augmentation de la teneur en lipides ainsi qu'une modification de leur conformation. L'extrait de Vétiver a induit une amélioration de la fatigue cutanée et un effet repulpant en agissant en profondeur sur le tissu adipeux. CONCLUSION: En conclusion, nous avons développé un ingrédient actif capable d'apporter un effet anti-âge aux peaux matures par une augmentation globale des lipides de la peau.