Efficacy of topical antioxidants in the skin hyperpigmentation control: A clinical study by reflectance confocal microscopy.

BACKGROUND: Some in vitro studies have reported the potential of antioxidants for the reduction of melanogenesis. However, it is important to assess the clinical efficacy of these substances in reducing skin hyperpigmentation. Thus, the aim of this study was to evaluate the clinical efficacy of dermocosmetic formulations based on antioxidants using Reflectance confocal microscopy (RCM). METHODS: Thirty-two healthy females aged 39-55 years were enrolled and divided into four groups: Vehicle (V), V with ascorbyl tetraisopalmitate (ATIP), V with Spirulina sp., and V with hydroxytyrosol-titrated olive extract. Imaging analyses by high-resolution methods and RCM were performed in the malar region of the face before and after a 42-day period of application of the studied formulations. RESULTS: Reflectance confocal microscopy imaging analyses showed a significant reduction of number of hyperreflective pixels and basal layer brightness after 42 days of application of formulations containing the antioxidants compared to vehicle and baseline values, suggesting an improvement of the skin pigmentation pattern. CONCLUSION: Reflectance confocal microscopy permitted the identification of skin hyperpigmentation and the assessment of the clinical efficacy of dermocosmetic formulations based on antioxidants in a noninvasive way. All formulations containing antioxidants significantly reduced skin hyperpigmentation after the period of application.

Efficacy and safety of a 3-in-1 antiaging night facial serum containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate through clinical and histological analysis.

BACKGROUND: Changes induced by intrinsic and extrinsic photoaging result in signs of skin aging including altered pigmentation and wrinkles. A 3-in-1 night facial serum (NFS) was developed to treat skin aging by antioxidative and retinoid-like mechanisms. OBJECTIVE: To determine the clinical and histological effects of the 3-in-1 NFS on signs of skin aging, clinically and histologically. METHODS & MATERIALS: Twenty-four subjects applied serum nightly for 12 weeks, and 12 subjects continued an extension study to 24 weeks. Clinical assessment of skin quality was performed by dermatologists. Skin biopsy was performed at 12 weeks to assess histological changes. RESULTS: There was a global aesthetic improvement over the duration of the study: +1.21 points at 12 weeks; +1.25 at 24 weeks. Skin texture, pigmentation, erythema, skin tone, complexion, lines, and wrinkles all significantly improved (P < .05). There was also a significant reduction in photodamage, hyperpigmentation, and wrinkle scores, most notably horizontal forehead expression lines, and marionette lines (P < .05 for all). Dermal and epidermal thickness increased without reaching statistical significance. CONCLUSION: The 3-in-1 NFS had clinically and statistically significant effects on signs of skin aging after 12 weeks, which became more pronounced after 24 weeks.

Epidermal and Dermal Hallmarks of Photoaging are Prevented by Treatment with Night Serum Containing Melatonin, Bakuchiol, and Ascorbyl Tetraisopalmitate: In Vitro and Ex Vivo Studies.

INTRODUCTION: Photoaging is a complex process that is chiefly the result of oxidative stress caused by ultraviolet (UV)-generated reactive oxygen species. To counter this process, we developed a 3-in-1 night facial serum (3-in-1 NFS) containing a combination of direct and indirect antioxidants and polyphenols that is designed to attenuate UV-generated free radicals and stimulate dermal protein synthesis. In clinical trials 3-in-1 NFS improved the appearance of photoaged skin. In this study we sought to identify some of the main histologic changes responsible for this. METHODS: We performed an immunolabeling analysis of some of the salient epidermal and dermal proteins in 3-in-1 NFS-treated primary epidermal keratinocytes (HEKs) and dermal fibroblasts (HDFs) in vitro, and in UV-exposed skin explants ex vivo. Numbers of apoptotic sunburn cells following exposure of 3-in-1 NFS-treated skin explants to UV radiation were also determined. RESULTS: We demonstrate that 3-in-1 NFS increases levels of filaggrin and aquaporin 3 in HEKs, and levels of collagen I and collagen III in HDFs in vitro. Levels of precursor procollagen type I and tropoelastin were increased in ex vivo skin explants. Numbers of apoptotic sunburn cells were significantly reduced in UV-exposed skin explants. These effects were only observed with the combination of ingredients in 3-in-1 NFS, suggesting that they have a synergistic effect on photoaged skin biology. CONCLUSION: Our results show that some of the histological hallmarks of photoaging are improved with the use of 3-in-1 NFS.

Clinical evidence of the efficacy and safety of a new 3-in-1 anti-aging topical night serum-in-oil containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate: 103 females treated from 28 to 84 days.

BACKGROUND: Topical melatonin is a potent antioxidant, yet there have been few clinical studies on its anti-aging effects on the skin. OBJECTIVES: To clinically assess the anti-aging efficacy and safety of a new 3-in-1 night facial serum (NFS) combining melatonin with bakuchiol, a novel retinol-like ingredient, and ascorbyl tetraisopalmitate, in all skin types. METHODS: Five clinical studies were performed, with a total of 103 subjects treated from 28 to 84 days. Under dermatologist supervision, a 3-month efficacy and safety study evaluated anti-aging properties by clinical scoring and instrumental evaluations. Two studies evaluated skin hydration properties for 12 hours after a single application of NFS. Two studies were performed in oily skin: a 1-month efficacy and safety study and a 1-month comedogenesis study. RESULTS: After 12 weeks, clinical evaluation showed a statistically significant decrease in wrinkles (11%), an increase in skin firmness (8%), a reduction in redness (70%; P < 0.01 for all), and an overall improvement in skin quality and complexion. The reduction in wrinkles and the increase in skin firmness were also supported by instrumental evaluations (Dermatop and Dynaskin). Hydration levels increased significantly from 30 minutes until 12 hours and transepidermal water loss significantly decreased after 4H and 6H. Subjects favorably evaluated the efficacy and cosmetic properties of the serum, and it was well tolerated in all skin types including oily skin. CONCLUSIONS: This 3-in-1 NFS showed significant clinical anti-aging effects when applied once daily and was well tolerated.

Melatonin, bakuchiol and ascorbyl tetraisopalmitate synergize to modulate gene expression and restore Hypoxia-Inducible Factor 1 signaling in UV-exposed skin.

Chronic exposure to solar ultraviolet (UV) radiation induces changes to the expression of hundreds of genes in the skin and modulates cellular signaling pathways that alter its structure, function and appearance. To counter these effects, we have developed a 3-in-1 night facial serum (3-in-1 NFS) comprising melatonin, bakuchiol and ascorbyl tetraisopalmitate that is designed to attenuate UV-generated free radicals and support new collagen synthesis. In order to better define its mechanism of action and gain insight into how it might influence the biology of photoaged skin, we performed a transcriptomic analysis of ex vivo skin explants that had been exposed to UV light and treated with 3-in-1 NFS each day for 4 consecutive days. Differentially expressed mRNAs and microRNAs (miRNA) were identified by RNA sequencing and a miRNA interactome was developed. Pathway enrichment analysis was performed to identify pathways likely modulated by 3-in-1 NFS. Our analysis revealed that the combination of active ingredients in 3-in-1 NFS exerted a synergistic effect on skin biology and modulated the expression of genes implicated in the regulation of collagen biosynthesis, angiogenesis, skin barrier function and cellular metabolism. Pathway analysis indicated that these events are driven by Hypoxia-Inducible Factor 1α (HIF-1α) whose expression in UV-exposed skin was partially restored upon 3-in-1 NFS treatment. To our knowledge, 3-in-1 NFS is the first non-drug demonstrated to act upon this pathway in the skin.

Assessment of penetration of Ascorbyl Tetraisopalmitate into biological membranes by molecular dynamics.

The present work, involves the simulation of the transport of a vitamin C derivative, Ascorbyl Tetraisopalmitate (ATI), through human skin by molecular dynamics. Percutaneous absorption of the ATI molecule through the infundibulum, an important route of absorption into the hair follicle of the human skin, has been modeled and compared with the stratum corneum membrane. The comparative study was done using molecular dynamics with Martini force field. In infundibulum, a single ATI molecule require more time to penetrate, and the data obtained suggested that a high concentration of ATI molecule accelerated the process of penetration. In conclusion, the ATI molecule was found to have more affinity towards the stratum corneum as compared with the infundibulum, and it followed a straight pathway to penetrate (until 600ns of simulation). In the infundibulum, it showed less affinity, more mobility and followed a lateral pathway. Thus, this work contributes to a better understanding of the different molecular interactions during percutaneous absorption of active molecules in these two different types of biological membranes.

Stability evaluation of tocopheryl acetate and ascorbyl tetraisopalmitate in isolation and incorporated in cosmetic formulations using thermal analysis / Estabilidade de avaliação de acetato de tocoferol e ascorbil tetraisopalmitato isoladamente e incorporados em formulações de cosméticos por meio de análise térmica

In view of the increase in the number of cosmetic preparations containing antioxidant vitamins, chiefly, due to their action in preventing the process of skin aging, there is a need to develop pre-formulation studies and to validate analytical methods in order to obtain high quality products. Thus, the objective of this research was to evaluate and compare the thermal behavior of tocopheryl acetate and ascorbyl tetraisopalmitate as raw materials, and incorporated into a base cream. Thermogravimetry (TG / DTG) and differential scanning calorimetry (DSC) were used for this purpose. Both vitamins were found to be stable up to 250ºC. The base cream (placebo) and the sample (base cream containing the vitamins) presented different weight loss. Thermal analysis has shown itself to be an excellent tool for the characterization of these vitamins and can be used in routine analysis for quality control of this type of cosmetic formulation.

Considerando o potencial antioxidante das vitaminas utilizadas em produtos cosméticos, seu uso na prevenção do processo de envelhecimento da pele e a necessidade de estudos de pré-formulação que garantam o desenvolvimento de cosméticos de qualidade, foi objetivo deste trabalho avaliar e comparar o comportamento térmico dos ativos acetato de tocoferila e tetraisopalmitato de ascorbila, matérias-primas, isoladamente e incorporados em creme base. As técnicas termogravimetria/termogravimetria derivada (TG/DTG) e calorimetria exploratória diferencial (DSC) foram utilizadas para tal finalidade. Verificou-se que as vitaminas mantiveram-se estáveis até a temperatura de, aproximadamente, 250 ºC, observando-se diferença na perda de massa entre o creme base e o creme base associado às vitaminas. Assim sendo, a análise térmica mostrou-se como excelente ferramenta para caracterização das vitaminas e do creme base, podendo ser empregada em análises de rotina no controle de qualidade deste tipo de formulação cosmética.