Natural Retinol Analogs Potentiate the Effects of Retinal on Aged and Photodamaged Skin: Results from In Vitro to Clinical Studies.

INTRODUCTION: Plants are a source of natural ingredients with retinol-like properties that can deliver anti-aging benefits without the side effects typically associated with retinoid use. We hypothesized that by combining two such analogs, bakuchiol (BAK) and Vigna aconitifolia extract (VAE), with the potent retinoid retinal (RAL), the anti-photoaging potential of RAL could be enhanced without compromising its skin irritation profile. The purpose of this study was to demonstrate that BAK and VAE potentiate the anti-photoaging activity of RAL. METHODS: Gene expression profiling of full-thickness reconstructed skin was first used to examine the impact of BAK or VAE in combination with RAL on skin biology. Next, the irritative potential of this combination, and its capacity to reverse key signs of photoaging in an ex vivo model was assessed. Finally, a proof-of-concept open label clinical study was performed to evaluate the anti-photoaging capacity and skin compatibility of a cosmetic formulation (tri-retinoid complex; 3RC) containing this complex in combination with other well characterized anti-photoaging ingredients. RESULTS: In vitro profiling suggested that combining 0.1% RAL with BAK or VAE potentiates the effect of RAL on keratinocyte differentiation and skin barrier function without affecting its skin irritation profile. When formulated with other anti-photoaging ingredients, such as niacinamide and melatonin, 3RC reversed ultraviolet radiation-induced deficits in structural components of the dermal extracellular matrix, including hyaluronic acid and collagen. In vivo, it led to a reversal of clinical signs of age and photodamage, with statistically significant improvement to skin firmness (+5.6%), skin elasticity (+13.9%), wrinkle count (-43.2%), and skin tone homogeneity (+7.0%), observed within 28 days of once nightly use. Notably, the number of crow's feet wrinkles was reduced in 100% of subjects. Furthermore, 3RC was very well tolerated. CONCLUSION: These data suggest that 3RC is a highly effective and well-tolerated treatment for photoaging.

Outdoor clinical testing with reference sunscreens to determine differences in skin response between populations of different ethnicity: A combined data analysis from 128 subjects.

BACKGROUND: Two previously published clinical studies by our group assessed erythema and pigmentation responses in outdoor conditions with three reference sunscreens, comparing their effectiveness under the full spectrum of natural sunlight. These studies followed an almost identical protocol but were conducted in two different locations and in two ethnic groups: broadly, Chinese (Singapore) and White European (Mauritius). We analysed the data from these two study populations to compare differences in skin response according to ethnicity. METHODS: The analysis included 128 subjects (53 were Chinese from Singapore and 75 were White European from Mauritius and Singapore). Products used were the reference sunscreens P3 (sun protection factor [SPF] 15), P5 (SPF 30) and P8 (SPF 50+) from ISO norm 24444:2019. Participants were exposed to outdoor sunlight for 2-3 h, depending on baseline ITA. Endpoints were erythema at 24 h: clinical score and colorimetry (Δa*) and pigmentation at 1 week based on colorimetry (ΔL* and ΔITA). RESULTS: Among those with baseline ITA > 41, there were differences in erythemal response between the Chinese and White European groups, the White European group being more erythematous and also having a higher rate of photoprotection failure particularly at SPFs 15 and 30. CONCLUSION: Differences in skin response to sun influenced by ethnicity should be taken into account when making recommendations on sun safety.

Photoprotection for people with skin of colour: needs and strategies.

Skin of colour or pigmented skin has unique characteristics: it has a higher eumelanin-to-pheomelanin ratio, more mature melanosomes, an increased amount of melanin distributed in the upper layers of the epidermis, and more efficient DNA repair compared with lighter skin. However, individuals with skin of colour are at a significant risk of skin damage caused by ultraviolet radiation, including the development of photodermatoses and photoageing changes such as uneven skin tone, and are predisposed to pigmentary disorders. In fact, one of the most common conditions leading to dermatology consultations by patients with skin of colour is photoexacerbated pigmentary disorders. Unfortunately, individuals with skin of colour may be less prone to engage in photoprotective measures, including the use of sunscreens. Physicians are also less likely to prescribe sunscreens for them. There is thus a clear need for better education on photodamage and for more efficient and suitable photoprotection in populations with skin of colour. However, this need has thus far only partially been met, and the development of sunscreen products designed to provide optimal photoprotection for people with skin of colour remains a challenge. Targeted sunscreens for individuals with skin of colour require optimal cosmetic appeal (leaving no white residue and not disrupting skin tone). They should include broad-spectrum [ultraviolet (UV)B/UVA] protection with high sun protection factor, as well as protection against long-wave UVA (UVA1) and visible light, as these wavelengths are capable of inducing or augmenting pigmentary disorders. They may also contain depigmenting agents for patients with pigmentary disorders.

Prevention of Polymorphic Light Eruption Afforded by a Very High Broad-Spectrum Protection Sunscreen Containing Ectoin.

INTRODUCTION: Polymorphic light eruption (PLE) is the most common idiopathic, acquired photodermatosis. The pathophysiology of PLE is not yet fully understood but seems to involve immunological mechanisms, UVA-induced oxidative stress, and the subsequent elicitation of a cellular stress response affecting keratinocyte gene expression and skin immune function. In the present study, a high broad-spectrum sunscreen medical device (MD), containing a very high protection complex of UVB and UVA filters and ectoin, was investigated for its ability to protect against UVA-induced PLE. METHODS: The study was carried out as a monocentric, double-blinded, randomized, untreated controlled design. The test MD was applied (2 mg/cm2) on one side of the chest according to a randomization list of 15 patients with a typical history of PLE, and the contralateral area remained untreated. After product application, the test areas were exposed daily to increasing doses of UVA radiation (from 40 to 60 J/cm2) until a PLE reaction was detected or for a maximum of five consecutive days. Evaluations of induced PLE included clinical scoring and chromametry for erythema and pigmentation. RESULTS: Overall, no positive PLE reaction was observed on the side of the chest treated by the test MD, whereas positive PLE reactions were triggered on the untreated side of 13 subjects. Subjective sensations were very rare on the MD-treated side but were numerous and more severe on the untreated side. Chromametry and clinical visual inspection indicated that the skin color was unchanged on the MD-protected side, whereas high increased values of erythema and pigmentation were observed on the untreated chest side. CONCLUSION: This MD sunscreen based on a complex of UVA-UVB filters and 1% of ectoin may be effective in preventing UVA-induced PLE. New studies comparing this MD sunscreen versus the same product without ectoin should be conducted. CLINICALTRIALS: gov identifier: NCT05320315 (retrospectively registered 09/17/2021).

Melasma: The need for tailored photoprotection to improve clinical outcomes.

BACKGROUND/PURPOSE: Melasma is a frequent photoexacerbated hyperpigmentary disorder, which can significantly impact on the quality of life. We sought to review the pathogenesis of melasma, and the role of photoprotection in the prevention and treatment of this disorder. METHODS: We conducted a narrative review of the literature. We performed literature searches with PubMed from January 1990 to December 2021 using the keywords "melasma," "pathogenesis," "ultraviolet radiation," "visible light," "photoprotection," and "sunscreens." RESULTS: The physiopathology of melasma includes a complex interaction between genetics, sex hormones, and sun exposure. Visible light, in particular high-energy visible light (HEVL), and long-wave UVA (UVA1) play a key role in melasma pathophysiology, and recent research suggests that melasma shares many features with photoaging disorders. Melasma disproportionately affects dark-skinned individuals. Some 30% to 50% of South Americans and Asians, among other ethnicities, can present with melasma. Dark-skinned patients take fewer photoprotective measures. Also, the majority of melasma patients do not adequately follow photoprotection recommendations, including the application of sunscreen. Intensive use of a broad-spectrum sunscreen can prevent melasma in high-risk individuals, can lessen melasma severity (associated or not with depigmenting agents), and can reduce relapses. CONCLUSIONS: Due to the physiopathology of melasma, sunscreens should be broad-spectrum with high sun protection factor, and provide high protection against UVA1 and VL. Sunscreens should be cosmetically acceptable and leave no white residue. Tinted sunscreens are an excellent choice, as pigments can protect from HEVL and UVA1, and may provide camouflage, but they must offer colors that match the skin tone of each patient.

Exposome and Skin: Part 1. Bibliometric Analysis and Review of the Impact of Exposome Approaches on Dermatology.

INTRODUCTION: Most skin disorders, such as atopic dermatitis, psoriasis, skin cancer or age-related skin issues, are the result of a complex interaction between genetic and environmental factors over time. As an external organ, the skin provides the opportunity to study the link between exposure to the environment and several specific biological responses using an exposome approach. The aim of this review was to identify the state of the art of exposome approaches and elucidate the impact of the new era of exposomics on dermatology. METHODS: Two parallel and independent bibliometric analyses were conducted based on documents extracted from the Core Collection and the Science Citation Index Expanded (SCI-Expanded) databases from the Clarivate Analytics' Web of Science (WOS) platform by using the following search terms "exposome" and "skin exposome". In both searches, we used the topic field that includes title, abstract, author keywords and keywords plus terms and the following filters: "English language" and all documents published up to 30 September 2021. We further analysed and interpreted documents extracted in plain text format. RESULTS: Based on the defined searches, 910 documents were identified as being related to "exposome" and 45 as being related to "skin exposome". Environmental sciences and toxicology were the most impacted research areas, and aging, cancer and respiratory allergies were the most documented diseases while, surprisingly, dermatology was much less impacted. Krutmann et al. were the pioneers in implementing this new concept in dermatology with publication of "The skin aging exposome" in 2017 (J Dermatol Sci. 2017;85:152-61). After this tipping point, the number of publications in dermatology evaluating the impact of exposome factors in many skin disorders has steadily increased. CONCLUSIONS: Exposome studies are rapidly attracting interest in dermatology. The results of these studies will undoubtedly improve our understanding of why and under which circumstances some individuals develop skin disorders and help design tailored prevention strategies for patients suffering from these disorders.

Exposome and Skin. Part 2. The Influential Role of the Exposome, Beyond UVR, in Actinic Keratosis, Bowen's Disease and Squamous Cell Carcinoma: A Proposal.

Actinic keratosis (AK) is the main risk factor for the development of cutaneous invasive squamous cell carcinoma (SCC). It represents the first sign of severe chronic ultraviolet radiation exposure, which has a clear significant effect. Nevertheless, the skin is exposed to many other exposome factors which should be thoroughly considered. Our aim was to assess the impact of exposome factors other than ultraviolet radiation (UVR) on the etiopathology of AK and Bowen's disease (BD) and progression of AK to SCC and to design tailored prevention strategies. We performed an exhaustive literature search in September 2021 through PubMed on the impact of exposome factors other than UVR on AK, BD and SCC. We conducted several parallel searches combining terms of the following topics: AK, BD, SCC and microbiome, hormones, nutrition, alcohol, tobacco, viral infections, chemical contaminants and air pollution. Notably, skin microbiome studies have shown how Staphylococcus aureus infections are associated with AK and AK-to-SCC progression by the production of chronic inflammation. Nutritional studies have demonstrated how a caloric restriction in fat intake, oral nicotinamide and moderate consumption of wine significantly reduce the number of premalignant keratoses and SCC. Regarding lifestyle factors, both alcohol and smoking are associated with the development of SCC in a dose-dependent manner. Relevant environmental factors are viral infections and chemical contaminants. Human papillomavirus infections induce deregulation of cellular proliferation and are associated with AK, BD and SCC. In addition to outdoor jobs, occupations such as industrial processing and farming also increase the risk of developing keratoses and SCC. The exposome of AK will undoubtedly help the understanding of its etiopathology and possible progression to SCC and will serve as a basis to design tailored prevention strategies.

Photoprotection in Outdoor Sports: A Review of the Literature and Recommendations to Reduce Risk Among Athletes.

Solar exposure, for long hours and often at peak times with limited shade available, predisposes athletes to episodic sunburn and chronic damage, causing increased risk of precancerous lesions and skin cancer. Environmental factors and training intensity affect risk. Clothing provides good protection, but changing established "uniforms" may not be possible for reasons of practicality, safety, or simply custom. Although physical activity should be encouraged for its physical and mental benefits, risk of skin damage should be minimised. We review existing behaviours, skin cancer risk, and campaigns in the sporting population and highlight key recommendations to help sun protection practices become engrained in sports practice.

Outdoor sunscreen testing with high-intensity solar exposure in a Chinese and Caucasian population.

BACKGROUND: Currently, sunscreens' sun protection factor (SPF) and ultraviolet (UV) A protection are tested separately under indoor conditions, without considering external conditions that may affect performance. Studies are often conducted in Caucasian individuals; other racial groups may respond differently. METHODS: An outdoor, double-blind, intra-individual study was performed in 63 healthy Chinese and Caucasian volunteers in Singapore. Subjects underwent one outdoor sun exposure lasting 2-3 hours. ISO reference products P3 (SPF 15), P5 (SPF 30), and P8 (SPF 50+) applied at 2 mg/cm2 were compared against each other and against an untreated exposed area (positive control) and an unexposed area (negative control). Endpoints were investigator global assessment (IGA) of erythema at 24 hours, IGA of pigmentation at 1 week, and colorimetry (a*, L*, and ITA) at 24 hours and 1 week. RESULTS: Clinical erythema and pigmentation scores were statistically significantly different among the three sunscreens, with the highest SPF product providing the highest protection, confirming the discriminatory capacity of the model used. Colorimetric assessment correlated well with clinical evaluation. CONCLUSION: This study confirmed the feasibility of ranking sunscreens (at 2 mg/cm2 ) based on clinical effects of high-intensity outdoor solar radiation. Larger studies are needed to look at differences in erythema and pigmentation reactions between Chinese and Caucasian individuals, which could be relevant for photoprotection.

Photoprotection of the Skin from Visible Light‒Induced Pigmentation: Current Testing Methods and Proposed Harmonization.

Visible light (VL) can induce pigmentary alterations, especially in dark-skinned individuals, and exacerbate photodermatoses and pigmentary disorders. Currently, there is no standardized method for assessing sunscreen protection against VL. On the basis of a critical review of published in vitro and in vivo methods, a VL photoprotection assessment method based on pigmentation is proposed.

The Role of Photoprotection in Optimizing the Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with an estimated prevalence of 10-15% in children and 2-10% in adults. Clinically, there is notable phenotypic variability driven by a complex interaction between genetics, immune function, and the environment. Impairment of the skin barrier plays a significant role in the pathogenesis of AD. The apparent beneficial effect of sunlight in patients with atopic eczema is questioned due to its capacity to disrupt the skin barrier and generate free radicals that can damage proteins, lipids, and DNA. The sum of the external factors that an individual is exposed to throughout their lifetime is termed the exposome. Environmental factors such as sun exposure, temperature, and humidity contribute to both AD flares and regional prevalence variation. Literature on photoprotection in atopic dermatitis is very scarce. The use of adequate sunscreens in atopic dermatitis can ensure the level of photoprotection required to prevent skin photoaging and skin cancer and to mitigate skin barrier dysfunction, decrease inflammation, and neutralize facial redness. Herein we discuss and review the role of UV radiation and the exposome in the etiology of AD, as well as the role of adequate photoprotection.

Impact of ultraviolet radiation and exposome on rosacea: Key role of photoprotection in optimizing treatment.

BACKGROUND: Pathophysiology of rosacea is not completely understood and involves a complex interaction among genetics, ultraviolet (UV) light, microorganisms, impaired skin barrier, neuronal and vascular dysfunction, and immune system disruption. AIMS: To describe the etiology of rosacea with an emphasis on the role of UV radiation and exposome, and to review the importance of non-pharmacologic strategies focusing on photoprotection. METHODS: We conducted a narrative review of the literature. We performed literature searches with PubMed from January 1990 to November 2020 using the keywords "rosacea", "pathogenesis", "ultraviolet radiation", "exposome", "photoprotection", "sunscreens" and "non-pharmacologic agents". The search was limited to English, Spanish, and French language articles. RESULTS: Several environmental factors such as UV light, diverse microorganisms, air pollution, tobacco smoking, nutrition, and psychological stress showed to trigger or worsen rosacea. UV radiation was reported to induce pro-inflammatory, pro-angiogenic, and pro-fibrotic responses. We found 6 original articles about the impact of sunscreens on rosacea. The use of sunscreens containing ingredients with emollient, anti-inflammatory, and/or vasoregulatory properties was shown to significantly improve symptomatology. CONCLUSION: UV radiation and the exposome play a key role in the development of rosacea. UV light is implicated in all significant aspects of rosacea: skin inflammation, neoangiogenesis, telangiectasia, and fibrosis, and may even initiate rosacea. While the use of sunscreens is widely recommended, the literature on the impact of photoprotection in rosacea is scarce. Adequately formulated sunscreens could not only provide the required level of photoprotection, but may also help to mitigate the barrier dysfunction, neutralize facial redness (tinted sunscreens), and decrease inflammation and vascular dysfunction.

Glycolic acid adjusted to pH 4 stimulates collagen production and epidermal renewal without affecting levels of proinflammatory TNF-alpha in human skin explants.

BACKGROUND: Glycolic acid (GA) is an effective way of reversing the signs of age and photodamage. GA enhances desquamation of the stratum corneum and induces biological responses that can help restore skin's integrity. GA can, however, cause irritation, especially when its concentration is high, and its pH is low. Thus, most commercially available products for home use contain relatively low GA concentrations and are partially neutralized to a pH around 4. AIMS: The aim of this study was to determine the biological effects and relative efficacy of cosmetic formulations containing GA at concentrations ranging from 8% to 25% at pH 4 in human ex vivo skin explants. METHODS: Human skin explants were topically treated with gel formulations and oil-in-water creams containing 8%, 10%, 15%, or 25% GA, adjusted to pH 4, daily for 5 days. The degree of desquamation, their effect on cell proliferation, and their impact upon total collagen levels were determined 24 hours later. Levels of tumor necrosis factor-alpha (TNF-α) were measured after days 3 and 6. RESULTS: All formulations effectively induced desquamation in a concentration-dependent manner. Total collagen levels were increased at all concentrations, with greatest effects at higher GA concentrations. No effect on TNF-α expression was observed. CONCLUSIONS: These data suggest that partially neutralized GA formulations retain skin rejuvenating properties without causing irritation and inflammation and that their use can be tailored to individual needs based on the concentration of GA in the formulation.

Night Cream Containing Melatonin, Carnosine and Helichrysum italicum Extract Helps Reduce Skin Reactivity and Signs of Photodamage: Ex Vivo and Clinical Studies.

INTRODUCTION: Extrinsic factors, such as solar radiation and urban pollution, cause damage that alters the structure, function and appearance of skin. The aim of this study was to determine the ability of a night cream containing melatonin, carnosine and Helichrysum italicum extract (referred to here as Night Cream) to reduce extrinsic skin damage, and to evaluate the efficacy of this Night Cream to reduce clinical signs of age and photodamage under normal conditions of use. METHODS: Recovery from extrinsic damage was assessed by exposing human skin explants to ultraviolet (UV) A, infrared light, blue light or pollution and then treating the stress-exposed explants with Night Cream. Markers of oxidative stress were examined by immunohistochemistry. Anti-aging and calming properties were determined in four single-center, open-label trials involving 117 individuals. Subjects applied Night Cream to their face once nightly for up to 12 weeks. Improvements in clinical signs of age and photodamage, and reduction of lactic acid-induced stinging were evaluated by investigator assessment and subject self-assessment. RESULTS: Night Cream significantly reduced oxidative stress in human skin ex vivo. Clinically, hydration (+ 64.4%; p < 0.05) and transepidermal water loss (TEWL) values (- 10.0%; p < 0.05) were improved within 1 h of use. Wrinkle counts were reduced by up to 18.9% (p < 0.05), and brown and UV spot numbers by 5.5% (p < 0.05) and 13.2% (p < 0.05), respectively. Lactic acid-induced stinging was significantly reduced within 7 days of use, with 86.7% of subjects reporting that their skin felt calmer. CONCLUSION: These findings suggest that Night Cream reduces skin damage caused by environmental factors and that its nightly use can improve clinical signs of aging with additional skin calming benefits.

Management Pearls on the Treatment of Actinic Keratoses and Field Cancerization.

Field cancerization (FC) is a chronic disease involving multiple clinical and subclinical actinic keratoses (AK) on large photo-exposed surfaces with multifocal areas of dysplasia and precancerous changes. Patients and treatment must be properly monitored and managed to avoid aggravation and progression of the disease. Management of actinic keratoses includes lesion-directed treatments, such as cryotherapy and field-directed therapies. Field-directed therapies may have the potential to address subclinical damage, reduce AK recurrence rates and potentially reduce the risk of squamous cell carcinoma development. Multiple studies have demonstrated the efficacy of field-directed treatments, including 5-fluorouracil, photodynamic therapy, imiquimod, chemical exfoliation with trichloroacetic acid and diclofenac gel, for multiple AK and FC. The choice of therapy should be based on multiple factors, such as efficacy, tolerability, patient risk profile, costs and cosmetic results. Management of AK includes not only treatment but also prevention. Medical devices, such as sunscreens containing liposome-encapsulated DNA repair enzymes, can repair DNA damage associated with chronic UV radiation and reduce the number of new AK lesions. Here we provide therapeutic pearls and expert opinions on the treatment of AK and FC (as monotherapy or in combination) with the overall aim to achieve better, faster, and well-tolerated clinical responses.

A Treatment Combination of Peels, Oral Antioxidants, and Topical Therapy for Refractory Melasma: A Report of 4 Cases.

BACKGROUND: Melasma is a difficult-to-treat, recurrent pigmentary disease. Combined therapy gives better, longer-lasting results. OBJECTIVE: To determine the clinical effects of a treatment protocol of trichloroacetic acid, phytic acid and ascorbic acid peel combined with oral antioxidant supplement and topical treatment for refractory melasma. PATIENTS AND METHODS: We present four cases of patients with melasma, who, despite multiple treatments including hydroquinone, showed no improvement. We initiated a 16-week protocol involving 3 in-clinic peels (4 weeks apart) and a daily home treatment. The peels contained 30% trichloroacetic acid, 2% phytic acid, 8% L-ascorbic acid, Camellia sinensis leaf extract and Vitis vinifera seed extract. The home treatment was a depigmenting serum (4-butyl resorcinol, hydroxy-phenoxy propionic acid and niacinamide), a specific SPF50+ sunscreen, and an oral supplement (Polypodium leucotomos; green tea extract; Vitis vinifera; vitamins C, E, and D; and carotenoids), all in the morning, and, at night, a compounded gel-cream (4% hydroquinone, 0.025% tretinoin and 1% hydrocortisone). After 16 weeks, the gel-cream was stopped; the rest of the regimen (topical and oral) was continued for 12 further weeks. Melasma was assessed using the melasma severity scale (MSS) before starting the protocol, and at 4 and 12 weeks after the last peel. Photographs were taken before treatment and at the last evaluation. Patients indicated their satisfaction on a 5-point scale. RESULTS: All patients had good tolerance to the procedures. Three showed an excellent (>75%) improvement and one showed a good (50-75%) improvement. All four were very satisfied. At follow-up (12 weeks after last peel), no patients had recurrence. CONCLUSION: This protocol of trichloroacetic acid, phytic acid and ascorbic acid peel combined with an oral supplement and topical daily treatment is a viable treatment option for refractory melasma.

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.

Prospective Evaluation of the Efficacy of a Food Supplement in Increasing Photoprotection and Improving Selective Markers Related to Skin Photo-Ageing.

INTRODUCTION: Skin exposure to ultraviolet radiation (UVR) can cause oxidative stress, particularly in the absence of adequate protective measures or in individuals with a sensitive skin type. Most commonly, protection from UVR entails the use of topical sunscreens. Sunscreens, however, have various limitations. The objective of this study was to evaluate the efficacy and tolerability of an oral food supplement containing a combination of actives with mainly antioxidative properties (vitamins A, C, D3, E, selenium, lycopene, lutein, as well as green tea, polypodium and grape extracts) in the context of photoprotection. METHODS: Photoprotective efficacy was assessed in a 12-week-long, open, prospective and monocentric clinical study with 30 subjects (27 women and 3 men) having a Fitzpatrick skin type I-III and manifesting clinical ageing signs. The study included several visits (14, 28, 56, and 84 days after starting supplement intake), in which photoprotection was evaluated by the measurement of the minimal erythema dose (MED), while the antioxidant capacity of the skin was assessed through ferric reducing antioxidant power (FRAP) and malondialdehyde (MDA) assays. Additionally, several skin parameters (including radiance, elasticity, and moisture) were evaluated. Product evaluation was performed throughout the length of the study by means of a self-assessment questionnaire, and safety was monitored through a self-recording of all observed adverse reactions. RESULTS: The MED levels increased significantly compared to baseline throughout the study visits, reaching an increase of + 8.1% at T84, p < 0.001. FRAP results also indicated a significant increase in the antioxidant capacity of the skin compared to baseline (+ 22.7% at T84, p < 0.001), while the MDA assay showed a significant decrease in MDA concentration compared to baseline (- 6.4% at T84, p < 0.001) which, in line with the FRAP results, indicated enhanced antioxidative protection of the skin. All assessed skin parameters, including radiance (+ 36.1% at T84, p < 0.001), gross elasticity (+ 13.2% at T84, p < 0.001), net elasticity (+ 28.0% at T84, p < 0.001), and moisture (+ 13.8% at T84, p < 0.001) were also significantly improved. The product was well tolerated as no adverse events were attributed by the investigators to the use of the product. Additionally, the global score obtained from the self-assessment questionnaires provided overwhelmingly positive feedback from the study subjects. CONCLUSIONS: The food supplement evaluated in this study was effective and well-tolerated by the subjects, demonstrating a beneficial effect in terms of photoprotection, enhancing the antioxidative status of the skin and improving general skin condition. TRIAL REGISTRATION: Retrospectively registered 3rd October 2019, ISRCTN18121679.