Role of ingestible carotenoids in skin protection: A review of clinical evidence.

Carotenoids, a class of phytonutrients, have been well established to boost skin's innate resistance against ultraviolet (UV) B-induced erythema (sunburn). Many of the published clinical studies thus far have focused on the measurement of erythema as the primary clinical indicator of skin protection against UVB radiation. More recent studies have shown that carotenoid supplementation provides even more skin protection than previously shown as new clinical and molecular endpoints beyond UVB-induced erythema have been reported. These recent studies have demonstrated that carotenoids also provide photoprotection against UVA-induced pigmentation and inhibit molecular markers of oxidative stress such as intercellular adhesion molecule 1, heme oxygenase-1, and matrix metalloproteinases 1 and 9. This article provides a comprehensive review of the published clinical evidence on skin benefits of carotenoids in the last five decades and indicates new perspectives on the role of ingestible carotenoids in skin protection.

Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders.

Though there is limited research confirming the purported topical benefits of cannabinoids, it is certain that cutaneous biology is modulated by the human endocannabinoid system (ECS). Receptors from the ECS have been identified in the skin and systemic abuse of synthetic cannabinoids, and their analogs, have also been associated with the manifestation of dermatological disorders, indicating the effects of the ECS on cutaneous biology. In particular, cannabidiol (CBD), a non-psychoactive compound from the cannabis plant, has garnered significant attention in recent years for its anecdotal therapeutic potential for various pathologies, including skin and cosmetic disorders. Though a body of preclinical evidence suggests topical application of CBD may be efficacious for some skin disorders, such as eczema, psoriasis, pruritis, and inflammatory conditions, confirmed clinical efficacy and elucidation of underlying molecular mechanisms have yet to be fully identified. This article provides an update on the advances in CBD research to date and the potential areas of future exploration.

Orally administered mixed carotenoids protect human skin against ultraviolet A-induced skin pigmentation: A double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Photoprotection of human skin is determined as the capacity of sunscreens to prevent ultraviolet (UV) B radiation-induced erythema and UVA radiation-induced pigmentation. It is unequivocal that, in addition to sunscreens, oral supplementation with carotenoids can protect human skin against UVB radiation-induced erythema. It is not known if this is also the case for UVA radiation-induced pigmentation. OBJECTIVE: To clinically evaluate the photoprotective effects of daily supplementation with carotenoids against UVA radiation-induced pigmentation. METHODS: In this double-blind, placebo-controlled trial, 60 subjects (Fitzpatrick types II-IV) were randomized to receive Nutrilite™ Multi Carotene supplement or placebo for 12 weeks. UVB-induced minimal erythemal dose (MED), UVA-induced minimal persistent pigmentation dose (MPPD) and skin carotenoid levels were measured at baseline, 4, 8, and 12 weeks of intervention. Skin color was evaluated by expert clinical graders and by colorimetry. Carotenoid levels in the skin were measured by the Biozoom® device. RESULTS: In the intervention group, a significant increase in comparison with the placebo group was observed in (a) skin carotenoid levels, (b) UVB-induced MED, and (c) UVA-induced MPPD values obtained by colorimetry. CONCLUSION: Daily supplementation with carotenoids protects human skin against both UVB-induced erythema and UVA-induced pigmentation.

Cytidine decreases melanin content in a reconstituted three-dimensional human epidermal model.

The process of melanin biosynthesis and its distribution throughout the skin is regulated by complex processes involving several enzymes in melanocytes. Recently, Diwakar et al. demonstrated that cytidine-a sialyltransferase inhibitor, 6'-sialyllactose (6'-SL) and 3'-sialyllactose (3'-SL) inhibited melanogenesis and melanosome transfer process. In this study, we have furthered this research, considering cytidine as a commercially viable and safe option over 6'-SL and 3'-SL. The efficacy of 2% w/v cytidine was studied in MelanoDerm™ skin equivalents in comparison with the positive control 1% w/v kojic acid and the vehicle control. Both the positive control and cytidine demonstrated a significant reduction in melanin content relative to the vehicle control. These experiments conclude that cytidine can effectively reduce melanin content in a skin equivalence assay and suggests that cytidine may be a good candidate for a skin lightening agent for human skin.

Clinical evaluation of the lightening effect of cytidine on hyperpigmented skin.

BACKGROUND: Melanocytes, which reside in the basal layer of the epidermis, produce the pigment melanin in cytoplasmic organelles known as melanosomes. Melanosomes are transferred to keratinocytes which provide the color in our skin. Recently, Diwakar et  al reported the crucial roles of protein glycosylation in both melanogenesis and melanosome transfer to keratinocytes, and each was inhibited by the nucleotide cytidine. OBJECTIVE: The main objective of this study was to determine the clinical effects of topical application of cytidine to the hyperpigmented regions of the face in a group of human volunteers. METHODS: A randomized, vehicle-controlled study was conducted for 12 weeks on healthy Korean female subjects. Cytidine was formulated into the lotion at concentrations of 2%, 3%, and 4% (w/w) and compared to the vehicle control formulation. The clinical outcomes were evaluated by performing visual assessment grading, measuring melanin index, skin brightness, and skin color parameters. In vitro skin penetration studies were conducted using Franz cell chambers for the 2% cytidine test formulation. RESULTS: The test group showed significant improvements in the visual assessment scores, melanin index, skin brightness, and skin color compared to the control group. Although significant dose-dependent improvements were seen in the clinical study, the in vitro Franz cell studies indicated that the clinical efficacy and potency of cytidine might be further enhanced by formulating a better topical delivery system, which will be the goal of our future studies. CONCLUSIONS: This randomized, double-blind, 12-week clinical study successfully demonstrated the efficacy of cytidine on skin depigmentation in a dose-dependent manner.

Chrysanthemum Morifolium Extract And Ascorbic Acid-2-Glucoside (AA2G) Blend Inhibits UVA-Induced Delayed Cyclobutane Pyrimidine Dimer (CPD) Production In Melanocytes.

BACKGROUND: Solar ultraviolet radiation (UV) induces DNA damages in skin via direct absorption of UVB or indirectly by photosensitization mediated through UVA. Recent findings have revealed that UVA induces cyclobutane pyrimidine dimer (CPD) generation via chemiexcitation in melanocytes hours after the exposure. This UVA-induced delayed CPD (dark CPD) constitutes the majority of CPD in melanocytes. These findings indicate that sun light can damage the skin hours after the exposure, suggesting the need for skin care products post sun exposure. The main objective of this study was to investigate whether a blend of Chrysanthemum Morifolium flower extract (Chrys) and vitamin C derivative, Ascorbic Acid-2-Glucoside (AA2G), can provide protective effects against reactive oxygen species, melanin formation and UVA-induced dark CPD. METHODS: Intracellular ROS levels were measured in epidermal keratinocytes using DHR123 dye. Melanogenesis inhibition efficacy was determined using B16 cells. As for the dark CPD measurement, Melan-a cells were treated with or without actives for 6 days, then irradiated with UVA at various doses. Cells were exposed with anti-CPD mAb followed by secondary Ab. CPD levels were determined by measuring fluorescent intensity using a high content imaging analysis. RESULTS: Chrys, AA2G and their blend at various concentrations demonstrated ROS scavenging activity. Though Chrys alone did not show significant melanogenesis inhibition in B16 assay, the blend of Chrys with AA2G demonstrated additive effects in comparison with AA2G alone. The blend of AA2G and Chrys at various concentrations exhibited enhanced efficacy for inhibiting dark CPD compared to AA2G alone. CONCLUSION: The results from this study indicate that the use of natural antioxidant, Chrys in combination with AA2G, provides protection against UVA-induced delayed CPD formation by enhancing ROS scavenging activity and melanogenesis inhibition. These findings could potentially be applied for formulating post-sun exposure skin care products, possibly extending to evening-after care products.

Size and Charge Dependence of Ion Transport in Human Nail Plate.

The electrical properties of human nail plate are poorly characterized yet are a key determinate of the potential to treat nail diseases, such as onychomycosis, using iontophoresis. To address this deficiency, molar conductivities of 17 electrolytes comprising 12 ionic species were determined in hydrated human nail plate in vitro. Cation transport numbers across the nail for 11 of these electrolytes were determined by the electromotive force method. Effective ionic mobilities and diffusivities at infinite dilution for all ionic species were determined by regression analysis. The ratios of diffusivities in nail to those in solution were found to correlate inversely with the hydrodynamic radii of the ions according to a power law relationship having an exponent of -1.75 ± 0.27, a substantially steeper size dependence than observed for similar experiments in skin. Effective diffusivities of cations in nail were 3-fold higher than those of comparably sized anions. These results reflect the strong size and charge selectivity of the nail plate for ionic conduction and diffusion. The analysis implies that efficient transungual iontophoretic delivery of ionized drugs having radii upward of 5 Å (molecular weight, ca. ≥ 340 Da) will require chemical or mechanical alteration of the nail plate.

Diffusion of uncharged solutes through human nail plate.

Passive diffusion data for uncharged solutes in hydrated human nail plate are collected and compared to the predictions of two theories for diffusion of uncharged solutes in dense keratin matrices. Quantitative agreement between the experimental data and the theories examined is poor. Concerns with both the experiments and the theories are identified and discussed. It is evident from the analysis that magnitude of the experimental nail permeability data may be questioned, as may the extrapolation procedures used to estimate the properties of dense fiber arrays from more dilute systems. Despite these caveats, it can be inferred that the microstructure of the nail plate is more complex than that assumed in the described models. The influence of residual lipids is implicated. More rigorous experiments and theoretical analysis of mass transport in the nail plate system are warranted. Successful completion of these tasks could lead not only to better predictions of transungual drug delivery, but also to better models of skin permeability, if hydrated nail plate can indeed serve as a model for the corneocyte phase of (partially hydrated) stratum corneum.