Rhododendrol (4-(4-hydroxyphenyl)-2-butanol) has been used as a lightening/whitening cosmetic but was recently reported to induce leukoderma. Although rhododendrol has been shown to be transformed by tyrosinase to hydroxyl-rhododendrol, which is cytotoxic to melanocytes, its detailed mechanism of action including the involvement of reactive oxygen species is not clearly understood. To confirm the relationship of hydroxyl radical generation to melanocyte cytotoxicity induced by rhododendrol, this study was performed. An electron spin resonance method with a highly sensitive detection system was utilized to monitor hydroxyl radicals generated from two distinct normal human epidermal melanocyte lines with different levels of tyrosinase activity after the addition of various amounts of rhododendrol. Cytotoxicity of rhododendrol was analyzed by AlamarBlue assay under the same condition. Hydroxyl radicals were generated depending on the amounts of rhododendrol and/or tyrosinase. After the correlation between hydroxyl radical generation with melanocyte viability was confirmed, an inhibitor of oxidative stress, N-acetyl cysteine, was shown to dramatically diminish rhododendrol-induced generation of hydroxyl radicals and melanocyte cytotoxicity by increasing glutathione levels. In contrast, buthionine sulfoximine, which depletes glutathione, augmented both of those parameters. Suppressing oxidative stress would prevent and/or mitigate some phenol derivative-induced leukoderma by avoiding hydroxyl radical-initiated melanocyte cytotoxicity.

Background: Dry skin can trigger eczema that affects >10% of the US population. Dressing films have been developed to improve diseased skin, but there is limited knowledge about their effects, especially for dry skin‐related symptoms. We developed an electrospinning method that creates a coating film, called a fine fiber (FF) film, characterized by the production of a transparent, thin, flexible, and adherent membrane on the skin surface.Objective: The aim of this pilot study was to examine the effects of the FF film on dry skin.Methods: Three treatments (lotion only, lotion with the FF film, and lotion with an alternative film) were designed to treat subjects with rough skin on their lower legs. Twenty‐four females were enrolled and used either a water‐based lotion U or a petrolatum‐based lotion P and the FF film for 2 weeks followed by a regression phase for 1 week. Skin hydration and roughness scores were assessed as were the subjects’ perceptions of the effects.Results: When the FF film was applied with lotion U, skin hydration was significantly improved even after 1 week, accompanied by a significant improvement of skin roughness and an increase in skin hydration by the end of the regression phase. An evaluation of moisture permeability suggested that the FF film, especially with lotion U, performed as a semipermeable membrane with optimal moisture healing effects on dry skin.Conclusion: The FF film together with a water‐based lotion is a promising treatment to quickly improve dry skin conditions.

Melanin in the epidermis is known to ultimately regulate human skin pigmentation. Recently, we exploited a phenotypic-based screening system composed of ex vivo human skin cultures to search for effective materials to regulate skin pigmentation. Since a previous study reported the potent inhibitory effect of metformin on melanogenesis, we evaluated several biguanide compounds. The unexpected effect of phenformin, once used as an oral anti-diabetic drug, on cutaneous darkening motivated us to investigate its underlying mechanism utilizing a chemical genetics approach, and especially to identify alternatives to phenformin because of its risk of severe lactic acidosis. Chemical pull-down assays with phenformin-immobilized beads were performed on lysates of human epidermal keratinocytes, and subsequent mass spectrometry identified 7-dehydrocholesterol reductase (DHCR7). Consistent with this, AY9944, an inhibitor of DHCR7, was found to decrease autophagic melanosome degradation in keratinocytes and to intensely darken skin in ex vivo cultures, suggesting the involvement of cholesterol biosynthesis in the metabolism of melanosomes. Thus, our results validated the combined utilization of the phenotypic screening system and chemical genetics as a new approach to develop promising materials for brightening/lightening and/or tanning technologies.