ABSTRACT
BACKGROUND: Solar radiation causes skin damage through the generation of reactive oxygen species (ROS). While UV filters effectively reduce UV-induced ROS, they cannot prevent VIS-induced (400-760 nm) oxidative stress. Therefore, potent antioxidants are needed as additives to sunscreen products. METHODS: We investigated VIS-induced ROS formation and the photoprotective effects of the Nrf2 inducer Licochalcone A (LicA). RESULTS: Visible spectrum of 400-500 nm dose-dependently induced ROS in cultured human fibroblasts at doses equivalent to 1 hour of sunshine on a sunny summer day (150 J/cm2 ). A pretreatment for 24 hours with 1 µmol/L LicA reduced ROS formation to the level of unirradiated cells while UV filters alone were ineffective, even at SPF50+. In vivo, topical treatment with a LicA-containing SPF50 + formulation significantly prevented the depletion of intradermal carotenoids by VIS irradiation while SPF50 + control did not protect. CONCLUSION: LicA may be a useful additive antioxidant for sunscreens.
Subject(s)
Antioxidants , Dermis/metabolism , Fibroblasts/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Sunlight/adverse effects , Sunscreening Agents , Antioxidants/chemistry , Antioxidants/pharmacology , Chalcones/chemistry , Dermis/pathology , Fibroblasts/pathology , Glycyrrhiza/chemistry , Humans , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Sunscreening Agents/chemistry , Sunscreening Agents/pharmacologyABSTRACT
Tyrosinase is the rate-limiting enzyme of melanin production and, accordingly, is the most prominent target for inhibiting hyperpigmentation. Numerous tyrosinase inhibitors have been identified, but most of those lack clinical efficacy because they were identified using mushroom tyrosinase as the target. Therefore, we used recombinant human tyrosinase to screen a library of 50,000 compounds and compared the active screening hits with well-known whitening ingredients. Hydroquinone and its derivative arbutin only weakly inhibited human tyrosinase with a half-maximal inhibitory concentration (IC50) in the millimolar range, and kojic acid showed a weak efficacy (IC50 > 500 µmol/L). The most potent inhibitors of human tyrosinase identified in this screen were resorcinyl-thiazole derivatives, especially the newly identified Thiamidol (Beiersdorf AG, Hamburg, Germany) (isobutylamido thiazolyl resorcinol), which had an IC50 of 1.1 µmol/L. In contrast, Thiamidol only weakly inhibited mushroom tyrosinase (IC50 = 108 µmol/L). In melanocyte cultures, Thiamidol strongly but reversibly inhibited melanin production (IC50 = 0.9 µmol/L), whereas hydroquinone irreversibly inhibited melanogenesis (IC50 = 16.3 µmol/L). Clinically, Thiamidol visibly reduced the appearance of age spots within 4 weeks, and after 12 weeks some age spots were indistinguishable from the normal adjacent skin. The full potential of Thiamidol to reduce hyperpigmentation of human skin needs to be explored in future studies.
Subject(s)
Enzyme Inhibitors/pharmacology , Fungal Proteins/chemistry , Hyperpigmentation/drug therapy , Melanins/metabolism , Monophenol Monooxygenase/antagonists & inhibitors , Skin Lightening Preparations/pharmacology , Agaricales/chemistry , Aged , Animals , Drug Evaluation, Preclinical/methods , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/chemistry , Female , Fungal Proteins/antagonists & inhibitors , Fungal Proteins/metabolism , HEK293 Cells , High-Throughput Screening Assays/methods , Humans , Inhibitory Concentration 50 , Male , Middle Aged , Molecular Docking Simulation , Molecular Structure , Monophenol Monooxygenase/chemistry , Monophenol Monooxygenase/isolation & purification , Monophenol Monooxygenase/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Skin/drug effects , Skin/metabolism , Skin Aging/drug effects , Skin Aging/physiology , Skin Lightening Preparations/administration & dosage , Skin Lightening Preparations/chemistry , Species Specificity , Substrate Specificity , Tissue Culture Techniques , Treatment OutcomeABSTRACT
Individuals differ in the extent to which they are interested in sexualized violence, as displayed in the frequent but not ubiquitous sexual interest in consensual acts of violent sexual role play and violent pornographic media in the normal population. The present research sought to develop and validate a multi-method assessment battery to measure individual differences in the preference for sexualized violence. Three indirect measures (Implicit Association Test, Semantic Misattribution Procedure, Viewing Time) were combined in an online study with 107 men and 103 women. Participants with and without an affiliation with sadomasochistic sexual interest groups were recruited on corresponding Internet platforms. Results revealed that all 3 indirect measures converged in predicting self-reported sexual interest in non-consensual sexuality. Specifically, for men all indirect measures were related to non-consensual sadistic sexual interest, whereas for women an association with masochistic sexual interest was found. Stimulus artefacts versus genuine gender differences are discussed as potential explanations of this dissociation. An outlook on the usability of the assessment battery in applied settings is delivered.
