Aryl Hydrocarbon Receptor as a Therapeutical Target of Environmentally Induced Skin Conditions.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, expressed in several tissues and involved in the response to environmental stressors. Studies have already associated exposure to environmental factors, such as organic air pollutants, products of the skin microbiota, and solar radiation, with the development/worsening of skin conditions, mediated by AhR. On the other hand, recent studies have shown that synthetic and natural compounds are able to modulate the activation of some AhR signaling pathways, minimizing the harmful response of these environmental stressors in the skin. Thus, AhR constitutes a new therapeutic target for the prevention or treatment of skin conditions induced by the skin exposome. Herein, an overview of potential AhR ligands and their biologic effects in environmentally induced skin conditions are presented. The literature survey pointed out divergences in the mechanism of action from a therapeutic perspective. Although most studies point to the benefits of ligand downregulation of AhR signaling, counteracting the toxic effects of environmental factors on the skin, some studies suggest the AhR ligand activation as a therapeutical mechanism for some skin conditions. Furthermore, both agonist and antagonist profiles were identified in the AhR modulation by the synthetic and natural compounds raised. Despite that, this target is still little explored, and further studies are needed to elucidate the molecular mechanisms involved and identify new AhR ligands with therapeutic potential. SIGNIFICANCE STATEMENT: The aryl hydrocarbon receptor (AhR) is involved in different skin physiological and pathological processes, including toxic mechanisms of environmental factors. Synthetic and natural AhR ligands have demonstrated therapeutic potential for skin conditions induced by these agents. Thus, a comprehensive understanding of the skin toxicity mechanisms involving the AhR, as well as the use of AhR modulators from a therapeutic perspective, provides an alternative approach to the development of new treatments for skin disorders induced by the exposome.

Modulation of skin androgenesis and sebum production by a dermocosmetic formulation.

BACKGROUND: Excessive androgenesis in the skin promotes sebaceous hyperproduction which is the onset of acne vulgaris pathogenesis. Free fatty acids and lipid accumulation in the glandular infundibulum culminates in microbiota imbalance, triggering inflammatory response and follicular hyperkeratinization. AIMS: The purpose of this work was to present an alternative cosmetic treatment for acne skin care, focusing on the prevention of sebaceous gland dysregulation. METHODS: Insulin-stimulated human sebocytes were treated with noncytotoxic concentrations of a DTRW cosmetic formulation. After 6 days of incubation, cell lysates were collected for testosterone, 5α-reductase, and dyhidrotestosterone (DHT) quantitation. In parallel, cells were stained with Oil Red O to measure sebum production. RESULTS: Human sebocytes were incubated with insulin to mimic a seborrheic microenvironment with overproduction of intracellular lipids and fatty acids. Concomitant incubation of cell cultures with DRTW was able to promote a 52.97% reduction in intracellular lipid content. The anti-androgenic properties of DRTW had been proved by the reductions of testosterone (↓59.90%), 5α reductase (↓59.34%), and DHT (↓55.98%) levels in sebocyte cultures also stimulated with insulin. CONCLUSION: The results indicate a promising action of DRTW cosmetic formulation in preventing the development of acne lesions by mechanisms involving the modulation of cutaneous androgenesis and consequently the control of sebum overproduction, considered one of the leading causes of acne.

Whitening effects of cosmetic formulation in the vascular component of skin pigmentation.

BACKGROUND: Melanin plays an important role in protecting the skin against the harmful effects of solar radiation, but its abnormal accumulation may become an aesthetic problem, such as melasma and age spots. AIMS: The aim of this study was to evaluate the antiangiogenic and whitening effects of a depigmentation formulation (BLTX) using an in vitro model of human cell and skin culture. METHODS: Human fibroblasts, keratinocytes or melanocytes were treated with BLTX and subjected to oxidative stress by UV radiation or inflammatory stress with IL-1α for quantification of melanin, tyrosinase, endothelin-1, PAR-2, VEGF and iNOS. Fragments of human skin, from elective plastic surgery, were treated with BLTX and subjected to histological evaluation with hematoxylin/eosin associated with Fontana-Masson technique for melanin view. A parametric method, the one-way analysis of variance (ANOVA) followed by the Bonferroni test, was used to compare data among all groups. RESULTS: The results demonstrated that BLTX promotes a reduction in VEGF and iNOS protein synthesis in cultured dermal fibroblasts, indicating an antiangiogenic property. In relation to whitening effect, BLTX was able to reduce the production of melanin in both systems, melanocytes and human skin cultures. The depigmenting action was also revealed by decreasing the levels of endothelin-1, PAR-2 and activity of tyrosinase, when compared to cultures exposed to UV radiation. CONCLUSION: The results allow us to infer that BLTX presents an antiangiogenic effect indicating a role in the vascular component of melasma. Furthermore, the whitening property observed reinforces its use in the prevention and treatment of melasma.