Melanin Production In Skin Research Articles

Virtual screening of natural products to enhance melanogenosis.

Natural products have long been an important source of inspiration for medicinal chemistry and drug discovery. In the cosmetic field, they remain the major elements of the composition and serve as marketing asset. Recent research showed the implication of salt-inducible kinases on the melanin production in skin via MITF regulation. Finding new potent modulators on such target could open the way to several cosmetic applications to attenuate visible signs of photoaging and improve the tan without sun. Since virtual screening can be a powerful tool for detecting hit compounds in the early stages of a drug discovery process, we applied this method on salt-inducible kinase 2 to discover potential interesting compounds. Here, we present the different steps from the construction of a database of natural products, to the validation of a docking protocol and the results of the virtual screening. Hits from the screening were tested in vitro to confirm their efficiency and results are discussed.

UV-B-activated B16 melanoma cells or HaCaT keratinocytes accelerate signaling pathways associated with melanogenesis via ANGPTL 2 induction, an activity antagonized by Chrysanthemum extract.

Sunburn causes inflammation, which increases melanin production in skin and causes hyperpigmentation. Angiopoietin‐like protein (ANGPTL) 2 is an inflammatory mediator induced in sun‐exposed skin areas. However, whether ANGPTL2 functions in melanin production remains unclear. To assess this possibility, we overexpressed Angptl2 in the melanoma line B16 and in the keratinocyte line HaCaT. Relative to controls, Angptl2‐expressing B16 cells produced higher melanin levels via tyrosinase induction. Accordingly, Angptl2‐expressing HaCaT cells secreted relatively high levels of both endothelin‐1 (ET‐1) and α‐melanocyte‐stimulating hormone (α‐MSH). Moreover, treatment with an extract from Chrysanthemum indicum × Erigeron annuus (CE) suppressed ANGPTL2 expression and repressed tyrosinase induction in melanocytes and of α‐MSH and ET‐1 in keratinocytes. Our data suggest that ANGPTL2 expression in keratinocytes and melanin‐producing cells accelerates pigment production and that treatment of skin with a CE extract could prevent melanin accumulation.

Protective Effects of Topical Application of a Poorly Soluble Antioxidant Astaxanthin Liposomal Formulation on Ultraviolet-Induced Skin Damage

Astaxanthin (Asx) would be expected to prevent ultraviolet (UV)-induced skin damage, as it is regarded as a potent antioxidative carotenoid in biological membranes. However, it is difficult to administer Asx topically to skin because of its poor water solubility. In this study, we attempted to solve this problem by preparing liposomes containing Asx (Asx-lipo), which were dispersible in the water phase, and therefore, suitable for topical application to the skin. Asx-lipo was shown to have potent scavenging ability against chemiluminescence-dependent singlet oxygen production in the water phase. When Asx-lipo was applied to skin before UV exposure, UV-induced skin thickening was prevented. Interestingly, collagen reduction induced by UV exposure was also prevented by preadministration of Asx-lipo. In addition, topical administration of Asx-lipo containing cationic lipid inhibited melanin production in skin exposed to UV. Consequently, we succeeded in preventing UV-induced skin damage using a topical application of a liposomal formulation containing Asx.

The melanocortin‐1 receptor (MC1R) gene and color polymorphism in Plethodon cinereus

The salamander Plethodon cinereus can be found in two different color phases; the red‐back phase and the lead‐back phase. The molecular basis behind these different color morphs is not fully understood. In this study, the gene for the melanocortin receptor (MC1R) was sequenced to see if mutations in this gene are responsible for these color differences. MC1R is a G protein‐coupled receptor that has seven transmembrane domains. It plays an important role in pigmentation and melanin production in skin, hair and feathers and mutations in this protein appear to correspond to light or dark phenotypes in many different animals. It was hypothesized that mutations in MC1R are responsible for the polymorphism in Plethodon cinereus. Frozen tissue from salamanders caught from Helderberg Escarpment was used to isolate, amplify and sequence 692 base pair fragment of MC1R. Sequencing this gene for MC1R will hopefully help to better understand the molecular basis for the color morphs in Plethodon cinereus. Supported by Union College, Biology Department.

Differential Regulation of Tyrosinase Activity in Skin of White and Black Individuals In Vivo by Topical Retinoic Acid

Tyrosinase activity is a key determinant of melanin production in skin. Because retinoic acid regulates tyrosinase activity in melanoma cells, we analyzed modulation of pigmentation in vivo by retinoic acid. Black and white subjects were either not treated, or treated topically for 4 d under occlusion with vehicle, retinoic acid (0.1%), or the irritant sodium lauryl sulfate (2%). In untreated skin, tyrosinase activity and melanin content were significantly greater (2.3 times, and 3.2 times, respectively) in blacks versus whites. Four days of treatment with topical retinoic acid did not alter tyrosinase activity or melanin content in black skin. In contrast, retinoic acid treatment significantly induced (2.7 times, n = 8) tyrosinase activity, compared to vehicle treatment, in white skin. Melanin content, however, remained unchanged at 4 d. In separate experiments, tyrosinase activity in white subjects (n = 25) was increased 16% (p = 0.01) in sodium lauryl sulfate-treated skin, and 77% (p = 0.0005) in retinoic acid-treated skin, compared to vehicle-treated skin. The effect of retinoic acid on tyrosinase activity could be differentiated from non-specific irritation, because tyrosinase activity in retinoic acid-treated skin was significantly greater (52%, p = 0.004) than sodium lauryl sulfate-treated skin. Similar results were obtained with the dihydroxyphenylalanine reaction done on vehicle, sodium lauryl sulfate-, and retinoic acid-treated white skin. Northern analysis (n = 6) and semi-quantitative polymerase chain reaction (n = 6) demonstrated that retinoic acid treatment did not alter tyrosinase mRNA levels in white skin. Western analysis revealed that induction of tyrosinase activity by retinoic acid also was not associated with increased tyrosinase protein content (n = 9), indicating that regulation of tyrosinase activity by retinoic acid occurs through a post-translational mechanism. These data demonstrate that low tyrosinase activity in white skin in vivo is retinoic acid inducible and high tyrosinase activity in black skin in vivo is neither further induced nor reduced by retinoic acid.