• Journal of Life Science
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• v.24 no.9
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• pp.946-951
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• 2014

Melanin plays a key role in the protection of skin from ultraviolet light that generates reactive oxygen species (ROS), such as superoxide, hydroxyl radical, singlet oxygen and hydrogen peroxide. However, the ROS leading to the oxidation of lipids, proteins and DNA are involved in the overproduction of melanin that is known to cause melasma, age spots and freckles. Among the herb medicines, Ulmus macrocarpa used in this study was reported to contain flavonoids as a main component. The aim of this study is to investigate the whitening and anti-oxidant effects of Ulmus macrocarpa ethanolic extracts (UMEE) in B16F1 cells. UMEE below $3.12{\mu}g/ml$ did not show cytotoxicity. In an anti-oxidant experiment, UMEE showed not only high reducing power and scavenging activity on DPPH, but it was also observed that UMEE exhibit an inhibitory effect on lipid peroxidation. UMEE did not display an inhibitory effect on tyrosinase activity in vitro. However, UMEE inhibited melanin synthesis in B16F1 cells. In addition, UMEE reduced the expression levels of tyrosinase and tyrosinase-related protein-2 (TRP-2), which are key enzymes in melanogenesis. These results indicate that UMEE exert a whitening effect through the inhibition of both tyrosinase and TRP-2 expressions as well as anti-oxidant activity, suggesting that UMEE could have the functional potential for a whitening effect on the skin.

• Journal of Life Science
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• v.32 no.5
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• pp.331-339
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• 2022

Melanin is a pigment produced by melanocytes to protect the skin from external stimuli, mainly ultraviolet (UV) rays. However, abnormal and excessive production of melanin causes hyperpigmentation disorders, such as freckles, age spots, and discoloration. Natural cosmeceuticals are a new trend for treating or preventing hyperpigmentation due to fewer side effects and biocompatibility. In this context, the current study focused on Cnidium japonicum, a halophyte with several uses in folk medicine, to evaluate its potential as a skin-whitening agent. The effect of C. japonicum extract (CJE) on melanin production was analyzed in melanogenesis-stimulated B16F10 melanoma cells. The results showed that CJE successfully inhibited the oxidation of tyrosine and L-DOPA by tyrosinase and subsequently decreased the production of the key enzymes responsible for melanin production: tyrosinase, tyrosinase-related protein-1, and protein-2. This effect was confirmed by decreased intracellular and extracellular melanin levels in B16F10 melanoma cells after CJE treatment. Further experiments to elucidate the action mechanism revealed that CJE treatment suppressed melanin production by inhibiting the activation of glycogen synthase kinase 3 β (GSKβ)/β-catenin and protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathways, which are the upstream activators of melanogenesis. In conclusion, the present study suggests that C. japonicum is a potential natural source of bioactive substances for the development of novel cosmeceuticals that can act against hyperpigmentation.

• Journal of Life Science
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• v.31 no.8
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• pp.719-728
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• 2021

Melanin pigments are abundantly distributed in mammalian skin, hair, eyes, and nervous system. Under normal physiological conditions, melanin protects the skin against various environmental stresses and acts as a physiological redox buffer to maintain homeostasis. However, abnormal melanin accumulation results in various hyperpigmentation conditions, such as chloasma, freckles, senile lentigo, and inflammatory pigmentation. Tyrosinase, a copper-containing enzyme, plays an important role in the regulation of the melanin pigment biosynthetic pathway. Although several whitening agents based on tyrosinase inhibition have been developed, their side effects, such as allergies, DNA damage, mutagenesis, and cytotoxicity of melanocytes, limit their applications. In this study, we synthesized 4-chromanone derivatives (MHY compounds) and investigated their ability to inhibit tyrosinase activity. Of these compounds, (E)-3-(4-hydroxybenzylidene)chroman-4-one (MHY1294) more potently inhibited the enzymatic activity of tyrosinase (IC₅₀ = 5.1±0.86 μM) than kojic acid (14.3±1.43 μM), a representative tyrosinase inhibitor. In addition, MHY1294 showed competitive inhibitory action at the catalytic site of tyrosinase and had greater binding affinity at this site than kojic acid. Furthermore, MHY1294 effectively inhibited α-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis and intracellular tyrosinase activity in B16F10 melanoma cells. The results of the present study indicate that MHY1294 may be considered as a candidate pharmacological agent and cosmetic whitening ingredient.

• Journal of Life Science
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• v.33 no.2
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• pp.169-175
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• 2023

As a protective defensive mechanism against ultraviolet (UV) light exposure in skin tissue, melanocytes produce the pigment melanin. Tyrosinase plays a key role in melanin production in melanocytes. However, the overproduction of melanin can lead to lesions, such as freckles and dark spots. Thus, it is clinically important to find a modulating molecule to control melanogenesis by regulating tyrosinase expression and/or activity. It is known that catechin, a plant flavonoid, can reduce melano- genesis through the downregulation of tyrosinase expression. Here, we tested whether catechin derivatives isolated from the stem bark of Ulmus parvifolia have an effect on melanin production by regulating tyrosinase in mouse melanoma cells and in vitro mushroom tyrosinase. The catechin derivatives used in this study included C5A, C7A, C7G, and C7X. Treatments using these catechin derivatives reduced melanin production in mouse melanoma B16F10 cells in which melanogenesis was stimulated by α-MSH. Notably, the anti-melanogenic effects of catechin derivatives were similar to those of kojic acid, a well-known anti-melanogenic molecule. Both C5A and C7A directly inhibited the activity of tyrosinase isolated from mushrooms in vitro. Furthermore, our in silico computational simulation showed that these two compounds were expected to bind to the active site of tyrosinase, which is similar to kojic acid. In addition, all four catechin derivatives reduced tyrosinase protein expression. In summary, our results showed that catechin derivatives can reduce melanogenesis by regulating tyrosinase activity or expression. Thus, this study suggests that catechin derivatives isolated from U. parvifolia can be novel modulators of melanin production.