• Genomics & Informatics
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• v.21 no.3
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• pp.43.1-43.13
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• 2023

Melanin is synthesized by tyrosinase to protect the skin from ultraviolet light. However, overproduction and accumulation of melanin can result in hyperpigmentation and skin melanoma. Tyrosinase inhibitors are commonly used in the treatment of hyperpigmentation. Natural tyrosinase inhibitors are often favoured over synthetic ones due to the potential side effects of the latter, which can include skin irritation, allergies, and other adverse reactions. Nuciferine, an alkaloid derived from Nelumbo nucifera, exhibits potent antioxidant and anti-proliferative properties. This study focused on the in silico screening of nuciferine for anti-tyrosinase activity, using kojic acid, ascorbic acid, and resorcinol as standards. The tyrosinase protein target was selected through homology modeling. The residues of the substrate binding pocket and active site pockets were identified for the purposes of grid box optimization and docking. Therefore, nuciferine is a potent natural tyrosinase inhibitor and shows promising potential for application in the treatment of hyperpigmentation and skin melanoma.

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1226-1232
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• 2004

Extracts from seventeen seaweeds were determined for tyrosinase inhibitory activity using mushroom tyrosinase with L-tyrosine as a substrate. Only one of them, Ecklonia stolonifera OKAMURA (Laminariaceae) belonging to brown algae, showed high tyrosinase inhibitory activity. Bioassay-guided fractionation of the active ethyl acetate (EtOAc) soluble fraction from the methanolic extract of E. stolonifera, led us to the isolation of phloroglucinol derivatives [phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5)]. Compounds 1~5 were found to inhibit the oxidation of L-tyrosine catalyzed by mushroom tyrosinase with $IC_{50}$ values of 92.8, 126, 33.2, 177, and 2.16 ${\mu}g$ /mL, respectively. It was compared with those of kojic acid and arbutin, well-known tyrosinase inhibitors, with $IC_{50}$ values of 6.32 and 112 ${\mu}g$ / mL, respectively. The inhibitory kinetics analyzed from Lineweaver-Burk plots, showed compounds 1 and 2 to be competitive inhibitors with $K_i$ of $2.3{\times}10^{-4}\;and\;3.1{times}10^{-4}$ M, and compounds 3~5 to be noncompetitive inhibitors with $K_i$ of $1.9{\times}10^{-5},\;1.4{\times}10^{-3}\;and\;1.5{\times}10^{-5}$ M, respectively. This work showed that phloroglucinol derivatives, natural compounds found in brown algae, could be involved in the control of pigmentation in plants and other organisms through inhibition of tyrosinase activity using L-tyrosine as a substrate.

• Korean Journal of Plant Resources
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• v.14 no.1
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• pp.32-37
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• 2001

Mammalian tyrosinase plays an important role in the process of melanin polymer biosynthesis by catalyzing the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine(DOPA) and the oxidation of DOPA to dopaquinone. These processes are major determinant of human skin color and involved in localized hyperpigmentation. Therefore, the enzyme inhibitors have been of great concern as skin-whitening cosmetics. Methanol extracts of 174 oriental herbs were screened for the mushroom tyrosinase inhibitory activity.

• YAKHAK HOEJI
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• v.41 no.4
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• pp.456-461
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• 1997

Tyrosinase is known to accelerate the melanin polymer biosynthesis in melanocyte, so tyrosinase inhibitors hinder the melanin polymer biosynthesis and are useful not only for th e material used in cosmetics as skin-whitening agents but also as the remedy for disturbances in pigmentation. During our search for new melanin biosynthesis inhibitors from natural sources, 130 higher plants were tested for the inhibitory effect against tyrosinase activity by the mushroom tyrosinase assay. Among them, Carex humilis ($IC_{50}$, 10vg/ml), Sophora flavescence ($IC_{50},\;20{\sim}50{mu}g/ml$) and Styrax japonica ($IC_{50},\;10{\mu}g/ml$) inhibited the tyrosinase activity strongly.

• Food Science and Preservation
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• v.7 no.4
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• pp.409-413
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• 2000

Previously, the methanolic extracts of thirty Korean medicinal plant seeds were screened for tyrosinase inhibitors using a rapid and simple TLC method, which was superior to a conventional spectrophotometrical in vitro assay. As a result, the methanolic extracts of Thuja orientalis seeds was found to have strong tyrosinase inhibitory activity. To isolate active tyrosinase inhibitors, the seeds were defatted with n-hexane under reflux, and then extracted twice with methanol under reflux at 90$^{\circ}C$. The methanolic extract was evaporated to a small volumn in vacuo, and then successively fractionated with ether, ethyl acetate and n-butanol. The ether extract showing significant tyrosinase inhibitory activity was solubilized with 5% NaHCO$_3$and then acidified with 6N HCI. The ether souble acidic fraction was successively ohromatographed on silica gel, Sephadex LH-20 and preparative TLC. Among four compounds isolated, two of them showed stronger tyrosinase inhibitory activity, comparable to that of L-ascorbic acid (IC$\sub$50/=28$\mu\textrm{g}$/$m\ell$). These results suggest that Thuja orientalis seeds may be useful as potential sources of antibrowning agents in fruits and vegetables, and anti-melanoma agents in cosmetics and phamaceuticals.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1132-1135
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• 2004

In order to find new tyrosinase inhibitors and the effects of prenyl residue on flavonoid molecules, eight prenylated and three synthetic vinylated flavonoids were examined on their inhibitory effect against tyrosinase activity. From the results, kuwanon C, papyriflavonol A, sanggenon D and sophoflavescenol were found to possess the considerable inhibitory activity. Especially, sanggenon D is revealed as a potent inhibitor ($IC_{50}$ =7.3$\mu$ M), compared to the reference compound, kojic acid ($IC_{50}$ =24.8 $\mu$M). However, the prenylation with isoprenyl group or the vinylation to flavonoid molecules did not enhance tyrosinase inhibitory activity.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.321.1-321.1
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• 2002

To indentify inhibitors of melanogenesis. we compared the effect of some natural products on mushroom tyrosinase. human melanocytic tyrosinase activity and melanin content. The cytotoxicity of the component were also tested on cultured mouse melanoma cells, Each extract significantly inhibited tyrosinase activity and melanin synthesis in vitro and B 16 melanoma cell lines. In B 16 cell lines, watermelon's inner shell extract inhibited tyrosinase activity as strong as kojic acid at 150${\um}g$/${\mu}\ell$ concentration. And morning glory'seed extract inhibited melanin synthesis more than kojic acid at 150${\um}g$/${\mu}\ell$ concentration. Each extract were strong inhibitors of tyrosinase activity and total melanin synthesis in B 16 mouse melanoma cell lines at less than 100${\um}g$/${\mu}\ell$ concetration. These result show that extract of watermelon's inner shell. lettuce. morning glory's seed and licorice root could be developed as skin whitening component of cosmetics.

• Natural Product Sciences
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• v.17 no.1
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• pp.26-32
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• 2011

Novel tyrosinase inhibitors are important for pigmentation in the skin. Following extraction of tyrosinase inhibitors from edible vegetables or fruits, we found that the Prunus persica flesh extract (PPFE) exhibited potential inhibitory activity for melanogenesis. PPFE showed tyrosinase inhibitory activity in an enzymatic assay and PPFE also significantly inhibited the melanin formation in cultured mouse melan-a cells. Moreover, real-time RT-PCR analysis revealed that the inhibition of melanin production by PPFE was closely related to marked suppression of mRNA expression of tyrosinase and tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2) in melan-a cells. Further investigation found that the modulation of tyrosinase expression by PPFE was associated with the transcriptional regulation of the microphthalmia-associated transcription factor (MITF). PPFE inhibited the promoter activity of MITF and suppressed MITF mRNA expression in melan-a cells. These results indicate that PPFE down-regulates melanogenesis-associated gene expression through MITF-mediated transcriptional regulation and these events might be related to the hypopigmentary effects of PPFE.

• Natural Product Sciences
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• v.10 no.2
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• pp.80-84
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• 2004

Rosmarinic acid and its methyl ester, isolated from the ethyl acetate soluble fraction of the methanolic extract of Salvia miltiorrhiza Bunge (Labiatae), were found to inhibit the oxidation of L-tyrosine catalyzed by mushroom tyrosinase with the $IC_{50}$ values of 16.8 and $21.5\;{\mu}M$, respectively. It was comparable with kojic acid, a well-known tyrosinase inhibitor, with an $IC_{50}$ of $22.4\;{\mu}M$. The inhibitory kinetics analyzed by the Lineweaver-Burk plots, were found rosmarinic acid and its methyl ester to be competitive inhibitors with $K_i\;of\;2.4{\times}10^{-5}\;and\;1.5{\times}10^{-5}\;M$, respectively.

• Korean Journal of Food Science and Technology
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• v.28 no.6
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• pp.1089-1094
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• 1996

The in vivo effect of tyrosinase inhibitors in the melanogenesis of gold fish (jet black color) was evaluated by measuring surface color and observing melanin pigment. The fish was firstly cultivated in 0.9% NaCl solution for 1 week to induce melanogenesis, and then, it was transferred to each treatment group containing tyrosinase inhibitor. The fish was grouped into control. food additive group (addition of 5 mM glutathione, 5 mM cysteine, and 1 mM benzoic acid), microbial inhibitor group (addition of culture broth of Aspergillus oryzae in shiitake and glucose medium), and plant extract group (addition of the mixed extracts of green tea, beet, red chicory, and nameko). After 6 days, the fish was anesthetized by electric shock, and color of pectoral region, lateral region, and dorsal fin was measured. Hunter's L and b values of treated group were generally higher than those of control group, indicating that the tyrosinase inhibitors could inhibit the melanogenesis of the fish. Effect of plant extract was apparent, though relatively weak, not because it did not work in vivo, but because a sufficient amount of extract could not be added to fish globes. If a large amount of extract was added, fish gradually died due to a microbial contamination. Microscopic observation of melanin in lateral scale and dorsal fin showed that in the treated groups with tyrosinase inhibitors, the number of melanophore per unit area and the size of one melanophore decreased.