• Proceedings of the PSK Conference
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• 2003.04a
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• pp.267.2-267.2
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• 2003

Melanin biosynthesis inhibitors are useful not only for the materials used in cosmetics as skin-whitening agents but also for the remedy of hyperpigmentation. In order to find the new skin-whitening compounds from the natural products. screening of tyrosinase inhibitory activity in vitro has been carried out. The EtOH extracts of two hundred crude drugs were performed at the concentration of 500 $\mu\textrm{g}$/$m\ell$. (omitted)

• Korean Journal of Pharmacognosy
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• v.30 no.4
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• pp.397-403
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• 1999

Tyrosinase plays an important role in the process of melanin polymer biosynthesis. Therefore, the enzyme inhibitors have been of great concern as cosmetics to have skin-whitening effects on the local hyperpigmentation. During the search for new inhibitory compounds on melanin polymer biosynthesis from natural sources, MeOH extracts of 589 higher plants were tested for the inhibitory effect on tyrosinase activity by the muschroom tyrosinase assay in vitro. Among plants tested, the leaves of Cercis chinensis exhibited potent inhibitory effect on mushroom tyrosinase activity. Subsequently seven active compounds were isolated from the ethyl acetate soluble part of acetone extract of the leaves of C. chinensis by the activity guided fractionation monitoring the inhibitory effect on tyrosinase activity. Their chemical structures were identified as $kaempferol-3-0-{\alpha}-L-rhamnoside$, quercitrin, $myricetin-3-0-{\alpha}-L-rhamnoside$, myricetin-3-0-(2'-O-galloyl)- ${\alpha}$ -L-rhamopyranoside (desmanthin), (-)-epicatechin-3-0-gallate, (-)-epigallocatechin-3-0-gallate, and methyl gallate on the basis of the speculation of spectral data and chemical reaction. Among the flavonol rhamnosides, myricetin-3-0-(2'-O-galloyl)- -L-rhamnoside(desmanthin) showed most potent inhibitory effect on tyrosinase activity and the structure of B-ring in flavonol moiety was related to the activity. (-)-Epigallocatechin-3-O-gallate having pyrogallol group in flavan-3-ol moiety exhibited more potent inhibitory effect than (-)-epicatechin-3-0-gallate having catechol group in flavan-3-ol moiety on mushroom tyrosinase activity.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.714-725
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• 2023

Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

• Proceedings of the KAIS Fall Conference
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• 2012.05a
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• pp.182-186
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• 2012

human tyrosinase (hTyr) catalyzes first and the rate limiting step in the synthesis of polymerized pigment, melanin which determines skin, hair and eye colors. Mutation of hTyr often brings about decrease of melanin production and further albinism. Meanwhile, a number of cosmetic companies providing skincare products for woman in Asia-Pacific region have tried to develop inhibitors to bright skin color for several decades. In this study, we built a 3D structure by comparative modeling technique based on the crystal structure of tyrosinase from bacillus megaterium as a template to serve structural information of hTyr. According to our model and sequence analysis of type 3 copper protein family proteins, two copper atoms of active site located deep inside are coordinated with six strictly conserved histidine residues coming from four-helix-bundle. Cavity which accommodates substrates was like funnel shape of which entrance was wide and expose to solvent. In addition, protein-substrate and protein-inhibitor complex were modeled with the guide of van der waals surface generated by in house software. Our model suggested that only phenol group or its analogs can fill the binding site near nuclear copper center because inside of binding site has narrow shape relatively. In conclusion, the results of this study may provide helpful information for designing and screening new anti-melanogensis agents.

• ALGAE
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• v.30 no.2
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• pp.163-170
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• 2015

Tyrosinase inhibitors are an important component of cosmetic products. Our previous studies have proposed that eckol isolated from the brown alga Ecklonia cava, can be explored as a tyrosinase inhibitor. However, cellular activities and mechanism of action of eckol remain unknown. Therefore, the current study analyzed the eckol binding modes using the crystal structure of Bacillus megaterium tyrosinase. The effects of eckol on melanin synthesis induced by ${\alpha}$-melanocyte stimulating hormone in B16F10 melanoma cells were also investigated. We predicted the 3D structure of tyrosinase and used a docking algorithm to simulate binding between tyrosinase and eckol. These molecular modeling studies were successful (calculated binding energy value, $-115.84kcal\;mol^{-1}$) and indicated that eckol interacts with Asn205, His208, and Arg209. Furthermore, eckol markedly inhibited tyrosinase activity and melanin synthesis in B16F10 melanoma cells. We also found that eckol decreased the expression of tyrosinase, tyrosinase-related protein (TRP) 1, and TRP2. These results indicate that eckol is a potent inhibitor of melanogenesis, and this finding may be useful for the development of novel pharmaceutical and cosmetic agents.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.41 no.1
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• pp.7-12
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• 2008

To develop a whitening agent, cytotoxicity of the soluble collagen isolated from Todarodes pacificus (CIT) was evaluated. CIT tested for cytotoxicity on human dermal fibroblast (CCD-986sk) was exhibited very low cytotoxicity. Because tyrosinase is the key enzyme for melanin biosynthesis, the use of various tyrosinase inhibitors is a common practice for whitening purpose in cosmetics. Tyrosinase inhibitory activity and melanin production assay were measured to confirm the whitening effect. The inhibitory effect of MMP-1 in UV-irradiated human dermal fibroblast was also performed. CIT showed strong inhibition potency on tyrosinase by 51.5% at 0.2 mg/mL which increased the inhibition by increasing the concentration of CIT, and showed 69.1% inhibition at 1.0 mg/mL. CIT showed strong inhibition effect on melanin production with 82% at 1.0 mg/mL. The CIT also reduced about 76% expression of MMP-1 in UV-irradiated CCD-986sk cell at 1.0 mg/mL. From the preliminary observations, we suggest that the collagen isolated from CIT could be a potential source of natural skin-whitening and anti-aging agents for the photo-damaged skin.

• Journal of dental hygiene science
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• v.4 no.2
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• pp.81-84
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• 2004

Gingival hyperpigmentation may cause esthetic problems and embarrassment. Especially in patients with a gummy smile. Melanin pigmentation is related to estiologic factor such as hormon, systemic factor, drug, smoking and gingival inflamation. During our search for new inhibitory components on melanogenesis from natural resources, MeOH extracts of more than 100 higher plants were tested for the inhibitory effect on melanogenesis in cultured B-16 mouse melanoma cell lines, and methylene chloride soluble part extract of Cnidii Rhizoma MeoH extraction was found to have potent activity. Cnidii Rhizoma, the root of Cnidium officinale Makino (Umbelliferae), is used for the treatment of abdominal pain, arthralgia, headache, hypertension, intestinal colic and for menstrual disorders and uterine cramps for its anti-blood stagnation effect. Two compounds were isolated and their chemical structures were determined as linoleic acid methyl ester(1), 1,3-dilinoleoyl-2-stearoyl glycerol(2), on the basis of physical and spectral data.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.3004-3008
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• 2012

Small molecule conjugated peptides were prepared by solid-phase synthesis as potential novel whitening agents, and their melanogenesis inhibitory activities were investigated. The conjugated small molecules were well-known materials as tyrosinase inhibitors, and peptides were selected from the sequences that are known to antagonize melanocortin receptor 1 (MC1R). Most of small molecules-peptide conjugates showed superior melanin inhibition activity to kojic acid and arbutin. Among these, almost all compounds have -AR- sequence. From this study, we concluded that the small molecule conjugated peptides containing -AR- sequence have melanogenesis inhibitory activities and have potential to be used as novel whitening agents.

• Bulletin of the Korean Chemical Society
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• v.31 no.7
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• pp.2036-2038
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• 2010

• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.33-39
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• 2003

Eight compounds were isolated from the roots of Glycyrrhiza glabra by the tyrosinase inhibitory activity guided fractionation, and their structures were identified as liquiritigenin (1), isoliquiritigenin (2), isoliquiritigenin-2'-O-methyl ether (3), liquiritin (4), isoliquiritin (5), ononin (6), glycycoumarin (7), glycyrol (8) by analysis of spectral data. Compound 3 exhibited the most potent inhibitory effect on mushroom tyrosinase activity ($IC_{50}$, 47 M).