• Journal of Applied Biological Chemistry
• /
• v.65 no.4
• /
• pp.299-306
• /
• 2022

In this study, derivatives of trimethoxybenzene were investigated as inhibitors of melanogenesis. We examined the effects of methyl 3,4,5-trimethoxybenzoate (MTB), ethyl 3,4,5-trimethoxybenzoate (ETB), methyl 3,4,5-trimethoxycinnamate (MTC), and ethyl 3,4,5-trimethoxycinnamate (ETC). First, the inhibitory effects of these agents on melanin production were evaluated using α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 melanoma cells. We found that all derivatives decreased α-MSH-induced melanin production in B16F10 melanoma cells; ETC showed a strong inhibitory effect at half of the concentration of the other derivatives. As tyrosinase is considered a key enzyme of melanogenesis, we also examined whether the derivatives inhibited tyrosinase activity. MTC and ETC reduced mushroom tyrosinase activity and expression levels of α-MSH-induced B16F10 cellular tyrosinase protein. Inhibitory effects of all derivatives on α-MSH-induced B16F10 cellular tyrosinase activity were shown in a dose-dependent manner. Additionally, the derivatives were exposed to diphenylpicrylhydrazyl free radical to examine their antioxidant characteristics. All derivatives showed considerable antioxidant activity, which was 2-fold higher than that of arbutin. In conclusion, the trimethoxybenzene derivatives, including MTB, ETB, MTC, and ETC exerted anti-melanogenic and antioxidant effects on α-MSH-stimulated melanogenesis, demonstrating their potential for use as novel hypopigmenting agents and antioxidants.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.49 no.4
• /
• pp.307-312
• /
• 2023

Water chestnut is fruits of Trapa natans var. bispinosa grown wild in Korea. In this study, water chestnut was investigated for anti-pigmentation. Treatment with ethanolic extracts of water chestnut significantly reduced production of melanin in α-MSH simulated B16F10 cells. At 200 ㎍/mL ethanolic extracts of water chestnut, melanin contents were repressed by 43.26% compared to the control group. Additionally, ethanolic extracts of water chestnut reduced expression and activity of tyrosinase, key enzyme in melanogenesis, in α-MSH simulated B16F10 cells. Ethanolic extracts of water chestnut downregulated tyrosinase activity and expression to 23.65% and 62.35%, respectively. These results suggest that ethanolic extracts of water chestnut might be used as a promising whitening ingredients for inhibition of α-MSH-induced melanin synthesis and pigmentation.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2022.09a
• /
• pp.118-118
• /
• 2022

Carex pumila Thunb. is a plant native to East Asia, Australia, and New Zealand. However, its effect on skin melanogenesis has not been investigated. In the present study, we evaluated its anti-melanogenic properties using B16F10 melanoma cells and zebrafish larvae in the presence or absence of α-melanocyte stimulating hormone (α-MSH). In this study we revealed that concentrations below 50 µg/mL did not induce any cytotoxicity in B16F10 melanoma cells and cardiotoxicity in zebrafish larvae. However, 50 µg/mL treatment significantly inhibited α-MSH-induced extracellular (from 181.24% α 0.62% to 105.15% α 0.31%) and intracellular melanin contents (from 119.8% α 1.2% to 53.4% α 1.7%) as well as intracellular tyrosinase activity (from 143.9% α 4.2% to 103.7% α 1.4%) in B16F10 melanoma cells. At 25 µg/mL and 50 µg/mL concentrations, it could significantly inhibit α-MSH induced hyperpigmentation in zebrafish larvae (from 100% α 2.3% to 60.7% α 1.3% and 47.5% α 1.9% respectively). Additionally, the extract suppressed α-MSH-induced cAMP-CREB-MITF signaling pathway and consequently inhibited tyrosinase expression in B16F10 melanoma cells. In conclusion, our results indicate that this plant extract could suppress the cAMP-CREB-MITF axis which consequently inhibits tyrosinase mediated melanogenesis.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2021.04a
• /
• pp.49-49
• /
• 2021

The roots of reed (Phragmites australis) were used in traditional medicine to treat respiratory problems, including symptoms such as high fever and cough. In this study, we identified the active ingredient from 70% EtOH reed root extract, and evaluated the whitening, wrinkle improvement and moisturizing effects. The content of p-coumaric acid, the active ingredient of the roots of P. australis, was slightly lower in 70% EtOH extract than in 100% EtOH extract. However, 70% EtOH reed root extract showed similar or higher effect in reducing power, DPPH, hydrogen peroxide scavenging, and nitric oxide scavenging activity compared to 100% EtOH extract. Moreover, 70% EtOH reed root extract markedly inhibited melanogenesis in B16F10 cells treated with α-melanocyte-stimulating hormone. 70% EtOH reed root extract significantly inhibited the mRNA expression of matrix metalloproteinase-1 (MMP-1) and reduced elastase activity in HDF human dermal fibroblasts. In addition, 70% EtOH reed root extract ameliorated hyaluronic acid synthase-2 (HAS-2) expression induced by ultraviolet B (UVB) stimulation in HaCaT keratinocytes. The results of this study suggest that 70% EtOH reed root extract has potential as a functional cosmetic material related to whitening, wrinkle improvement, and moisturizing.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.46 no.1
• /
• pp.34-38
• /
• 2017

Myelophycus simplex Papenfuss, a type of brown algae, is known to be majorly distributed in along the southern coast of Korea and Japan. The purpose of this study was to investigate the effects of M. simplex Papenfuss methanol extract (MSPME) on melanogenesis in ${\alpha}$-melanocyte-stimulating hormone-stimulated B16F10 melanoma cells. Melanin contents of B16F10 melanoma cells were decreased by 27, 41, and 59% in a dose-dependent manner, upon MSPME treatment at 100, 300, and $500{\mu}g/mL$, respectively. Tyrosinase activities in B16F10 melanoma cells were decreased by 18, 49, and 61% in a dose-dependent manner, upon MSPME treatment at 100, 300, and $500{\mu}g/mL$, respectively. MSPME suppressed expression of tyrosinase, tyrosinase-related protein-1, tyrosinase-related protein-2, and melanocyte-inducing transcription factor in B16F10 melanoma cells. Concentration of $50{\mu}g/mL$ of MSPME especially induced greater decreases in tyrosinase activity, melanin contents, and melanogenic enzyme protein expressions. This results indicate that MSPME inhibits melanin synthesis and tyrosinase activity, and M. simplex Papenfuss extract may be an ideal candidate as a skin whitening agent.

• Applied Chemistry for Engineering
• /
• v.25 no.5
• /
• pp.468-473
• /
• 2014

Dendropanax morbifera (D. morbifera) grows in the southern coastal areas and on Jeju Island in Korea. In this study, D. morbifera leaf extract was investigated to determine the mechanism of its whitening effect. The inhibitory activities of the extract on melanogenesis were tested in B16 melanoma cells treated with the ${\alpha}$-melanocyte stimulating hormone (${\alpha}$-MSH). D. morbifera leaf extracts remarkably decreased the melanin content at 25 and $50{\mu}g/mL$. The extracts significantly inhibited the intracellular tyrosinase activity and protein expression of tyrosinase and tyrosinase related protein-2 (TRP-2). In conclusion, D. morbifera leaf extracts would show a whitening effect by inhibiting intracellular tyrosinase activities and the expression of enzymes directly involved in the melanin biosynthesis. The results indicate that fractions of D. morbifera leaf extracts show potential for application as a whitening agent in the new whitening cosmetics.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.38 no.3
• /
• pp.247-254
• /
• 2012

Ramalin (${\gamma}$-glutamyl-N'-(2-hydroxyphenyl)hydrazide) isolated from the Antarctic lichen Ramalina terebrata has been shown to have strong antioxidant activities in the previous study. To investigate additional activities of ramalin, we studied the effects of ramalin on melanogenesis in melan-a cells, a non-tumorigenic melanocyte cell line. At a non-cytotoxic concentration, ramalin dramatically decreased melanin synthesis in melan-a cells in a dose-dependent manner, which was more potent than arbutin, a well-known tyrosinase inhibitor. Ramalin inhibited cell-free tyrosinase activity directly and intracellular tyrosinase activity as well. Its inhibitory mechanisms on melanin production were further assessed, and we found that ramalin significantly decreased the protein levels of melanogenic enzymes such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). However, the mRNA levels of these enzymes were not altered. In a clinical study, application of 0.2 % ramalin on human skin significantly improved the degree of skin brightness after 3 weeks. In conclusion, ramalin has strong anti-melanogenic activity that is exerted both by the direct inhibition of tyrosinase activity and by down-regulation of melanogenic proteins. Furthermore, ramalin showed skin brightening effect in a clinical study. Collectively, these results suggest that ramalin may be a useful inhibitor for melanogenesis in skin.

• Journal of Haehwa Medicine
• /
• v.21 no.1
• /
• pp.125-133
• /
• 2012

본 논문은 피부미백에 관한 실험적 연구로서, 봉선화(Impatiens balsamina Linne)의 성분 중에서 하이드록시-나프타-퀴논(hydroxynaphthoquinone)이 멜라닌 생성억제 효능, 색소침착 저해 효과 등의 미백 활성이 있는 것으로 밝혀졌다. 피부흑화(melanogenesis)는 멜라닌 색소생성세포(melanocyte)에서 자외선 등의 자극에 대한 방어기작으로 멜라닌 생성 활동이 증가되고 이로 말미암아 만들어진 다량의 멜라닌이 각질형성세포(keratinocyte)로 전이되어 피부 표피층에 축척된 결과이다. 비록 멜라닌이 피부에 보호작용을 하나 피부의 과색소 침착은 기미, 주근깨, 피부염증 후의 피부흑화, 노인성 색소반점 등을 일으키며 이로 인해 피부미용 상의 불편뿐만 아니라 정신적으로 부정적인 영향을 미쳐 사회활동에 불편을 초래하기도 한다. 멜라닌 생성 과정은 아미노산의 일종인 티로신(tyrosine)에 티로시나제(tyrosinase)라는 효소가 작용하여 도파(DOPA), 도파퀴논(dopaquinone)으로 바뀐 후 비효소적인 산화 반응을 거쳐 만들어 지며, 이것이 피부 내에 이상 침착하여 기미, 검버섯 등이 생기는 것이라고 알려져 있다. 이와 같은 색소침착, 기미, 반점 등의 완화, 예방 및 치료에는 멜라닌 생성을 억제하는 물질, 예를 들면 하이드로퀴논(hydroquinone), 알부틴, 비타민 C 및 그 유도체 등이 개발되어 사용되고 있으나 이 중, 하이드로퀴논은 일단 효과가 인정되고 있지만 감작성이 있기 때문에 일반적으로 사용이 제한되고 있다. 아스콜빈산은 쉽게 산화되어, 이를 배합한 제품에는 변색, 변취가 되는 문제를 야기하고, 식물추출물 유래의 물질들은 식물의 산지에 따라 효능의 차이가 심하여 제품의 균질성이 유지되기 어렵다. 이러한 이유로 많은 멜라닌 생성을 억제하는 물질을 개발하기 위한 연구들이 계속 진행하고 있다. 2-히드록시-[1,4]나프토퀴논 유도체는 다음과 같은 구조를 나타낸다. 상기 구조에서 R은 포화 혹은 불포화된 직쇄 또는 분지쇄의 알킬로서, 바람직하게는 C1 내지 C10의 포화 혹은 불포화된 직쇄 또는 분지쇄의 알킬이고, 보다 바람직하게는 C1 내지 C5의 포화 혹은 불포화된 직쇄 또는 분지쇄의 알킬이다. 실험에 활용된 화합물은 다음과 같은 반응식으로 얻어졌다. 2-히드록시-[1,4]나프토퀴논과 포타슘카보네이트(K2CO3)를 아세토니트릴에 용해한 후, 저온수조로 냉각하고 알킬할라이드를 적당한 당량비로 천천히 적하하여 히드록시기와 에테르(ether) 반응을 통하여 얻어질 수 있다. 상기 반응식에서 R은 C1~10의 포화 또는 불포화된 알킬기로서 직쇄형 또는 분지쇄형 모두 가능하다. 상기 화합물인 2-히드록시-[1,4]나프토퀴논(2-hydroxynaphthoquinone)은 배양된 쥐의 멜라노마 세포에 대하여 하이드로퀴논과 대등한 멜라닌 생성 억제효과를 보였다. 하이드로퀴논은 저농도에서 강력한 멜라닌 생성 억제효과를 보이지만 상기 화합물들은 보다 낮은 농도에서도 세포독성을 나타내지 않으며 하이드로퀴논보다 높은 멜라닌 생성 억제 효과를 보였다.

• Journal of Radiation Protection and Research
• /
• v.33 no.3
• /
• pp.87-91
• /
• 2008

We induced the activation of melanocytes in the epidermis of C57BL/6 mice by ultraviolet B (UVB) irradiation and observed the effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) on the formation, and decrease of UVB-induced epidermal melanocytes. C57BL/6 mice were irradiated by UVB $80\;mJ/cm^2$ (0.5 mW/sec) daily for 7 days, and BZYQT was intraperitoneally or topically applied pre- or post-irradiation. For the estimation of change of epidermal melanocytes, light microscopic observation with dihydroxyphenylalanine (DOPA) stain was performed. Split epidermal sheets prepared from the ear of untreated mice exhibited 11-16 melanocytes/$mm^2$, and one week after UV irradiation, the applied areas show an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal or topical treatment with BZYQT before each irradiation interrupted UVB-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to radiation control skin. The number and size of DOPA-positive epidermal melanocytes were also significantly decreased in intraperitoneally injected or topically applicated group after irradiation with BZYQT at 3rd and 6th weeks after irradiation. The present study suggests the BZYQT as inhibitor of UVB-induced pigmentation and depigmenting agent.

• KSBB Journal
• /
• v.25 no.4
• /
• pp.330-336
• /
• 2010

In this study, a new compound, 1-(2-hydroxy-3,4,5,6-tetramethoxyphenyl)-1-methoxy-3-phenylpropane; (Jeju-Erythrane) was isolated and identified from the bark of Lindera erythrocarpa Makino. Also, we investigated the effects of Jeju-Erythrane on alpha melanocyte-stimulating hormone (MSH)-induced melanogenesis in mouse B16F10 melanoma cells. The new compound dose dependently inhibited the tyrosinase activity and melanin synthesis in B16F10 cells. The new compound showed inhibitory effect on the Tyrosinase and TRP-1 gene transcription but not on the TRP-2 gene. These results suggest that the new compound of L. erythrocarpa could be used as a functional biomaterial in developing skin whitening agent.