• Bulletin of the Korean Chemical Society
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• 제22권1호
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• pp.97-99
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• 2001

• 대한화장품학회지
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• 제22권2호
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• pp.70-75
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• 1996

DMHF (2.5-dimethyl-4-hydroxy-3[2H]-furanone), an antioxidative compound from the reaction of L-cysteine/D-glucose scavenged efficiently 1,1-diphenyl-2-picryl hydrazyl free radicals. It exhibited an inhibitory effect on the autoxidation of linolenic acid, and the protective effect against UV cytotoxicity in cultured human fibroblast. In addition, DMHF appeared to prevent the cellular melanogenesis in the cultured murine melanoma cells more effectively than kojic acid, a well known inhibitor of melanogenesis, while the former was not so effective as the latter for the inhibition of the tyrosinase. Considering that cellular melanogenesis is a metabolic process triggered by oxidative stress, it ovas tentatively deduced that the antioxidative property of DMHF might afford the effect against cellular pigmentation by alleviating the causative stress. In toxicological tests such as irritation and sensitization, this compound turned out to be safe. The results of this study suggest that DMHF may be a novel inhibitor of melanogenesis, and that night be useful for application in cosmetics.

• 생약학회지
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• 제49권1호
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• pp.65-69
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• 2018

Torilin is a major sesquiterpene of Torilis japonica (Umbelliferae) fruits and known to be a melanogenesis inhibitor. Extraction conditions are important factor for the efficient preparation to save cost and time in economic aspects. For this reason, this study was conducted to optimize the extraction condition for maximal yield of torilin. For optimization, extraction factors such as extraction solvent, extraction temperature and sample/solvent ratio were tested and optimized for maximum yield of torilin using response surface methodology with Box-Behnken design (BBD). The optimal condition was obtained as a EtOAc concentration in MeOH of 31.8%, an extraction temperature at $30.3^{\circ}C$ and a sample/solvent ratio, 1000 mg/2 ml. The torilin yield under optimal conditions was found to be 9.9 mg/g dried samples, which were well-matched with the predicted value of 10.4 mg/g dried samples. These results will provide useful information about optimized extraction conditions for the development of torilin as cosmetic therapeutics to reduce skin hyperpigmentation.

• 약학회지
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• 제57권6호
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• pp.388-393
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• 2013

Previously, we have reported that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, increased melanin synthesis through intracellular $Ca^{2+}$ release in B16 cells. In this study we investigated the possible involvement of nitric oxide (NO) in the mechanism of lovastatin-induced melanogenesis. Lovastatin elevated NO formation in a dose-dependent manner. Treatment with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), precursors of cholesterol, did not significantly alter the lovastatin-induced NO production, suggesting that inhibition of cholesterol metabolism may not be involved in the mechanism of this action of lovastatin. Both NO formation and melanogenesis induced by lovastatin was significantly suppressed by treatment with $N^G$-nitro-L-arginine methyl ester (L-NAME) and 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide (cPTIO), an inhibitor of NO synthase and a NO scavenger, respectively. The lovastatin-induced NO production was significantly affected not by EGTA, an extracellular $Ca^{2+}$ chelator, but by an intracellular $Ca^{2+}$ chelator (BAPTA/AM) and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8). Taken together, these results suggest that lovastatin may induce melanogenesis through NO formation mediated by intracellular $Ca^{2+}$ release in B16 cells. These results further suggest that lovastatin may be a good candidate for the therapeutic application of various hypopigmentation disorders.

• Journal of Applied Biological Chemistry
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• 제64권4호
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• pp.323-331
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• 2021

Lincomycin is a lincosamide antibiotic isolated from the actinomycete Streptomyces lincolnensis. Moreover, it has been found to be effective against infections caused by Staphylococcus, Streptococcus, and Bacteroides fragillis. To identify the melanin-inducing properties of lincomycin, we used B16F10 melanoma cells in this study. The melanin content and intracellular tyrosinase activity in the cells were increased by lincomycin, without any cytotoxicity. Western blot analysis indicated that the protein expressions of tyrosinase, tyrosinase related protein 1 (TRP1) and TRP2 increased after lincomycin treatment. In addition, lincomycin enhanced the expression of master transcription regulator of melanogenesis, a microphthalmia-associated transcription factor (MITF). Lincomycin also increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and decreased the AKT phosphorylation. Moreover, the activation of tyrosinase activity by lincomycin was inhibited by the treatment with SB203580, which is p38 inhibitor. Furthermore, we also found that lincomycin-induced tyrosinase expression was reduced by H-89, a specific protein kinase A (PKA) inhibitor. These results indicate that lincomycin stimulate melanogenesis via MITF activation via p38 MAPK, AKT, and PKA signal pathways. Thus, lincomycin can potentially be used for treatment of hypopigmentation disorders.

• 한국식품과학회지
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• 제28권6호
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• pp.1089-1094
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• 1996

검은툭눈붕어를 이용하여 tyrosinase 저해제가 어체의 melanogenesis에 미치는 영향을 평가하였다. 저해제로는 glutathione, cysteine, benzoic acid를 각각 5, 5, 1 mM씩울 혼합하여 첨가한 식품첨가물 처리구, 표고버섯을 주기질로 하여 Aspergillus oryzae를 발효시켜 얻은 microbial inhibitor 처리구, 설록차, 무, 팽이버섯, red chicory 등 4종의 식물체 추출액 혼합물 처리구로 나누어 효능을 평가하였다. 검은툭눈붕어를 0.9% NaCl 용액에서 일주일간 양식하면서 stress를 가하여 비늘의 melanin 농도를 높이고 다시 민물에 담고 각 처리구의 저해제를 첨가한 용액에서 6일간 양식한 후 가슴 부위, 측선 부위 및 등지느러미의 색을 색도계로 측정하고 현미경으로 melanin을 관찰하였을 때 식품 첨가물 처리구와 microbial inhibitor 처리구의 색은 대조구보다 명도와 yellowness가 높아진 것으로 나타나 melanogenesis 억제 효과가 뚜렷하였다. 한편, 농산물 처리구의 경우에도 미약하지만 효과가 인정되었다. 저해제를 처리한 검은툭눈붕어와 대조구 붕어의 측선 부위 비늘과 등지느러미를 설취하여 현미경으로 관찰한 결과 저해제 처리구에서는 단위 면적당 melanophore의 수가 감소하고 하나의 melanophore의 크기도 작아진 것으로 나타났다.

• 약학회지
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• 제55권6호
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• pp.485-491
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• 2011

Previously, we have reported that apigenin, a natural flavonoid found in a variety of vegetables and fruits, stimulated melanogenesis through the activation of $K^+-Cl^-$-cotransport (KCC) in B16 melanoma cells. In this study we investigated the possible involvement of reactive oxygen species (ROS) in the mechanism of apigenin-induced melanogenesis in B16 cells. Apigenin elevated intracellular ROS level in a dose-dependent manner. Treatment with various inhibitors of NADPH oxidase, diphenylene iodonium (DPI), apocynin (Apo) and neopterine (NP) significantly inhibited both the generation of ROS and melanogenesis induced by apigenin. In addition these inhibitors profoundly inhibited apigenin-induced $Cl^-$-dependent $K^+$ efflux, a hallmark of KCC activity. However, the apigenin-induced ROS generation was not significantly affected by treatment with a specific KCC inhibitor R-(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]acetic acid (DIOA). These results indicate that the ROS production may be a upstream regulator of the apigenin-induced KCC stimulation, and in turn, melanogenesis in the B16 cells. Taken together, these results suggest that the NADPH oxidase-mediated ROS production may play an important role in the apigenin-induced melanogenesis in B16 cells. These results further suggest that NADPH oxidase may be a good target for the management of hyperpigmentation disorders.

• 대한화장품학회지
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• 제20권1호
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• pp.1-13
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• 1994

솔잎으로부터 프리 라디칼 소거 작용이 있는 물질을 분리하고, 여러 기기 분석 결과에 근거하여 4-hydroxy-5-methyl-3[2H]-furanone (HMF) 으로 동정하였다. 이 물질이 1, 1-diphenyl-2-picrylhydrazyl 프리 라디칼에 대한 소거 작용이 공지의 항산화 물질인 a-tocopherol, ascorbic acid와 유사하였다. HMF는 흰쥐 간 microsome분획에서 Fe(II)/ascorbate에 의해 유도된 지질 과산화를 억제하였으며, 배양 fibroblast 세포에서 자외선에 대한 보호효과를 나타내었다. 이 물질은 또한 tyrosine의 효소적 산화와 Dopa의 자동 산화를 억제하였을 뿐만 아니라 배양 murine melanoma 세포에서도 강력한 멜라닌 생성 억제 작용을 보였다. 피부 세포에서의 멜라닌 생성이 산화적 스트레스에 의해 유발되고 또 효소, 비효소적인 산화 반응을 통해 진행된다고 볼 때, HMF는 이러한 각 단계에서 항산화제로 작용하여 궁극적으로 세포에서의 멜라닌 생성을 막는 것으로 추론되었다.

• Journal of Microbiology and Biotechnology
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• 제19권4호
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• pp.368-371
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• 2009

In the course of screening for the melanogenesis inhibitors, aspochalasin I was isolated from solid-state culture of Aspergillus sp. Fb020460. Its structure was determined by spectroscopic analysis including mass spectroscopy and NMR analysis. Aspochalasin I potently inhibited melanogenesis in Mel-Ab cells with an $IC_{50}$ value of $22.4{\mu}M$ without cytotoxicity.

• BMB Reports
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• 제45권12호
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• pp.724-729
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• 2012

In this study, we evaluated the anti-melanogenesis effects of Caffeoylserotonin (CaS) in B16 melanoma cells. Treatment with CaS reduced the melanin content and tyrosinase (TYR) activity in B16 melanoma cells in a dose-dependent manner. CaS inhibited the expression of melanogenesis-related proteins, including microphthalmia-associated transcription factor (MITF), TYR, and tyrosinase-related protein-1 (TRP-1), but not TRP-2. ${\alpha}$-MSH is known to interact with melanocortin 1 receptor (MC1R) thus activating adenylyl cyclase and increasing intracellular cyclic AMP (cAMP) levels. Furthermore, cAMP activates extracellular signal-regulated kinase 2 (ERK2) via phosphorylation, which phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. The CaS reduced intracellular cAMP levels to unstimulated levels and activated ERK phosphorylation within 30 min. The ERK inhibitor PD98059 abrogated the suppressive effect of CaS on ${\alpha}$-MSH-induced melanogenesis. Based on this study, the inhibitory effects of CaS on melanogenesis are derived from the downregulation of MITF signaling via the inhibition of intracellular cAMP levels, as well as acceleration of ERK activation.