• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.15-26
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• 2021

Peptides are short chain of amino acids linked by peptide bonds. They are widely used as effective and biocompatible active ingredients in cosmetic industry. In this study, we developed novel peptide mixture and identified its anti-pigmentation effect on melanocytes and keratinocytes. Our results revealed that peptide mixture inhibited melanosome biogenesis through the regulation of microphthalmia-associated transcription factor, a key factor of melanogenesis in melanocytes. And we observed that peptide mixture inhibited melanosome uptake through the reduction of protease-activated receptor 2, a phagocytosis-related receptor in keratinocytes. Furthermore, peptide mixture activated autophagy system resulting in degradation of transferred melanosomes in keratinocytes. The anti-pigmentation effect of multi-targeting peptide mixture was assessed in a human skin equivalent model (MelanoDerm). Melanin contents in epidermal layer were significantly decreased by topical treatment of peptide mixture, suggesting that it can be applied as a novel cosmetics material having a whitening function.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.520-539
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• 2003

By using sequentially efficacy tests based on tyrosinase, the key enzyme of melanogenesis, then a cell line of melanocytes cultured in vitro, we have been able to detect the whitening potential of a plant extract and then to develop a new whitening Active Ingredient whose the whitening potential was confirmed on cultured melanocytes. Through a phytochemical approach, it seems that the whitening potential could be due to the "tannin" fraction of plant extract. A complementary work is planned to explain more precisely which fractions are responsible for the whitening potential and a clinical test is in progress on 30 Asian skin type volunteers to show the whitening efficacy on human volunteers.

• Journal of Ginseng Research
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• 제45권5호
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• pp.555-564
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• 2021

Background: Ginsenosides of Panax ginseng are used to enhance skin health and beauty. The present study aimed to investigate the potential use of ginsenoside Rf (Rf) from Panax ginseng as a new anti-pigmentation agent. Methods: The anti-melanogenic effects of Rf were explored. The transcriptional activity of the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and the expression levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related proteins (Tyrps) were evaluated in melanocytes and UV-irradiated ex vivo human skin. Results: Rf significantly inhibited Forskolin (FSK) or UV-stimulated melanogenesis. Consistently, cellular tyrosinase activity and levels of MITF, tyrosinase, and Tyrps were downregulated. Furthermore, Rf suppressed MITF promoter activity, which was stimulated by FSK or CREB-regulated transcription coactivator 3 (CRTC3) overexpression. Increased CREB phosphorylation and protein kinase A (PKA) activity induced by FSK were also mitigated in the presence of Rf. Conclusion: Rf can be used as a reliable anti-pigmentation agent, which has a scientifically confirmed and reproducible action mechanism, via inhibition of CREB/MITF pathway.

• 대한화장품학회지
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• 제26권1호
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• pp.149-162
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• 2000

Coenzyme Q10(CoQ10)은 피부를 포함한 모든 생체조직에 존재하는 널리 알려진 조효소이다. 전자전달에 관여하는 퀴논링은 세포에서 에너지를 생성하기 위한 매우 중요한 기능을 가지고 있다. CoQ10은 피부에서 항산화제로서 연구되어 왔으며, 최근 외용제로써 노화억제와 주름개선작용에 대해 보고된 바 있다. 이런 보고들은CoQ10이 항산화제로서 산화-환원작용을 통해 피부의 방어기능에 중요한 역할을 한다는 점을 시사하며, 일반적으로 산화-환원작용은 피부에서 흑화과정의 조절에도 많은 영향을 미친다. 따라서 본 연구자들은 CoQ10 이 피부의 색소조절기능이 있는지 알아보고자 하였다. 인체 정상 색소세포에CoQ10을 0.05-0.5 mM 처리한 결과 0.5, 0.25mM에서 멜라닌의 생합성을 약 50% 저해하였으며 이는 알려진 미백제인 Kojic acid나 vitamin C와 유사한 수준이었다. 또한, CoQ10은 인체 정상 색소세포에서 자외선이나 세포내 cAMP 증가 유도물질에 의한 멜라닌 생성을 억제하였다. 그러나 tyrosinase inhibitor인 kojic acid와는 달리, in vitro tyrosine hydroxylase의 억제효과는 보이지 않았다. CoQ10을 자외선으로 tanning을 유도시킨 brown guinea pig에 4주간 도포하고 육안 및 chromameter를 이용하여 미백효과를 측정한 결과, vehicle처리군에 비해 미백효과가 있음을 확인할 수 있었다. 이상의 결과에서 coenzyme Q10 은 in vitro및 in vivo에서 미백효과를 지닌 물질임을 확인할 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.87-94
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• 2021

Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation. Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+]i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at -60 mV and ORAI1 current by 97% ± 1% at -120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.282-289
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• 2018

Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiation-induced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the RNAxs program. Then we selected 34 siRNA sequences with ${\Delta}G{\geq}-34.6kcal/mol$, i-Score value ${\geq}65$, and siRNA scales score ${\leq}30$. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3' overhang at the 3' end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms.

• 대한화장품학회지
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• 제37권3호
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• pp.211-218
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• 2011

Glycogen synthase kinase 3 beta (GSK3${\beta}$)의 선택적 저해제인 Kenpaullone가 B16 멜라노마 및 사람의 멜라노사이트에 미치는 멜라닌 합성능을 조사하였다. Kepaullone은 B16 멜라노마 및 사람의 멜라노사이트에 대하여 세포증식에는 영향이 없는 범위 내에서 농도 의존적으로 멜라닌 합성을 촉진시켰다. B16 멜라노마 세포에 Kenpaullone을 첨가 48 h 후 tyrosinase 활성이 증가하였으며, 농도별 처리에 대하여 tyrosinase 단백질의 발현 및 tyrosinase mRNA양이 증가함을 관찰하였다. 결론적으로 Kenpaullone는 B16 멜라노마 세포에서 tyrosinase 효소의 발현을 증가시켜 멜라닌 합성을 촉진하는 것으로 판단되어진다. 따라서 GSK3${\beta}$ 저해제가 멜라닌 합성을 촉진시키는 결과는 백반증과 같은 저색소관련 질병의 치료제 개발의 가능성을 갖고 있는 소재로서 응용가능하리라고 판단되어진다.

• Journal of Photoscience
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• 제9권2호
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• pp.209-212
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• 2002

Cutaneous hyperpigmentation is a well-known consequence of both acute and chronic X-irradiation, although the molecular mechanisms involved are not well understood. Recently, protein kinase C-$\beta$ (PKC-$\beta$) was shown to activate tyrosinase, a key and the rate-limiting enzyme in melanogenesis [1]. In this study, we have investigated its role in mediating ionizing radiation-induced pigmentation by exposing cultured human melanocytes to X-irradiation. Increased tyrosinase activity after the 4 Gys exposure was observed within 48 hrs and total melanin content doubled after 7 days. Interestingly, tyrosinase mRNA level was not affected by X-irradiation. However, there was a 2-3 fold increase in PKC-$\beta$ mRNA after 48 hours of irradiation, coinciding with the increase in tyrosinase activity. This induction was not due to non-specific heat generated during the irradiation because when melanocytes were incubated at 4$0^{\circ}C$, there was no induction of PKC-$\beta$ mRNA. Taken together, these data suggest that X-irradiation induces cutaneous hyperpigmentation, at least in part, by up-regulating the level of PKC-$\beta$.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.268-284
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• 2003

Nor-aporphine derivatives have been discovered which interfere with the flux of Calcium into and out of the cell interior. It has been shown that adrenergic antagonists that block the Calcium exchange lead to an inhibition of Protein kinase C activity, thus blocking tyrosinase activation. Di-acetyl-dimethoxy-methyl-nor-aporphine is a semi-synthetic molecule of natural origin with very high potency. On B16 melanocytes as well as in normal human melanocytes the decrease in melanin synthesis reaches -50％ at a level of 40 ppm in the culture medium. On a molar concentration basis, this is 50 to 70 times stronger than Kojic acid inhibition. Yet, the cell viability is not affected. Reversibility studies show that after washing out of the active compound, melanogenesis returns to normal levels. Possible mechanisms of the activity are discussed. Tests carried out on SkinEthic(R) three-dimensional models of the epidermis and in vivo clinical studies on Asian population confirm the strong inhibition of melanogenesis. Safety evaluation of these molecules, on the other hand, demonstrates good skin tolerance and absence of toxicity.

• Obstetrics & gynecology science
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• 제61권6호
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• pp.698-701
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• 2018

We report a rare case of vaginal amelanotic melanoma. Malignant melanomas are cutaneous and extracutaneous tumors that arise from embryological remnants of neural crest cells/melanocytes. Amelanotic melanomas at such rare locations can be misdiagnosed both clinically and radiologically. Therefore, histopathological examination and immunohistochemistry are mandatory for the diagnosis of these tumors. We diagnosed this case using histopathology and confirmed the diagnosis based on the presence of immunohistochemical markers human melanoma black 45 (HMB45) and S-100.