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Depigmenting Effects of Mistletoe (Viscum album var. coloratum) Extracts

겨우살이 추출물의 미백 효과

  • Hah, Young-Sool (Biomedical Research Institute, Gyeongsang National University Hospital) ;
  • Kim, Eun-Ji (Biomedical Research Institute, Gyeongsang National University Hospital) ;
  • Goo, Young Min (Anti-Aging Research Group, Gyeongnam Oriental Anti-Aging Institute) ;
  • Kil, Young Sook (Anti-Aging Research Group, Gyeongnam Oriental Anti-Aging Institute) ;
  • Sin, Seung Mi (Anti-Aging Research Group, Gyeongnam Oriental Anti-Aging Institute) ;
  • Kim, Sang Gon (Anti-Aging Research Group, Gyeongnam Oriental Anti-Aging Institute) ;
  • Kang, Ha Eun (Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital) ;
  • Yoon, Tae-Jin (Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital)
  • 하영술 (경상국립대학교병원 의생명연구원) ;
  • 김은지 (경상국립대학교병원 의생명연구원) ;
  • 구영민 ((재)경남한방항노화연구원) ;
  • 길영숙 ((재)경남한방항노화연구원) ;
  • 신승미 ((재)경남한방항노화연구원) ;
  • 김상곤 ((재)경남한방항노화연구원) ;
  • 강하은 (경상국립대학교 의과대학 피부과학교실 건강과학연구원 경상국립대학교병원) ;
  • 윤태진 (경상국립대학교 의과대학 피부과학교실 건강과학연구원 경상국립대학교병원)
  • Received : 2022.02.15
  • Accepted : 2022.04.20
  • Published : 2022.05.30

Abstract

Melanin pigments are the main cause of skin color. They are produced in melanocytes and then transferred to keratinocytes, which eventually gives the skin surface a variety of colors. Although many skin-lightening or depigmenting agents have been developed, the demand for materials to reduce pig- mentation is still increasing. Here, we tried to find materials for skin-lightening or depigmentation using natural compounds and found that mistletoe (Viscum album var. coloratum) extracts (ME) had an inhibitory effect on tyrosinase activity. As a result, ME significantly reduced pigmentation in human primary melanocytes. In addition, a promoter reporter assay revealed that ME inhibited the transcription of microphthalmia-associated transcription factor (MITF), melanophilin (MLPH), tyrosinase-related protein-2 (TRP-2), and tyrosinase (TYR) genes in HM3KO melanoma cells. In addition, ME decreased the protein level for pigmentation-related molecules, such as TYR and TRP-1. Furthermore, it markedly inhibited the melanogenesis of zebrafish embryos, an in vivo evaluation model for pigmentation. To elucidate the action mechanism of ME, we investigated its effects on intracellular signaling. Eventually, the ME dramatically decreased the phosphorylation of the cAMP responsive element binding protein (CREB), AKT, and ERK. The data suggest that ME may inhibit the melanogenesis pathway by regulating the signaling pathway related to pigmentation. Taken together, these data propose that ME can be developed as a depigmenting or skin-lightening agent.

멜라닌 색소는 피부색의 주요 원인이다. 멜라닌 색소는 멜라닌 세포에서 생성된 다음 각질 세포로 전달되어 결국 피부 표면에 다양한 색상을 부여한다. 많은 탈색제 및 피부 미백제가 개발되었지만, 색소 침착을 감소시키기 위한 재료에 대한 수요는 여전히 증가하고 있다. 본 연구에서 천연 화합물을 사용하여 탈색 및 피부 미백에 대한 재료를 찾으려고 시도한 결과 겨우살이(Viscum album var. coloratum) 추출물이 색소 침착을 억제할 수 있음을 발견하였다. 인간 멜라닌 세포에 겨우살이 추출물(mistletoe extracts, ME)을 처리했을 때 색소 침착이 극적으로 감소하였다. 프로모터 리포터 분석은 ME 처리가 HM3KO 흑색종 세포에서 microphthalmia-associated transcription factor (MITF), melanophilin (MLPH), tyrosinase related protein 2 (TRP-2), and tyrosinase (TYR) 유전자의 전사를 억제한다는 것을 보여주었다. 일관되게 ME는 MITF, TRP-1 및 TYR과 같은 색소 침착 관련 분자의 단백질 수준을 감소시켰다. 또한 ME는 cAMP Responsive Element Binding Protein (CREB), AKT 및 ERK의 인산화를 감소시켰다. 이러한 결과는 ME가 색소 침착과 관련된 세포 내 신호 전달의 조절을 통해 멜라닌 생성을 억제한다는 것을 시사한다. 끝으로 ME는 색소 침착에 대한 생체 내 평가 모델인 제브라피쉬 배아의 멜라닌 생성을 현저하게 억제하였다.

Keywords

Acknowledgement

본 연구는 (재)경남한방항노화연구원 연구사업(연구개발과제명: 피부 미백 유용성분 발굴 및 기존 허가 의약품 활용한 색소 조절 약물 발굴)의 지원에 의해 이루어진 연구이며 지원에 감사드립니다.

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