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Inhibition of Melanogenesis by Cucurbitacin B from Cucumis sativus L.

오이로부터 분리된 cucurbitacin B의 미백 효능 연구

  • Chang, Yun-Hee (Cosmetic Research & Development Center, LG Household & Healthcare Ltd.) ;
  • Choo, Jung-Ha (Cosmetic Research & Development Center, LG Household & Healthcare Ltd.) ;
  • Lee, So-Young (Cosmetic Research & Development Center, LG Household & Healthcare Ltd.) ;
  • Kim, Tae-Yoon (Cosmetic Research & Development Center, LG Household & Healthcare Ltd.) ;
  • Jin, Mu-Hyun (Cosmetic Research & Development Center, LG Household & Healthcare Ltd.) ;
  • Chang, Min-Youl (Cosmetic Research & Development Center, LG Household & Healthcare Ltd.) ;
  • Lee, Sang-Hwa (Cosmetic Research & Development Center, LG Household & Healthcare Ltd.) ;
  • Lee, Cheon-Koo (Cosmetic Research & Development Center, LG Household & Healthcare Ltd.) ;
  • Park, Sun-Gyoo (Cosmetic Research & Development Center, LG Household & Healthcare Ltd.)
  • 장윤희 (LG 생활건강 기술연구원 화장품 연구소) ;
  • 추정하 (LG 생활건강 기술연구원 화장품 연구소) ;
  • 이소영 (LG 생활건강 기술연구원 화장품 연구소) ;
  • 김태윤 (LG 생활건강 기술연구원 화장품 연구소) ;
  • 진무현 (LG 생활건강 기술연구원 화장품 연구소) ;
  • 장민열 (LG 생활건강 기술연구원 화장품 연구소) ;
  • 이상화 (LG 생활건강 기술연구원 화장품 연구소) ;
  • 이천구 (LG 생활건강 기술연구원 화장품 연구소) ;
  • 박선규 (LG 생활건강 기술연구원 화장품 연구소)
  • Received : 2014.11.09
  • Accepted : 2014.12.09
  • Published : 2014.12.31

Abstract

To develop an effective skin whitening agent for cosmetics, we isolated cucurbitacin B from Cucumis sativus L. which has been used as traditional skin lighting regimen by the bioactivity-guided fractionation, and investigated the inhibitory effects of cucurbitacin B on melanogenesis. At a non-cytotoxic concentration, cucurbitacin B reduced melanin contents of B16F1 melanoma cells in a dose-dependent manner. Cucurbitacin B did not directly inhibit mushroom tyrosinase activity, but it inhibited intracellular tyrosinase activity in a dose-dependent manner. Its inhibitory mechanism on melanin biosynthesis was further assessed, and we found that cucurbitacin B significantly decreased the protein level of tyrosinase, a major melanogenic enzymes and MITF, a master transcriptional factor of melanogenesis. In addition, cucurbitacin B increased the expression of WW domain-containing oxidoreductase (WWOX) which is known to function as tumor repressor and inhibits $Wnt/{\beta}$-catenin pathway. Collectively, these results suggest that cucuritacin B from C. sativus could be used as an active ingredient for skin whitening.

효능이 우수한 신규 미백 소재 개발을 위하여, 민간 및 전통 미백 처방에 사용되어 온 오이(Cucumis sativus L.)에서 활성 물질 분획 추적 연구를 통하여 cucurbitacin B를 분리 정제하고, cucurbitacin B의 멜라닌 합성에 미치는 효과를 B16F1 멜라노마 세포를 이용해 확인하였다. Cucurbitacin B는 세포 독성을 보이지 않는 농도에서 실험한 결과, 멜라닌 생합성을 농도 의존적으로 감소시켰다. Cucurbitacin B는 mushroom tyrosinase의 활성은 직접적으로 저해하지 않았지만, 세포에 처리했을 때 세포 내의 tyrosinase의 활성을 감소시킴을 확인하였다. 또한, cucurbitacin B의 이러한 멜라닌 합성 저해의 기전 연구를 위하여, 멜라닌 합성에 중요한 단백질인 tyrosinase와 microphthalmia-associated transcription factor (MITF)의 단백질 발현을 조사한 결과, cucurbitacin B가 tyrosinase와 MITF의 단백질의 발현을 농도 의존적으로 감소시키는 결과를 확인하였다. 또한, cucurbitacin B는 자외선에 의한 피부암 발생 억제인자(tumor repressor) 및 $Wnt/{\beta}$-catenin 신호전달 과정에 대한 억제 기능이 밝혀진 WW domain-containing oxidoreductase (WWOX)의 단백질 발현을 증가시킴을 추가적으로 확인하였다. 따라서, 이상의 연구 결과를 통해, 오이에서 분리 정제된 cucurbitacin B는 멜라닌 세포(melanocytes)에서 멜라닌 합성을 저해하는 효능이 있음을 확인하였으며, 향후 피부 미백 소재로 활용될 수 있을 것으로 판단된다.

Keywords

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