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Discovery of natural compounds for the treatment of vitiligo and elucidation of their mechanism of action

Research Project

Project/Area Number 16K18905
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Natural medicines
Research InstitutionNagasaki International University

Principal Investigator

UTO Takuhiro  長崎国際大学, 薬学部, 准教授 (90469396)

Research Collaborator SHOYAMA yukihiro  
OHTA tomoe  
FUJII shunsuke  
NGUYEN huu tung  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords白斑 / メラニン / 生薬 / スクリーニング / 甘草フラボノイド / 辛夷 / マグノリン / シリビニン / メラニン合成促進 / 作用機序 / 甘草 / 丁子 / 白斑治療 / メラニン合成促進物質 / 作用機序解析 / (+)-magnolin / 標的分子 / 薬学 / 天然資源系薬学
Outline of Final Research Achievements

The aim of this study was to screen 130 crude drugs and 250 natural compounds to identify novel compounds to induce melanin synthesis in melanoma cell lines. We found that liquiritin and liquiritigenin, major flavonoids in licorice root, induced melanin synthesis via activation of the p38 and PKA signaling pathways. Among the 130 crude extracts, Magnolia flower extract strongly activated melanogenesis, and we identified (+)-magnolin from its ethyl acetate fraction as the active compound leading to melanin synthesis. Moreover, analysis using a three-dimensional epidermal model revealed that the ethyl acetate fraction and (+)-magnolin induced melanin synthesis through the epidermal barrier. Among the 250 natural compounds, silibinin, the main compound extracted from the milk thistle (Silybum marianum), evoked melanin synthesis. Our findings will be valuable in providing leads for the discovery of new drugs for the treatment of vitiligo.

Academic Significance and Societal Importance of the Research Achievements

近年、メラニン合成促進作用を示す天然物は報告されてはいるが、網羅的なスクリーニングを行った研究はなく、またメラニン合成促進活性を有する化合物の詳細な分子作用機序や標的分子の解明、ヒト皮膚3次元モデルや動物レベルでの効果の立証まで至っているものは限られていた。本研究は、これらを解決する先駆的研究であり、本研究で得られた成果は、将来新しい白斑治療薬創出に貢献することが期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 Other

All Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Presentation] マリアアザミ種子成分シリビニンのメラニン合成促進活性とその分子機構解明2018

    • Author(s)
      片山幸樹、Bua Siritantiwat、宮嶋 祥吾、太田 智絵、正山 征洋、宇都 拓洋
    • Organizer
      第2回食薬ヘルスイノベーション研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] シリビニンのメラニン合成誘導能とその作用機序解析2018

    • Author(s)
      片山幸樹、Bua Siritantiwat、宮嶋祥吾、太田智絵、宇都拓洋、正山征洋
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 辛夷から単離した(+)-Magnolinのメラニン合成誘導能とその作用機序解析2017

    • Author(s)
      宇都拓洋、太田智絵、Nguyen Huu Tung、Kasina Soitanasirikul、久住呂美和、正山征洋
    • Organizer
      日本生薬学会第64回年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 白斑治療薬開発を目指した天然由来メラニン合成促進物質の探索および作用機序に関する研究(学術奨励賞受賞講演)2017

    • Author(s)
      宇都拓洋
    • Organizer
      日本生薬学会第64回年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Magnolin isolated form Magnolia flower activates melanogenesis; Involvement of p38 and PKA signaling pathways2017

    • Author(s)
      Takuhiro Uto, Tomoe Ohta, Yukihiro Shoyama
    • Organizer
      Food for Health International Conference 2017 (FOHIC2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 長崎国際大学 薬学部 薬品資源学研究室 研究紹介

    • URL

      http://niu.pharmacog.jp/research.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 長崎国際大学 薬学部 薬品資源学研究室 研究紹介

    • URL

      http://niu.pharmacog.jp/index.html

    • Related Report
      2017 Research-status Report
  • [Remarks] 長崎国際大学 薬学部 薬品資源学研究室 研究紹介

    • URL

      http://niu.pharmacog.jp/research.html

    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] メラニン合成促進組成物2017

    • Inventor(s)
      正山征洋、宇都拓洋、太田智絵
    • Industrial Property Rights Holder
      正山征洋、宇都拓洋、太田智絵
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-149066
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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