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Elucidation of the mechanism of action and the target molecules of ingredients in crude extracts by chemical genetics approach using yeast knock-out strain collection

Research Project

Project/Area Number 19K07145
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47050:Environmental and natural pharmaceutical resources-related
Research InstitutionNagasaki International University

Principal Investigator

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

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsケミカルジェネティクス / 出芽酵母 / 生薬エキス / カンゾウ / オウレン / オウゴン / 相互作用 / グリチルリチン酸 / 作用機序 / 標的分子 / 甘草 / 黄連
Outline of Research at the Start

生薬エキスは多種多様な成分からなる多成分系薬物であり、エキス全体としての薬理作用と、個々の含有成分の作用機序や成分間の相乗効果との因果関係は解明されていない部分が多い。本研究では、ケミカルジェネティクス的手法により約4000株の遺伝子破壊出芽酵母株を用いることで、数種の代表的な生薬エキスに対する感受性株を見つけ、その変動パターンを解析し比較する。それによりエキス中に存在する個々の成分が、標的分子群にどのように作用するのかを明確にする。さらに、エキス中における生薬成分の真の標的分子および成分間の相乗効果の解明を行うことで、生薬・漢方製剤の新たな科学的エビデンス提供に貢献することを目指す。

Outline of Final Research Achievements

In this study, we used the chemical genetics approach using approximately 4000 yeast knock-out strain collection to identify the mechanism of action and the target molecules of ingredients in crude extracts, including Glycyrrhiza (Licorice), Coptis rhizome, Scutellaria root. Analyses of their variation patterns demonstrated that these crude drug extracts acted on genes and pathways different from those of representative drugs and chemicals. Furthermore, the functions and subcellular localization of the genes of the sensitive strains were diverse and specific, depending on each crude drug extract.

Academic Significance and Societal Importance of the Research Achievements

本研究は、ケミカルジェネティクス的手法を用いて生薬エキスが約4000の遺伝子群に与える影響を網羅的に解析する初の試みである。本研究により、生薬エキスにより与える遺伝子群は複雑かつ多岐にわたるとともに、一部では共通する部分も見られた。今後、より詳細な検討を要するが、本研究が、生薬・漢方エキスなどの多成分系薬物の作用機序解明の一助になり得ると考える。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (11 results)

All 2023 2022 2021 2020 2019 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Development of an indirect competitive enzyme-linked immunosorbent assay for formononetin and its application in a cell-based assay using MC3T3-E1 cells2023

    • Author(s)
      Fujii Shunsuke、Ohta Tomoe、Ehama Riho、Irikida Mizuki、Nomura Shuichi、Shoyama Yukihiro、Uto Takuhiro
    • Journal Title

      Food Chemistry

      Volume: 403 Pages: 134339-134339

    • DOI

      10.1016/j.foodchem.2022.134339

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Highly Sensitive Chemiluminescence Enzyme Immunostaining Assay to Determine Glycyrrhizin Content Using Anti-glycyrrhizin Monoclonal Antibody2022

    • Author(s)
      Fujii Shunsuke、Shoyama Yukihiro、Nomura Shuichi、Uto Takuhiro
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 70 Issue: 10 Pages: 694-698

    • DOI

      10.1248/cpb.c22-00405

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2022-10-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunological Separation of Bioactive Natural Compounds from Crude Drug Extract and Its Application for Cell-Based Studies2021

    • Author(s)
      Uto Takuhiro、Ohta Tomoe、Fujii Shunsuke、Shoyama Yukihiro
    • Journal Title

      Antibodies

      Volume: 10 Issue: 4 Pages: 48-48

    • DOI

      10.3390/antib10040048

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Applications of Monoclonal Antibodies Against Natural Compounds for Functional Analysis of Crude Drugs2020

    • Author(s)
      Takuhiro Uto, Shunsuke Fujii, Seiichi Sakamoto, Tomoe Ohta, Yukihiro Shoyama
    • Journal Title

      Current Pharmacology Reports

      Volume: 6 Issue: 4 Pages: 192-201

    • DOI

      10.1007/s40495-020-00224-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] アルクチゲニンおよびアルクチインに対するモノクローナル抗体を用いた間接競合ELISAの確立2023

    • Author(s)
      藤井俊輔、太田智絵、友利桃子、小嶋涼華、野村秀一、宇都 拓洋
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] シャルコー・マリー・トゥース病治療薬を志向したベルベリン類縁化合物の構造活性相関研究2023

    • Author(s)
      宮本怜奈、永松愛美、牛之濱早紀、太田智絵、原太一、宇都 拓洋
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ホルモノネチンに対する特異的モノクローナル抗体の作製および間接競合ELISAへの応用2022

    • Author(s)
      藤井俊輔、太田智絵、正山征洋、宇都拓洋
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 甘草エキスに含まれるミトコンドリア機能改善成分の探索2020

    • Author(s)
      佐藤美沙希,石橋優美子,髙崎伸也,宇都拓洋,太田一寿
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Analysis of synergistic effects and molecular targets of natural compounds using monoclonal antibodies against natural compounds2019

    • Author(s)
      Takuhiro Uto
    • Organizer
      7th International Conference on Food Factors (ICoFF2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 長崎国際大学 薬品資源学研究室HP 研究業績

    • URL

      http://niu.pharmacog.jp/achievement03.html

    • Related Report
      2022 Annual Research Report 2021 Research-status Report 2020 Research-status Report 2019 Research-status Report
  • [Remarks] 長崎国際大学 教員データベース

    • URL

      https://www1.niu.ac.jp/about/teacher/detail.html?tid=230

    • Related Report
      2022 Annual Research Report 2021 Research-status Report 2020 Research-status Report 2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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