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Development of natural products based on regulation of biological clock system

Research Project

Project/Area Number 19K07154
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 InstitutionIshikawa Prefectural Nursing University (2020-2021)
Aichi Gakuin University (2019)

Principal Investigator

Hirai Takao  石川県立看護大学, 看護学部, 教授 (80389072)

Co-Investigator(Kenkyū-buntansha) 中島 健一  愛知学院大学, 薬学部, 准教授 (70635135)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords時計遺伝子 / ベージュ脂肪細胞 / 天然物 / 生活習慣病
Outline of Research at the Start

健康長寿社会の実現に向けて、国民の健康寿命の延伸が必要不可欠である。本研究では、生物時計システムに着目し、分子レベルおよび個体レベルの両面から生物機能を制御する時計遺伝子の役割の一端を明らかにすると同時に、それら生物時計システムを標的とする天然資源由来の生活習慣病の予防・治療薬の開発を目指す。最終的には、生物時計システムを標的とした生活習慣病の予防・治療薬の創出と新しい治療理論の構築による健康長寿社会の実現に寄与することを目的とする。

Outline of Final Research Achievements

Recent studies indicated that circadian disruptions are associated with metabolic disorders. In this study, we aimed to identify natural products that modulate the transcriptional regulatory network of clock genes using crude herbal drugs frequently used for the preparation of Kampo prescriptions. First, we attempted to search for small molecules acting on ROR or Rev-erb based on the expression pattern of the BMAL1 promoter-driven luciferase gene. As a result, we found several crude drug extracts that decrease BMAL1 mRNA expression. In addition, analysis of the main active constituents of the extracts suggested that it may be involved in the regulation of cell differentiation in adipose progenitor. Furthermore, this study indicated that clock genes were involved in the expression of FGF21. Thus, these results may lead to the development of novel therapeutic agents based on chronopharmacology.

Academic Significance and Societal Importance of the Research Achievements

近年、生体時計は基本的生命現象だけでなく、病態解明や治療の標的として注目されている。本研究成果より、時計遺伝子の転写調節ネットワークを標的とする天然薬物の探索は肥満改善薬の創出に向けて有用である可能性が示唆された。また、時計遺伝子の転写調節ネットワークに作用する天然薬物の探索だけでなく、褐色脂肪細胞における時計遺伝子の新たな機能を見出した本研究成果は、時間薬理学に基づいた生活習慣病・老齢化疾患に対する新たな治療や予防法の開発、治療理論の構築に繋がると考えられる。

Report

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

    (9 results)

All 2022 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] Transmembrane G protein-coupled receptor 5 signaling stimulates fibroblast growth factor 21 expression concomitant with up-regulation of the transcription factor nuclear receptor Nr4a12021

    • Author(s)
      Kiyama Genki、Nakashima Ken-ichi、Shimada Kazumasa、Murono Naoko、Kakihana Wataru、Imai Hideki、Inoue Makoto、Hirai Takao
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 142 Pages: 112078-112078

    • DOI

      10.1016/j.biopha.2021.112078

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Naturally Occurring Compounds Regulating Brown/Beige Adipocyte Differentiation2019

    • Author(s)
      Hirai T, Takagi M, Nakashima KI, Inoue M
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 139 Issue: 6 Pages: 861-866

    • DOI

      10.1248/yakushi.18-00173-3

    • NAID

      130007657089

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2019-06-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Berberine stimulates fibroblast growth factor 21 by modulating the molecular clock component brain and muscle Arnt-like 1 in brown adipose tissue.2019

    • Author(s)
      Hirai T, Mitani Y, Kurumisawa K, Nomura K, Wang W, Nakashima KI, Inoue M
    • Journal Title

      Biochemical Pharmacology

      Volume: 164 Pages: 165-176

    • DOI

      10.1016/j.bcp.2019.04.017

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] G protein-coupled bile acid receptor TGR5 signaling regulates fibroblast growth factor 212022

    • Author(s)
      Takao Hirai, Hinako Hashimoto, Naoko Murono, Wataru Kakihana, Hideki Imai
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 老齢マウスを用いた加味四物湯のサルコペニア改善メカニズムの解析2020

    • Author(s)
      田中貴大,荒井哲也,平居貴生,井上誠
    • Organizer
      第37回和漢医薬学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] レンギョウによる代謝調節因子FGF21の発現促進作用に関する研究2020

    • Author(s)
      来山元規,平居貴生,嶋田一優,中島健一,井上 誠
    • Organizer
      第37回和漢医薬学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Fibroblast growth factor 21を制御する天然物の概日時計制御系への影響2019

    • Author(s)
      平居貴生、中島健一、井上 誠
    • Organizer
      第35回和漢医薬学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] New sesquiterpenoids from an endophytic fungus Paraconiothyrium brasiliense ECN2582019

    • Author(s)
      Ken-ichi Nakashima, Junko Tomida, Takao Hirai, Yoshiaki Kawamura, Makoto Inoue
    • Organizer
      67th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research
    • Related Report
      2019 Research-status Report
  • [Presentation] 植物内生真菌Paraconiothyrium brasilienseが産生する新規セスキテルペノイドに関する研究(2)2019

    • Author(s)
      中島健一、富田純子、平居貴生、河村好章、井上誠
    • Organizer
      日本生薬学会第65回年会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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