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Chemical elucidation of efficacy and safety of health functional food

Research Project

Project/Area Number 20K15486
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 38050:Food sciences-related
Research InstitutionShowa University

Principal Investigator

Mizuno Mirei  昭和大学, 薬学部, 講師 (60766195)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords機能性食品 / 活性酸素 / 抗酸化作用 / プロオキシダント効果 / 銅イオン / 抗酸化活性 / キノン / チモキノン / 鉄イオン / キレート / スーパーフード / サプリメント
Outline of Research at the Start

パラキノンは生体内のタンパクやDNAと容易に付加して毒性を示すことが知られている。一方、サプリメントやスーパーフードに含有しパラキノン骨格を有するCoQ10やチモキノンは、その有効性が謳われている。つまりパラキノンは「薬と毒薬」の二面性を持つことが懸念される。本研究ではパラキノン骨格を有する化合物の生理作用を化学的に解析し、ヒトへの有効性と安全性を評価することを目的とする。これらが有する抗酸化作用やDNA・タンパクへの影響を評価し、官能基や濃度など影響因子を推測することで、化合物の生体への影響を明らかにできる。

Outline of Final Research Achievements

Thymoquinone (TQ) is reduced to thymohydroquinone (THQ) through a reduction in the body. We predicted that THQ is the active form in the body. First, the antioxidant activity of TQ and THQ was evaluated, THQ was found to have stronger antioxidant activity than TQ. On the other hand, it was found that THQ generated copper-bound reactive oxygen species in the presence of Cu2+ to induce pro-oxidant effect. Next, the interaction between the compounds and copper was measured using an ultraviolet-visible spectrophotometer. The interaction between Cu2+ and THQ was confirmed. Furthermore, the tyrosinase inhibitory activity of the compounds was measured, THQ exhibited inhibitory effect. It could be demonstrated that THQ is the main form of each activity and has both toxicity and beneficial effects in the body.

Academic Significance and Societal Importance of the Research Achievements

パラキノン骨格を有するビタミンKやコエンザイムQ10(CoQ10)は、サプリメントとして広く流通している。ブラッククミンシード含有成分であるチモキノンもパラキノン骨格を有し、抗酸化活性や抗がん作用など多様な生理活性が報告されている。その一方でキノン系化合物が生体内で毒性を示す報告があり、これらは生体へ「薬」および「毒」の2つの作用を持つことが懸念される。サプリメントやスーパーフードは法律の規制が厳しくないため、消費者の判断で自由に服用が可能となり、条件次第では毒性を示す可能性がある。そのため、本研究で得られた知見を元に、正しい情報を消費者に発信することで健康被害を防ぐことが可能となる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (18 results)

All 2024 2023 2022 2021 2020

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (11 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Suppressive effect of resveratrol, catechin and their conformationally constrained analogs on neutrophil extracellular trap formation by HL-60-derived neutrophils2024

    • Author(s)
      Ohinata Hitomi、Phimarn Wiraphol、Mizuno Mirei、Obama Takashi、Fukuhara Kiyoshi、Makiyama Tomohiko、Watanabe Yuichi、Itabe Hiroyuki
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 75 Issue: 1 Pages: 17-23

    • DOI

      10.3164/jcbn.23-80

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Planar catechin increases bone mass by regulating differentiation of osteoclasts in mice2024

    • Author(s)
      Daiki Sugawara, Nobuhiro Sakai, Yurie Sato, Yuki Azetsu, Akiko Karakawa, Masahiro Chatani, Mirei Mizuno, Yasubumi Maruoka, Mie Myers, Kiyoshi Fukuhara, Masamichi Takami
    • Journal Title

      J Oral Biosci.

      Volume: - Issue: 1 Pages: 196-204

    • DOI

      10.1016/j.job.2024.01.009

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DTPA-Bound Planar Catechin with Potent Antioxidant Activity Triggered by Fe3+ Coordination2023

    • Author(s)
      Fukuhara Kiyoshi、Nakanishi Ikuo、Imai Kohei、Mizuno Mirei、Matsumoto Ken-ichiro、Ohno Akiko
    • Journal Title

      Antioxidants

      Volume: 12 Issue: 2 Pages: 225-225

    • DOI

      10.3390/antiox12020225

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antioxidant and Prooxidant Effects of Thymoquinone and Its Hydroquinone Metabolite2022

    • Author(s)
      M. Mizuno, K. Fukuhara
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 45 Issue: 9 Pages: 1389-1393

    • DOI

      10.1248/bpb.b22-00199

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2022-09-01
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of natural antioxidant derivatives in the treatment and prevention of lifestyle-related diseases2021

    • Author(s)
      福原 潔、水野 美麗
    • Journal Title

      Journal of The Showa University Society

      Volume: 81 Issue: 5 Pages: 402-413

    • DOI

      10.14930/jshowaunivsoc.81.402

    • NAID

      130008142377

    • ISSN
      2187-719X, 2188-529X
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transfer and enzyme-mediated metabolism of oxidized phosphatidylcholine and lysophosphatidylcholine between low- and high-density lipoproteins.2020

    • Author(s)
      Naoko Sawada, Takashi Obama, Mirei Mizuno, Kiyoshi Fukuhara, Sanju Iwamoto, Toshihiro Aiuchi, Tomohiko Makiyama and Hiroyuki Itabe
    • Journal Title

      Antioxidants

      Volume: 9 Issue: 11 Pages: 1045-1045

    • DOI

      10.3390/antiox9111045

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design, Synthesis, and Biological Activity of Conformationally Restricted Analogues of Silibinin2020

    • Author(s)
      Mizuno Mirei、Mori Kazunori、Tsuchiya Keisuke、Takaki Takashi、Misawa Takashi、Demizu Yosuke、Shibanuma Motoko、Fukuhara Kiyoshi
    • Journal Title

      ACS Omega

      Volume: 5 Issue: 36 Pages: 23164-23174

    • DOI

      10.1021/acsomega.0c02936

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] α-グルコシダーゼを創薬標的とした新規フラボノイド誘導体の開発2024

    • Author(s)
      水野美麗、福原潔
    • Organizer
      日本農芸化学会2024年度大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] アミロイドβの神経毒性を抑制する新規ペプチドの開発2023

    • Author(s)
      福原潔、沖山佳生、三澤隆史、水野美麗、出水庸介、柴沼質子、大野彰子
    • Organizer
      第36回日本酸化ストレス学会関東支部会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 平面型カテキン[planar catechin:PCat]の骨量増加作用2023

    • Author(s)
      菅原大貴、高見正道、畔津祐季、唐川亜希子、茶谷昌宏、水野美麗、福原潔、 坂井信裕
    • Organizer
      第8回日本骨免疫学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Aβを創薬標的とした新規カテキン-カプサイシン誘導体の開発2023

    • Author(s)
      水野美麗、福原潔
    • Organizer
      日本農芸化学会2023年度大会
    • Related Report
      2022 Research-status Report
  • [Presentation] キノン構造を有する機能性化合物の抗酸化作用とプロオキシダント効果2022

    • Author(s)
      水野美麗、福原潔
    • Organizer
      日本農芸化学会2022年度大会
    • Related Report
      2022 Research-status Report 2021 Research-status Report
  • [Presentation] アミロイドβの神経毒性を抑制する新規ペプチドの開発2022

    • Author(s)
      福原潔、森一憲、沖山佳生、三澤隆史、水野美麗、出水庸介、柴沼質子、大野彰子
    • Organizer
      日本農芸化学会2022年度大会
    • Related Report
      2022 Research-status Report
  • [Presentation] アミロイドβの神経毒性を抑制する新規ペプチドの開発2022

    • Author(s)
      福原 潔、森 一憲、沖山 佳生、三澤 隆史、水野 美麗、出水 庸介、柴沼 質子、大野 彰子
    • Organizer
      日本農芸化学会2022年度大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Functional improvement of silibinin analogues with constrained 3D structures2021

    • Author(s)
      M. Mizuno, K. Mori, K. Tsuchiya, M. Shibanuma, K. Fukuhara
    • Organizer
      13th AMFC International Medicinal Chemistry symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Rationally designed peptide modulators of amyloid-β toxicity in Alzheimer’s disease2021

    • Author(s)
      Kiyoshi Fukuhara, Kazunori Mori, Yoshio Okiyama, Takashi Misawa, Mirei Mizuno, Yosuke Demizu, Motoko Shibanuma, Akiko Ohno
    • Organizer
      13th AMFC International Medicinal Chemistry symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] シリビニンの高機能化を目指した創薬研究2021

    • Author(s)
      水野 美麗
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Research-status Report
  • [Presentation] C-メチルフィセチンのラジカル消去活性2021

    • Author(s)
      福原 潔
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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