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Studies on the molecular mechanisms of the effects of ingested phytochemicals on the reactive oxygen species-generating system of cells in the intestinal tract

Research Project

Project/Area Number 19K02329
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 08030:Family and consumer sciences, and culture and living-related
Research InstitutionShokei Junior College

Principal Investigator

Kikuchi Hidehiko  尚絅大学短期大学部, その他部局等, 教授 (10301384)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsフィトケミカル / 腸管細胞 / マクロファージ / 活性酸素 / 自然免疫 / Nox2 / ウロリチンA / L-テアニン / 腸管 / スーパーオキシド / 白血球分化 / 3',4'-ジヒドロキシフラボン / エラグ酸 / 腸内細菌 / 活性酸素産生系 / 分化誘導 / 遺伝子発現 / カルコン / スルフォラファン / エクオール / 食品成分
Outline of Research at the Start

食生活は健康維持・増進の観点から非常に高い関心を集めている。活性酸素はその発生が食生活とも深く関わり、老化や発癌の原因の一つとして健康維持・増進に強い影響を及ぼす最重要因子の一つである。活性酸素は無秩序に発生した場合には生体に大きな害を及ぼす一方で、発生する時間、量及び場所が適切に制御されている場合には殺菌剤や情報伝達物質等、有用な物質として機能しうる。本研究課題では、食物の摂取(摂食)と活性酸素産生の関わりという観点から、摂取した食品成分やその誘導体(代謝物等)によって腸管に存在する活性酸素産生細胞の活性酸素産生系が受ける影響とその機序について、網羅的・総合的に解析する。

Outline of Final Research Achievements

In this study, I mainly focused on the macrophage Nox2 (gp91-phox) as a superoxide-generating system of cells in the intestinal tract. Retinoic acid induces differentiation of human monoblast U937 cells to macrophage-like cells, which induces superoxide-generating ability. To know the effects of phytochemicals on the retinoic acid-induced superoxide-generating ability, U937 cells were grown with retinoic acid in the presence or absence of various phytochemicals. As a result, chalcones, sulforaphane, urolithin A, 3', 4'-dihydroxyflavones and L-theanine enhanced the gene expression of gp91-phox, resulting in up-regulation of the retinoic acid-induced superoxide-generating ability of U937 cells. These data suggested that these phytochemicals can bring about enhancement of the superoxide-generating ability of leukocytes, resulting in up-regulation of innate immune response.

Academic Significance and Societal Importance of the Research Achievements

食品中に含まれる植物性生理活性物質(フィトケミカル)は多彩な生物活性を有し、疾病の予防や治療を通じて人間の健康維持に寄与することが期待されている。本研究では、食品成分と直接接する機会が多い消化管の中で活性酸素産生能を有する腸管細胞、特にマクロファージに着目して、フィトケミカルがマクロファージの活性酸素産生能に及ぼす影響を解析した。その結果、カルコン類、スルフォラファン、ウロリチンA、3',4'-ジヒドロキシフラボンやL-テアニンがマクロファージの活性酸素産生能を亢進することが明らかとなった。これらの研究成果は、上記フィトケミカルが免疫力(自然免疫)を増強する可能性を強く示唆するものである。

Report

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

    (18 results)

All 2022 2021 2020 2019 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (1 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Potential role of green tea amino acid L-theanine in activation of innate immune response via enhancing expression of cytochrome b 558 responsible for the reactive oxygen species-generating ability of leukocytes2022

    • Author(s)
      Hidehiko Kikuchi, Kaori Harata, Sumiko Akiyoshi, Takefumi Sagara, Harishkumar Madhyastha, Futoshi Kuribayashi
    • Journal Title

      Microbiology and Immunology

      Volume: - Issue: 6 Pages: 342-349

    • DOI

      10.1111/1348-0421.12977

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 3’, 4’-Dihydroxyflavone enhances all-<i>trans</i> retinoic acid-induced superoxide-generating activity through up-regulating transcription of gp91-phox in human monoblastic U937 cells, as opposed to flavone and other hydroxyflavone derivatives2021

    • Author(s)
      Hidehiko Kikuchi, Kaori Harata, Sumiko Akiyoshi, Harishkumar Madhyastha, Futoshi Kuribayashi
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 8 Issue: 2 Pages: 53-59

    • DOI

      10.2131/fts.8.53

    • NAID

      130008044474

    • ISSN
      2189-115X
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ellagic acid and its fermentative derivative urolithin A show reverse effects on the gp91-phox gene expression, resulting in opposite alterations in all-trans retinoic acid-induced superoxide generating activity of U937 cells2021

    • Author(s)
      Hidehiko Kikuchi, Kaori Harata, Harishkumar Madhyastha, Futoshi Kuribayashi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 25 Pages: 100891-100891

    • DOI

      10.1016/j.bbrep.2020.100891

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptional profiles of histone acetyltransferases in human monoblast U937 cells treated with all-trans retinoic acid or 1α,25-dihydroxyvitamin D32021

    • Author(s)
      Hidehiko Kikuchi, Yumi Nakagawa, Yui Hirayama, Kaori Harata
    • Journal Title

      Journal of Association of Food Science Education in Japan

      Volume: 12 Pages: 19-24

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possibility for nutritional improvement of the "authentic milk bread" by increasing the amount of milk added2021

    • Author(s)
      Aya Shibata, Sayaka Ichihara, Miwa Kubota, Aimi Sakata, Ayaka Shibata, Yuko Moriguchi, Kaori Harata, Takefumi Sagara, Hidehiko Kikuchi
    • Journal Title

      Journal of Association of Food Science Education in Japan

      Volume: 12 Pages: 25-30

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Retinoic acid dramatically enhances cytotoxicity of equol against human monoblastic U937 cells, but not against human peripheral neutrophils2020

    • Author(s)
      Hidehiko Kikuchi, Kaori Harata, Chikage Kawai, Harishkumar Madhyastha, Akira Yamauchi, Futoshi Kuribayashi
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 7 Issue: 4 Pages: 201-206

    • DOI

      10.2131/fts.7.201

    • NAID

      130007847965

    • ISSN
      2189-115X
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production and evaluation of the authentic milk bread using a lactose-utilizing yeast, Kluyveromyces marxianus2020

    • Author(s)
      Aya Shibata, Kaori Harata, Yuko Moriguchi, Risako Kanegawa, Ayaka Nagahira, Misaki Shigematsu, Yuri Takamura, Haruno Watanabe, Takefumi Sagara, Harishkumar Madhyastha, Hidehiko Kikuchi
    • Journal Title

      Current Topics in Biotechnology

      Volume: 11 Pages: 31-36

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sulforaphane shows remarkable growth inhibition and cytotoxicity against several human leukemia cell lines2020

    • Author(s)
      Akiyoshi Sumiko, Kikuchi Hidehiko, Minami Hisanori
    • Journal Title

      Journal of Association of Food Science Education in Japan

      Volume: 11 Pages: 1-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sulforaphane shows growth inhibitory effects against Escherichia coli and Bacillus subtilis via reactive oxygen species production2020

    • Author(s)
      Tsuruta Chigusa, Mimura Akari, Harata Kaori, Kikuchi Hidehiko
    • Journal Title

      Journal of Association of Food Science Education in Japan

      Volume: 11 Pages: 9-12

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chalcone skeleton promotes transcription of gp91-phox gene but inhibits expression of gp91-phox protein, and hydroxyl groups in hydroxychalcones participate in the stable expression of gp91-phox protein.2019

    • Author(s)
      Kikuchi H, Mimuro H, Madhyastha H, Kuribayashi F.
    • Journal Title

      Microbiology and Immunology

      Volume: 63 Issue: 10 Pages: 438-443

    • DOI

      10.1111/1348-0421.12732

    • NAID

      40022036987

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sulforaphane displays the growth inhibition, cytotoxicity and enhancement of retinoic acid-induced superoxide-generating activity in human monoblastic U937 cells2019

    • Author(s)
      Akiyoshi Sumiko, Kikuchi Hidehiko, Kuribayashi Futoshi, Madhyastha Harishkumar, Minami Hisanori
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 6 Issue: 8 Pages: 319-325

    • DOI

      10.2131/fts.6.319

    • NAID

      130007760707

    • ISSN
      2189-115X
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functions of B cell development-related transcription factors systematically revealed in immature B cells by gene targeting techniques using chicken DT40 cells2019

    • Author(s)
      Kikuchi Hidehiko, Kuribayashi Futoshi, Nakayama Masami, Nakayama Tatso
    • Journal Title

      Current Topics in Biochemical Research

      Volume: 20 Pages: 43-52

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒドロキシカルコンの水酸基の数と位置がヒト白血病細胞U937に対する細胞毒性を決定する。2019

    • Author(s)
      菊池秀彦、栗林太
    • Organizer
      第42回日本分子生物学会年回
    • Related Report
      2019 Research-status Report
  • [Remarks] 尚絅大学・尚絅大学短期大学部

    • URL

      https://www.shokei-gakuen.ac.jp/univ/

    • Related Report
      2021 Annual Research Report
  • [Remarks] KIKUCHI-LAB

    • URL

      https://kikuchi-biolchem.jimdo.com

    • Related Report
      2021 Annual Research Report
  • [Remarks] KIKUCHI LAB.

    • URL

      https://kikuchi-biolchem.jimdofree.com/

    • Related Report
      2020 Research-status Report
  • [Remarks] kikuchi-biolchem

    • URL

      https://kikuchi-biolchem.jimdofree.com

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] パン、パン生地およびパンの製造方法2020

    • Inventor(s)
      菊池秀彦、相良剛史、原田香、柴田文
    • Industrial Property Rights Holder
      菊池秀彦、相良剛史、原田香、柴田文
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-099640
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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

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